Clinical Trials List
Protocol NumberI4V-MC-JAHZ
NCT Number(ClinicalTrials.gov Identfier)NCT03616912
2018-11-01 - 2022-04-30
Phase III
Recruiting7
Terminated2
ICD-10M32
Systemic lupus erythematosus (SLE)
ICD-9710.0
Systemic lupus erythematosus
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients with Systemic Lupus Erythematosus
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Eli Lilly and Company
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 謝祖怡 Division of Rheumatology
- HSIN-HUA CHEN Division of Rheumatology
- 吳沂達 Division of Rheumatology
- 謝佳偉 Division of Rheumatology
- 林靖才 Division of Rheumatology
- Yi-Hsing Chen Division of Rheumatology
- 譚國棟 Division of Rheumatology
- 賴國隆 Division of Rheumatology
- 洪維廷 Division of Rheumatology
- 曾智偉 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 童建學 Division of Rheumatology
- 呂明錡 Division of Rheumatology
- 許寶寶 Division of Rheumatology
- 黃光永 Division of Rheumatology
- CHENG-HAN WU Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳英州 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林永章 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chen Der-Yuan 風濕免疫科
- Po-Hao Huang 風濕免疫科
- 黃建中 風濕免疫科
- 張詩欣 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Linkou Chang Gung Medical Foundation
Taiwan National PI
方耀凡
Co-Principal Investigator
- Ping-Han Tsai Division of Rheumatology
- TianMing Zhan Division of Rheumatology
- Shue-Fen Lo Division of Rheumatology
- 陳彥輔 Division of Rheumatology
- Chang-Fu Kuo Division of Rheumatology
- 張哲慈 Division of Rheumatology
The Actual Total Number of Participants Enrolled
3 Recruiting
Audit
None
Co-Principal Investigator
- 呂政勳 風濕免疫科
- KO-JEN LI 風濕免疫科
- CHIEH-YU SHEN 風濕免疫科
- 郭佑民 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Tzn-Min Lin 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Systemic Lupus Erythematosus
Objectives
Primary
To evaluate the long-term safety and tolerability of
baricitinib in patients with SLE.
Secondary
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD and background standard-of-care
therapy on SLE disease activity.
To evaluate the long-term corticosteroid sparing
effect of baricitinib 4-mg or 2-mg QD.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on SLE flares.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on mucocutaneous manifestations of
SLE.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on musculoskeletal manifestations of
SLE.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on individual organ system disease
activity.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on damage.
To evaluate the long-term effect of baricitinib 4-mg
or 2-mg QD on patient-reported outcomes (PROs).
Test Drug
Baricitinib
Active Ingredient
Baricitinib
Dosage Form
tablet
tablet
tablet
Dosage
2mg/tablet
4mg/tablet
4mg/tablet
Endpoints
Primary:
Safety and tolerability assessments will include:
Proportion of patients with treatment-emergent
adverse events (TEAEs), adverse events of special
interest (AESIs), and serious adverse events (SAEs).
Proportion of patients with temporary
investigational product interruptions and permanent
discontinuations.
Secondary:
Proportion of patients achieving SRI-4 response
through Week 156, defined as:
o Reduction of ≥4 points from baseline in
SLEDAI-2K score; and
o No new British Isles Lupus Assessment Group
(BILAG) A or no more than 1 new BILAG B
disease activity score; and
o No worsening (defined as an increase of ≥0.3
points [10 mm] from baseline) in the Physician’s
Global Assessment of Disease Activity.
Proportion of patients achieving an SRI-5, -6, -7, or
-8 response through Week 156.
Proportion of patients achieving an LLDAS
response through Week 156.
Change from baseline in mean total SLEDAI-2K
scores through Week 156.
Change from baseline in Physician’s Global Disease
Activity score through Week 156.
Change from baseline in prednisone dose through
Week 156.
Annualized mild/moderate flare rate.
Annualized severe flare rate.
Annualized flare rate (any severity).
Proportion of patients with CLASI total activity
score ≥10 at baseline with ≥50% reduction in
CLASI total activity score through Week 156.
Change from baseline in tender joint count through
Week 156.
Change from baseline in swollen joint count through
Week 156.
Proportion of patients with improvement in each
SLEDAI-2K organ system versus baseline through
Week 156.
Proportion of patients with worsening in each
SLEDAI-2K organ system versus baseline through
Week 156.
Change from baseline in SLICC/ACR damage index
total score through Week 156.
Change from baseline in Worst Pain NRS through
Week 156.
Change from baseline in Worst Joint Pain NRS
through Week 156.
Change from baseline in Worst Fatigue NRS
through Week 156.
Change from baseline in Patient Global Impression
of Severity through Week 156.
Change from baseline in mental component score
(MCS), physical component score (PCS), and
domain scores in the Short-Form 36-item health
survey version 2 (SF- 36v2) acute through Week
156.
Change from baseline in FACIT-F total score
through Week 156.
Change from baseline in the EQ-5D-5L through
Week 156.
Change from baseline in the WPAI-Lupus through
Week 156.
Safety and tolerability assessments will include:
Proportion of patients with treatment-emergent
adverse events (TEAEs), adverse events of special
interest (AESIs), and serious adverse events (SAEs).
Proportion of patients with temporary
investigational product interruptions and permanent
discontinuations.
Secondary:
Proportion of patients achieving SRI-4 response
through Week 156, defined as:
o Reduction of ≥4 points from baseline in
SLEDAI-2K score; and
o No new British Isles Lupus Assessment Group
(BILAG) A or no more than 1 new BILAG B
disease activity score; and
o No worsening (defined as an increase of ≥0.3
points [10 mm] from baseline) in the Physician’s
Global Assessment of Disease Activity.
Proportion of patients achieving an SRI-5, -6, -7, or
-8 response through Week 156.
Proportion of patients achieving an LLDAS
response through Week 156.
Change from baseline in mean total SLEDAI-2K
scores through Week 156.
Change from baseline in Physician’s Global Disease
Activity score through Week 156.
Change from baseline in prednisone dose through
Week 156.
Annualized mild/moderate flare rate.
Annualized severe flare rate.
Annualized flare rate (any severity).
Proportion of patients with CLASI total activity
score ≥10 at baseline with ≥50% reduction in
CLASI total activity score through Week 156.
Change from baseline in tender joint count through
Week 156.
Change from baseline in swollen joint count through
Week 156.
Proportion of patients with improvement in each
SLEDAI-2K organ system versus baseline through
Week 156.
Proportion of patients with worsening in each
SLEDAI-2K organ system versus baseline through
Week 156.
Change from baseline in SLICC/ACR damage index
total score through Week 156.
Change from baseline in Worst Pain NRS through
Week 156.
Change from baseline in Worst Joint Pain NRS
through Week 156.
Change from baseline in Worst Fatigue NRS
through Week 156.
Change from baseline in Patient Global Impression
of Severity through Week 156.
Change from baseline in mental component score
(MCS), physical component score (PCS), and
domain scores in the Short-Form 36-item health
survey version 2 (SF- 36v2) acute through Week
156.
Change from baseline in FACIT-F total score
through Week 156.
Change from baseline in the EQ-5D-5L through
Week 156.
Change from baseline in the WPAI-Lupus through
Week 156.
Inclution Criteria
[1] Are at least 20 years of age.
[2] Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
[3] Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 ACR criteria for classification of SLE prior to randomization.
[4] Have 1 or more of the following as assessed by the central lab during screening: a positive antinuclear antibody (ANA; titer ≥1:80), and/or a positive anti dsDNA, and/or a positive anti Smith (anti Sm). Patients with an ANA <1:80 at screening with documentation of a historical ANA ≥1:80 may be eligible, as assessed by the eligibility review committee.
Note: The ANA, anti dsDNA, and anti Smith measurements may be repeated by the central lab once during the screening period, and the value resulting from repeat testing may be accepted for enrollment eligibility if it meets the eligibility criterion.
[5] Have a total SLEDAI 2K score ≥6 during screening, with at least 4 points attributed to clinical items (not including items requiring laboratory value assessment). SLEDAI 2K items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
[6] Have a clinical SLEDAI 2K score ≥4 at Baseline (Visit 2); not including any items requiring laboratory value assessment.
[7] Have at least 1 BILAG A score or 2 BILAG B scores during the screening period. BILAG items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
Prior/Concomitant Therapy
[8] Are receiving at least one of the following SoC medications for SLE:
a. A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
b. A single immunosuppressant (such as methotrexate [MTX], azathioprine, mycophenolate, tacrolimus) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
c. An oral corticosteroid, initiated at least 4 weeks prior to screening (Visit 1), at a stable dose ≤ 40 mg/day prednisone (or equivalent) for at least 2 weeks prior to screening (Visit 1) and through baseline (Visit 2). If the patient is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥ 7.5 mg/day prednisone (or equivalent).
Patient Characteristics
[9] Male or nonpregnant, nonbreastfeeding female patient
a. Patients of child bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same sex relationship without sexual relationships with the opposite sex.
b. Total abstinence is defined as refraining from intercourse during the entirety of the study and for at least 1 week following the last dose of investigational product. Periodic abstinence such as calendar, ovulation, symptothermal, post ovulation methods and withdrawal are not acceptable methods of contraception.
c. Otherwise, patients of childbearing potential must agree to use 2 effective methods of contraception, where at least 1 form is highly effective, for the entirety of the study and for at least 1 week following the last dose of investigational product.
d. The following contraception methods are considered acceptable (the patient should choose 2, and 1 must be highly effective [defined as less than 1% failure rate per year when used consistently and correctly]):
• Highly effective birth control methods:
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
Progestogen only containing hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
intrauterine device (IUD)/intrauterine hormone releasing system (IUS)
vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate).
• Effective birth control methods:
Male or female condom with spermicide. It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these methods are combined.
Diaphragm with spermicide
Cervical sponge
Cervical cap with spermacide
Note: When local guidelines concerning highly effective or effective methods of birth control differ from the above, the local guidelines must be followed.
Patients of non‒child bearing potential are not required to use birth control and they are defined as:
• women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation who has had either
Cessation of menses for at least 1 year
At least 6 months of spontaneous amenorrhea with follicle stimulating hormone >40 mIU/mL
• Women aged 55 years or older who are not on hormone therapy, and who have had at least 6 months of spontaneous amenorrhea
• Women aged 55 years or older who have a diagnosis of menopause
Informed Consent
[10] Must read and understand the informed consent approved by Eli Lilly and Company (Lilly), or its designee, and the institutional review board (IRB)/ethics review board (ERB) governing the site, and provide written informed consent.
[2] Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
[3] Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 ACR criteria for classification of SLE prior to randomization.
[4] Have 1 or more of the following as assessed by the central lab during screening: a positive antinuclear antibody (ANA; titer ≥1:80), and/or a positive anti dsDNA, and/or a positive anti Smith (anti Sm). Patients with an ANA <1:80 at screening with documentation of a historical ANA ≥1:80 may be eligible, as assessed by the eligibility review committee.
Note: The ANA, anti dsDNA, and anti Smith measurements may be repeated by the central lab once during the screening period, and the value resulting from repeat testing may be accepted for enrollment eligibility if it meets the eligibility criterion.
[5] Have a total SLEDAI 2K score ≥6 during screening, with at least 4 points attributed to clinical items (not including items requiring laboratory value assessment). SLEDAI 2K items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
[6] Have a clinical SLEDAI 2K score ≥4 at Baseline (Visit 2); not including any items requiring laboratory value assessment.
[7] Have at least 1 BILAG A score or 2 BILAG B scores during the screening period. BILAG items requiring laboratory values should be assessed based on the results from the labs drawn during the screening period.
Prior/Concomitant Therapy
[8] Are receiving at least one of the following SoC medications for SLE:
a. A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
b. A single immunosuppressant (such as methotrexate [MTX], azathioprine, mycophenolate, tacrolimus) at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
c. An oral corticosteroid, initiated at least 4 weeks prior to screening (Visit 1), at a stable dose ≤ 40 mg/day prednisone (or equivalent) for at least 2 weeks prior to screening (Visit 1) and through baseline (Visit 2). If the patient is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥ 7.5 mg/day prednisone (or equivalent).
Patient Characteristics
[9] Male or nonpregnant, nonbreastfeeding female patient
a. Patients of child bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same sex relationship without sexual relationships with the opposite sex.
b. Total abstinence is defined as refraining from intercourse during the entirety of the study and for at least 1 week following the last dose of investigational product. Periodic abstinence such as calendar, ovulation, symptothermal, post ovulation methods and withdrawal are not acceptable methods of contraception.
c. Otherwise, patients of childbearing potential must agree to use 2 effective methods of contraception, where at least 1 form is highly effective, for the entirety of the study and for at least 1 week following the last dose of investigational product.
d. The following contraception methods are considered acceptable (the patient should choose 2, and 1 must be highly effective [defined as less than 1% failure rate per year when used consistently and correctly]):
• Highly effective birth control methods:
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
Progestogen only containing hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
intrauterine device (IUD)/intrauterine hormone releasing system (IUS)
vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate).
• Effective birth control methods:
Male or female condom with spermicide. It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these methods are combined.
Diaphragm with spermicide
Cervical sponge
Cervical cap with spermacide
Note: When local guidelines concerning highly effective or effective methods of birth control differ from the above, the local guidelines must be followed.
Patients of non‒child bearing potential are not required to use birth control and they are defined as:
• women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation who has had either
Cessation of menses for at least 1 year
At least 6 months of spontaneous amenorrhea with follicle stimulating hormone >40 mIU/mL
• Women aged 55 years or older who are not on hormone therapy, and who have had at least 6 months of spontaneous amenorrhea
• Women aged 55 years or older who have a diagnosis of menopause
Informed Consent
[10] Must read and understand the informed consent approved by Eli Lilly and Company (Lilly), or its designee, and the institutional review board (IRB)/ethics review board (ERB) governing the site, and provide written informed consent.
Exclusion Criteria
[1] Have severe active lupus nephritis defined clinically and/or by histologic evidence of proliferative glomerulonephritis on renal biopsy (if available) within the 24 weeks prior to screening, or urine protein/creatinine ratio >200 mg/mmol (as an estimate of approximate proteinuria >2 g/day) or eGFR (Modification of Diet in Renal Disease [MDRD]) <40 mL/min/1.73 m2 at screening, or as determined by the eligibility review committee.
Note: The lab measurements related to lupus nephritis may be repeated once by the central lab during the screening period, and the values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
[2] Have active CNS lupus as defined by ACR nomenclature for neuropsychiatric lupus syndromes and as captured by SLEDAI 2K (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and cerebrovascular accident).
[3] Have active fibromyalgia that, in the investigator’s opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study.
[4] Have been treated for or had an active occurrence of a systemic inflammatory condition other than SLE such as, but not limited to, RA, juvenile chronic arthritis, spondyloarthropathy, Crohn’s disease, ulcerative colitis, or psoriatic arthritis within the 12 weeks prior to screening. Patients with secondary Sjögren’s syndrome are not excluded.
[5] Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the patient.
[6] Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study.
[7] Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
[8] Have a history of recurrent (≥ 2) VTE (DVT/PE).
[9] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
[10] Have a history of lymphoproliferative disease; have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE); have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for <5 years prior to randomization.
The following may be exempted:
a. Patients with cervical carcinoma in situ that has been resected with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been completely resected with no evidence of recurrence for at least 3 years may participate in the study.
[11] Have a current or recent (<4 weeks prior to randomization) clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection that in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
Note: For example, a recent viral upper respiratory tract infection or uncomplicated urinary tract infection need not be considered clinically serious.
[12] Have symptomatic herpes simplex at the time of randomization.
[13] Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
[14] Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post herpetic neuralgia).
[15] Have a positive test for hepatitis B virus (HBV) defined as:
a. positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)
Note: Patients who are HBcAb positive and HBV DNA negative may be enrolled in the study but will require additional HBV DNA monitoring during the study.
[16] Have hepatitis C virus (HCV) infection (hepatitis C antibody positive and HCV ribonucleic acid [RNA] positive).
Note: Patients who have documented anti HCV treatment for a past HCV infection AND are HCV RNA negative may be enrolled in the study.
[17] Have evidence of HIV infection and/or positive HIV antibodies.
[18] Have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB.
[19] Have evidence of active TB or latent TB
a. Have evidence of active TB, defined in this study as the following:
• Positive purified protein derivative (PPD) test (≥5 mm induration between approximately 2 and 3 days after application, regardless of vaccination history), medical history, clinical features, and abnormal chest x ray at screening.
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. Patients are excluded from the study if the test is not negative and there is clinical evidence of active TB.
Exception: patients with a history of active TB who have documented evidence of appropriate treatment, have no history of re exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest x ray with no evidence of active TB may be enrolled if other entry criteria met. Such patients would not be required to undergo the protocol specific TB testing for PPD, QuantiFERON® TB Gold test, or T SPOT®.TB test but must have a chest x ray at screening (i.e., a chest x ray performed within the past 6 months will not be accepted).
b. Have evidence of untreated/inadequately or inappropriately treated latent TB, defined in this study as the following:
• Positive PPD test, no clinical features consistent with active TB, and a chest x ray with no evidence of active TB at screening; or
• If the PPD test is positive and the patient has no medical history or chest x ray findings consistent with active TB, the patient may have a QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines). If the test results are not negative, the patient will be considered to have latent TB (for purposes of this study); or
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. If the test results are positive, the patient will be considered to have latent TB. If the test is not negative, the test may be repeated once within approximately 2 weeks of the initial value. If the repeat test results are again not negative, the patient will be considered to have latent TB (for purposes of this study).
Exception: Patients who have evidence of latent TB may be enrolled if he or she completes at least 4 weeks of appropriate treatment prior to randomization and agrees to complete the remainder of treatment while in the trial.
Exception: Patients with a history of latent TB who have documented evidence of appropriate treatment, have no history of re exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest x ray with no evidence of active TB may be enrolled if other entry criteria met. Such patients would not be required to undergo the protocol specific TB testing for PPD, QuantiFERON® TB Gold test, or T SPOT®.TB test but must have a chest x ray at screening (i.e., a chest x ray performed within the past 6 months will not be accepted).
[20] Have received parenteral [i.e., intravenous , intramuscular, intra articular] corticosteroids within 6 weeks of screening (Visit 1), or are expected to require parenteral corticosteroids during the study.
[21] Have received any of the following medications:
a. Biologic treatments for immunologic disease such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, ustekinumab, ixekizumab, secukinumab, or anakinra within 4 weeks of screening.
b. Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti IFN therapy) within 12 weeks of screening.
c. Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg) within 24 weeks of screening.
[22] Have received a JAK inhibitor.
[23] Have been treated with probenecid that cannot be discontinued for the duration of the study.
[24] Have received plasmapheresis within 12 weeks of screening.
[25] Have been exposed to a live vaccine within 12 weeks of randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination).
Note: All patients who have not previously received the herpes zoster vaccine by screening will be encouraged (per local guidelines) to do so prior to randomization; vaccination with live herpes zoster vaccine must occur >4 weeks prior to randomization and start of investigational product. Patients will not be randomized if they were exposed to a live herpes zoster vaccination within 4 weeks of planned randomization. Investigators should review the vaccination status of their patients and follow the local guidelines for vaccination of patients ≥18 years of age with nonlive vaccines intended to prevent infectious disease prior to entering patients into the study.
[26] Are currently enrolled in or have discontinued within 4 weeks of screening from, any other clinical trial involving an investigational product or nonapproved use of a drug or device or any other type of medical research judged not to be scientifically or medically compatible with this study.
[27] Have previously completed or been randomized and withdrawn from this study or any other study investigating baricitinib.
Diagnostics Assessments
[28] Have screening laboratory test values, including thyroid stimulating hormone (TSH), outside the reference range for the population that, in the opinion of the investigator, pose an unacceptable risk for the patient’s participation in the study. Patients who are receiving thyroxine as replacement therapy may participate in the study, provided stable therapy has been administered for ≥12 weeks and TSH is within the laboratory’s reference range. Patients who have TSH marginally outside the laboratory’s normal reference range and are receiving stable thyroxine replacement therapy may participate if the treating physician has documented that the thyroxine replacement therapy is adequate for the patient.
[29] Have any of the following specific abnormalities on screening laboratory tests from the central laboratory:
a. ALT or AST >2 x ULN
b. alkaline phosphatase (ALP) ≥2 x ULN
c. total bilirubin ≥1.5 x ULN
d. hemoglobin <9 g/dL (90.0 g/L)
e. total white blood cell count <2500 cells/µL (<2.50 x 103/µL or <2.50 GI/L)
f. neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) (<1.20 x 103/µL or <1.20 GI/L)
g. lymphopenia (lymphocyte count <500 cells/µL) (<0.50 x 103/µL or <0.50 GI/L)
h. thrombocytopenia (platelets <50,000 cells/µL) (<50 x 103/µL or <50 GI/L)
In the case of any of the aforementioned laboratory abnormalities, the tests may be repeated once by the central laboratory during screening, and values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
Other Exclusions
[30] Are largely or wholly incapacitated permitting little or no self care, such as being bedridden or confined to wheelchair.
[31] In the opinion of the investigator, are at an unacceptable risk for participating in the study.
[32] Have donated more than a single unit of blood within 4 weeks prior to screening or intend to donate blood during the course of the study.
[33] Have a history of intravenous drug abuse, other illicit drug abuse, or chronic alcohol abuse within the 2 years prior to screening or are concurrently using, or expected to use during the study, illicit drugs (including marijuana).
[34] Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures.
[35] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[36] Are Lilly or Incyte employees or their designee.
Note: The lab measurements related to lupus nephritis may be repeated once by the central lab during the screening period, and the values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
[2] Have active CNS lupus as defined by ACR nomenclature for neuropsychiatric lupus syndromes and as captured by SLEDAI 2K (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and cerebrovascular accident).
[3] Have active fibromyalgia that, in the investigator’s opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study.
[4] Have been treated for or had an active occurrence of a systemic inflammatory condition other than SLE such as, but not limited to, RA, juvenile chronic arthritis, spondyloarthropathy, Crohn’s disease, ulcerative colitis, or psoriatic arthritis within the 12 weeks prior to screening. Patients with secondary Sjögren’s syndrome are not excluded.
[5] Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the patient.
[6] Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient’s participation in the study.
[7] Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
[8] Have a history of recurrent (≥ 2) VTE (DVT/PE).
[9] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
[10] Have a history of lymphoproliferative disease; have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE); have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for <5 years prior to randomization.
The following may be exempted:
a. Patients with cervical carcinoma in situ that has been resected with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been completely resected with no evidence of recurrence for at least 3 years may participate in the study.
[11] Have a current or recent (<4 weeks prior to randomization) clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection that in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
Note: For example, a recent viral upper respiratory tract infection or uncomplicated urinary tract infection need not be considered clinically serious.
[12] Have symptomatic herpes simplex at the time of randomization.
[13] Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
[14] Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post herpetic neuralgia).
[15] Have a positive test for hepatitis B virus (HBV) defined as:
a. positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)
Note: Patients who are HBcAb positive and HBV DNA negative may be enrolled in the study but will require additional HBV DNA monitoring during the study.
[16] Have hepatitis C virus (HCV) infection (hepatitis C antibody positive and HCV ribonucleic acid [RNA] positive).
Note: Patients who have documented anti HCV treatment for a past HCV infection AND are HCV RNA negative may be enrolled in the study.
[17] Have evidence of HIV infection and/or positive HIV antibodies.
[18] Have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB.
[19] Have evidence of active TB or latent TB
a. Have evidence of active TB, defined in this study as the following:
• Positive purified protein derivative (PPD) test (≥5 mm induration between approximately 2 and 3 days after application, regardless of vaccination history), medical history, clinical features, and abnormal chest x ray at screening.
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. Patients are excluded from the study if the test is not negative and there is clinical evidence of active TB.
Exception: patients with a history of active TB who have documented evidence of appropriate treatment, have no history of re exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest x ray with no evidence of active TB may be enrolled if other entry criteria met. Such patients would not be required to undergo the protocol specific TB testing for PPD, QuantiFERON® TB Gold test, or T SPOT®.TB test but must have a chest x ray at screening (i.e., a chest x ray performed within the past 6 months will not be accepted).
b. Have evidence of untreated/inadequately or inappropriately treated latent TB, defined in this study as the following:
• Positive PPD test, no clinical features consistent with active TB, and a chest x ray with no evidence of active TB at screening; or
• If the PPD test is positive and the patient has no medical history or chest x ray findings consistent with active TB, the patient may have a QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines). If the test results are not negative, the patient will be considered to have latent TB (for purposes of this study); or
• QuantiFERON® TB Gold test or T SPOT®.TB test (as available and if compliant with local TB guidelines) may be used instead of the PPD test. If the test results are positive, the patient will be considered to have latent TB. If the test is not negative, the test may be repeated once within approximately 2 weeks of the initial value. If the repeat test results are again not negative, the patient will be considered to have latent TB (for purposes of this study).
Exception: Patients who have evidence of latent TB may be enrolled if he or she completes at least 4 weeks of appropriate treatment prior to randomization and agrees to complete the remainder of treatment while in the trial.
Exception: Patients with a history of latent TB who have documented evidence of appropriate treatment, have no history of re exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest x ray with no evidence of active TB may be enrolled if other entry criteria met. Such patients would not be required to undergo the protocol specific TB testing for PPD, QuantiFERON® TB Gold test, or T SPOT®.TB test but must have a chest x ray at screening (i.e., a chest x ray performed within the past 6 months will not be accepted).
[20] Have received parenteral [i.e., intravenous , intramuscular, intra articular] corticosteroids within 6 weeks of screening (Visit 1), or are expected to require parenteral corticosteroids during the study.
[21] Have received any of the following medications:
a. Biologic treatments for immunologic disease such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, ustekinumab, ixekizumab, secukinumab, or anakinra within 4 weeks of screening.
b. Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti IFN therapy) within 12 weeks of screening.
c. Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg) within 24 weeks of screening.
[22] Have received a JAK inhibitor.
[23] Have been treated with probenecid that cannot be discontinued for the duration of the study.
[24] Have received plasmapheresis within 12 weeks of screening.
[25] Have been exposed to a live vaccine within 12 weeks of randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination).
Note: All patients who have not previously received the herpes zoster vaccine by screening will be encouraged (per local guidelines) to do so prior to randomization; vaccination with live herpes zoster vaccine must occur >4 weeks prior to randomization and start of investigational product. Patients will not be randomized if they were exposed to a live herpes zoster vaccination within 4 weeks of planned randomization. Investigators should review the vaccination status of their patients and follow the local guidelines for vaccination of patients ≥18 years of age with nonlive vaccines intended to prevent infectious disease prior to entering patients into the study.
[26] Are currently enrolled in or have discontinued within 4 weeks of screening from, any other clinical trial involving an investigational product or nonapproved use of a drug or device or any other type of medical research judged not to be scientifically or medically compatible with this study.
[27] Have previously completed or been randomized and withdrawn from this study or any other study investigating baricitinib.
Diagnostics Assessments
[28] Have screening laboratory test values, including thyroid stimulating hormone (TSH), outside the reference range for the population that, in the opinion of the investigator, pose an unacceptable risk for the patient’s participation in the study. Patients who are receiving thyroxine as replacement therapy may participate in the study, provided stable therapy has been administered for ≥12 weeks and TSH is within the laboratory’s reference range. Patients who have TSH marginally outside the laboratory’s normal reference range and are receiving stable thyroxine replacement therapy may participate if the treating physician has documented that the thyroxine replacement therapy is adequate for the patient.
[29] Have any of the following specific abnormalities on screening laboratory tests from the central laboratory:
a. ALT or AST >2 x ULN
b. alkaline phosphatase (ALP) ≥2 x ULN
c. total bilirubin ≥1.5 x ULN
d. hemoglobin <9 g/dL (90.0 g/L)
e. total white blood cell count <2500 cells/µL (<2.50 x 103/µL or <2.50 GI/L)
f. neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) (<1.20 x 103/µL or <1.20 GI/L)
g. lymphopenia (lymphocyte count <500 cells/µL) (<0.50 x 103/µL or <0.50 GI/L)
h. thrombocytopenia (platelets <50,000 cells/µL) (<50 x 103/µL or <50 GI/L)
In the case of any of the aforementioned laboratory abnormalities, the tests may be repeated once by the central laboratory during screening, and values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
Other Exclusions
[30] Are largely or wholly incapacitated permitting little or no self care, such as being bedridden or confined to wheelchair.
[31] In the opinion of the investigator, are at an unacceptable risk for participating in the study.
[32] Have donated more than a single unit of blood within 4 weeks prior to screening or intend to donate blood during the course of the study.
[33] Have a history of intravenous drug abuse, other illicit drug abuse, or chronic alcohol abuse within the 2 years prior to screening or are concurrently using, or expected to use during the study, illicit drugs (including marijuana).
[34] Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures.
[35] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[36] Are Lilly or Incyte employees or their designee.
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
participants
