Clinical Trials List
Protocol NumberB7931028
NCT Number(ClinicalTrials.gov Identfier)NCT03845517
Completed
2019-10-31 - 2023-10-05
Phase II
Recruiting8
A PHASE 2B, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-06700841 IN PARTICIPANTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
-
Sponsor
Pfizer
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Po-Hao Huang 風濕免疫科
- Chen Der-Yuan 風濕免疫科
- 黃建中 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- HSIN-HUA CHEN 無
- 譚國棟 無
- 謝佳偉 無
- 林靖才 無
- 陳彥如 無
- WEN-NAN HUANG 無
- Yi-Ming Chen 無
- 曾智偉 無
- 謝祖怡 無
- 洪維廷 無
- 吳沂達 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳彥輔 無
- TianMing Zhan 無
- Shue-Fen Lo 無
- Ping-Han Tsai 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 呂明錡 無
- 童建學 無
- CHENG-HAN WU 無
- 黃光永 無
- 許寶寶 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- SONG-CHOU HSIEH 風濕免疫科
- 呂政勳 風濕免疫科
- 郭佑民 風濕免疫科
- CHENG-HAN WU 風濕免疫科
- CHIEH-YU SHEN 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Systemic Lupus Erythematosus（SLE)
Objectives
Assessment of PF-06700841 in participants with moderate to severe active, generalized Systemic Lupus Erythematosus (SLE) that have inadequate response to standard of care.
Test Drug
PF-06700841
Active Ingredient
PF-06700841
Dosage Form
tablets
tablets
tablets
Dosage
25
5
5
Endpoints
Primary Outcome Measures :
Proportion of participants achieving the Systemic Lupus Erythematosus Responder Index (SRI) change of 4 (SRI-4) at Week 52. [ Time Frame: Week 52 ]
Proportion of participants achieving the Systemic Lupus Erythematosus Responder Index (SRI) change of 4 (SRI-4) at Week 52. [ Time Frame: Week 52 ]
Inclution Criteria
1. Male or female participantsbetween the ages of 18 (or the minimum country-specific age of consent if >18) and 75years, inclusive, at the time of signing the informed consent document (ICD).
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other studyprocedures.
3. Have a clinical diagnosis of SLE according to the 1997update on the 1982 revised American College of Rheumatology (ACR) Criteria for the Classification of SLE see Appendix 8 OR meetat least 4 of the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria see Appendix 9, including at least 1 clinical criterion and 1 immunologic criterion, at least 6 months prior to dosing of study agent.
4. Have serologically positive SLE at the screening visit based on 1 of the following test results from the central laboratory during the screening period:
ANA titer >=1:80, or
Positive anti-dsDNA.
Note: The ANA and/oranti double stranded DNA(anti-dsDNA) measurement may be repeated once at the central laboratory within approximately 2 weeks of the initial value, andthe value resulting from repeat testing may be accepted for enrollment eligibility if it meets the eligibility criterion.
5. All participants must be currently receiving a stable dose of/or have documented failed therapy with one of the following: methotrexate (MTX), azathioprine (AZA), mycophenolate/mycophenolic acid (MMF), anti-malarials (hydroxychloroquine or chloroquine) or corticosteroids (if monotherapy, greater than or equal to 7.5 mg per day)
Note:Stable dose is defined as no new therapy or change in standard-of-care therapies as above within 12 weeks of Day 1. See Appendix 13for allowable stable doses. Documented failure must be outlined in the participants medical notes or similar source document.
6. Have active disease defined as:
SLEDAI-2K score of >=6 points at screening, and “Clinical” SLEDAI-2K score of 4 points at both screening and randomization
AND
BILAG Level A disease in >=1 organ system (except renal or central nervous system [CNS]) or BILAG B disease in >=2 organ systems if no levelA disease is presentat screening. In addition, 1A and/or 2B BILAG need to be the same clinical disease manifestation(s) at baseline(see Appendix 12) .
7. Participants weighing greater than 35 kg and less than 130 kg .
8. Capable of giving signed informed consent as described inAppendix 1, which includes compliance with the requirements and restrictionslisted in the ICD and in this protocol.
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other studyprocedures.
3. Have a clinical diagnosis of SLE according to the 1997update on the 1982 revised American College of Rheumatology (ACR) Criteria for the Classification of SLE see Appendix 8 OR meetat least 4 of the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria see Appendix 9, including at least 1 clinical criterion and 1 immunologic criterion, at least 6 months prior to dosing of study agent.
4. Have serologically positive SLE at the screening visit based on 1 of the following test results from the central laboratory during the screening period:
ANA titer >=1:80, or
Positive anti-dsDNA.
Note: The ANA and/oranti double stranded DNA(anti-dsDNA) measurement may be repeated once at the central laboratory within approximately 2 weeks of the initial value, andthe value resulting from repeat testing may be accepted for enrollment eligibility if it meets the eligibility criterion.
5. All participants must be currently receiving a stable dose of/or have documented failed therapy with one of the following: methotrexate (MTX), azathioprine (AZA), mycophenolate/mycophenolic acid (MMF), anti-malarials (hydroxychloroquine or chloroquine) or corticosteroids (if monotherapy, greater than or equal to 7.5 mg per day)
Note:Stable dose is defined as no new therapy or change in standard-of-care therapies as above within 12 weeks of Day 1. See Appendix 13for allowable stable doses. Documented failure must be outlined in the participants medical notes or similar source document.
6. Have active disease defined as:
SLEDAI-2K score of >=6 points at screening, and “Clinical” SLEDAI-2K score of 4 points at both screening and randomization
AND
BILAG Level A disease in >=1 organ system (except renal or central nervous system [CNS]) or BILAG B disease in >=2 organ systems if no levelA disease is presentat screening. In addition, 1A and/or 2B BILAG need to be the same clinical disease manifestation(s) at baseline(see Appendix 12) .
7. Participants weighing greater than 35 kg and less than 130 kg .
8. Capable of giving signed informed consent as described inAppendix 1, which includes compliance with the requirements and restrictionslisted in the ICD and in this protocol.
Exclusion Criteria
1. Have active renal lupus as defined by the following: spot urine protein/creatinine ratio >3.0 mg/g (proteinuria >3.0 g/24 hours may also be used if available) or have BILAG A renal disease, or have required hemodialysis or active urinarysediment with red blood cell cast(s), or histological evidence (if available) of diffuse proliferative glomerulonephritis within the 12 weeks prior to screening.
2. Have severe active central nervous system (CNS) lupus (eg, BILAG A neurological disease and/or active, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia or dementia related to SLE, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60days of Day1. Patients with BILAG Blevel neurologic disease are not excluded as long as they meet all other qualifying criteria for the study.
3. Have cancer or a history of cancer within 5years of screening (other than adequately resected cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence within the previous 3 years).
4. Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplantor total lymphoid irradiation.
5. Have a history of thrombosis (venous or arterial) or other vascular complications within the last 6months, or any history of either recurrent thrombosis or a pulmonary embolus.
6. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) or any history of significant cerebrovascular disease within 24weeks of screening.
7. Have pre-existing demyelinating disorder such as multiple sclerosis, or other severe neurological deficitsor any other autoimmune disorder that would interfere with interpretation of efficacy and safety data.
8. A history of additional risk factors for torsade de pointes (TdP) (eg, heart failure [New York Heart Association status of class III or IV], hypokalemia, familyhistory of Long QT Syndrome).
9. A participantwith any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary
10. Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE);
11. Have active fibromyalgia/myofascial/chronic pain that, in the investigator’s opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study.
12. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation(defined in Section 8.2.10) or behavior or laboratory abnormality that may increase the risk associated with studyparticipation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participantinappropriate for entry into this study
13. Participation in other interventional studies within 4 weeks or 5half-lives, if known, whichever is longer, prior to study entry and/or during study participation. Participation in any observational studies during study participation.
14. The following use of corticosteroids is exclusionary;
Receiving >=20 mg/ day of prednisone or equivalent (see Appendix 14) or have adjusted the dose of corticosteroids within 2 weeks of Day 1.
Have received oral or parenteral [intravenous (IV) or intramuscular (IM)] corticosteroids at doses >40-mg per day of prednisone (or equivalentseeAppendix 14) within within 8 weeks of Day 1, or are anticipated to require parenteral injection of corticosteroids during the study.
Have had a joint injected with intra-articular corticosteroids or hyaluronic acid within within 4 weeks of Day 1.
Have received topical corticosteroids, other than stable doses of class 6 (mild, such as desonide) or class 7 (least potent, such as hydrocortisone), within 4 weeks of Day 1.
15. Have started or stopped treatment or adjusted the dose of antimalarials within 12 weeks of Day 1.
16. Have started or stopped treatment with an accepted standard of care immunosuppressant (azathioprine, methotrexate or mycophenolate) within 12 weeks of Day 1. The dose of immunosuppressants should be as stable as possible within 12 weeks of Day 1 and shouldonly be changed for toxicity documented in the source document. No changes in the dose of immunosuppressants are acceptable within 2 weeks of Day 1. Please see Appendix 13for acceptable doses.
17. Additional immunomodulatory drug considerationssee Appendix 13:
No systemic calcineurin inhibitors within 12 weeks of Day 1 except for optic topical preparations (eye drops)
No cyclophosphamide or chlorambucil use within 24 weeksof Day 1
No anti tumor necrosis factor (anti-TNF) inhibitors (adlimumab, etanercept, infliximab, certolizumab, golimumab), anakinraor belimumab within 12 weeks of Day 1
No tocilizumab, ustekinumab, or abatacept within 24 weeks of Day 1
No rituximab, or investigational B cell targeted therapies within 24weeks of Day 1
No investigational biologic therapies within 12 weeks of Day 1
No history of hydroxyurea treatment.
No history of prior treatment with any lymphoid depleting therapy ( Campath, anti-CD3, Lemtrada, alemtuzumab, total lymphoid irradiation)
18. Have received plasmapheresis within 12 weeks of screening or intravenous immunoglobulin (IVIg) within 24 weeks of screening.
19. Treatment with an approved or investigational JAK inhibitor (ie, tofacitinib, baricitinib, filgotinib, upadacitinib)
20. Participationin any studies with kinase inhibitors within 12 weeks of Day 1.
21. Treatment with any non biologic investigational drug(s) within 4weeks of Day 1 or within 5 half-lives, if known, whichever is longer, and/or during studyparticipation.
22. Has been exposed to a live vaccine within 6 weeks of Day1 or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination- refer to EC #33 below). Participants should not have received a Bacillus Calmette-Guérin (BCG) vaccination within 52 weeks of randomization.
23. Use of concomitant medications known toprolong the QT interval.
24. Require concomitant treatment with prohibited concomitant medications (seeAppendix
25. Active bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, allergic aspergillosis or cavitary lung lesions or granulomatous disease on chest x-ray). History of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to TB and atypical mycobacterial disease, granulomatous disease on chest x-ray) that would substantially increase the risk to the participantif he or she participates in the study.
26. Have a history of any lymphoproliferative disorder such as Epstein-Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE);
27. Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or recurrent (more than 1 episode within last 5 years) localized, dermatomal herpes zoster.Note: All participants who have not received the herpes zoster vaccine at screening will be encouraged (per local guidelines) to do so prior to randomization; vaccination must occur >4 weeks prior to randomization and start of investigational product. Patients will be excluded if they were exposed to live herpes zoster vaccination within 4 weeks of planned randomization
28. Known history of human immunodeficiencyvirus(HIV) based on documented history with positive serological test, or positive HIV serological test atscreening.
Note: a documented negative HIV test within 12 weeks of screening is acceptable and does not need to be repeated.
29. Have evidence of clinically significant active or latent infection of hepatitis B or hepatitis C based on screening tests (see Section 8.2.5).
30. Have clinically relevantfinding on a chest radiograph (or other appropriate diagnostic imaging study such as computed tomography [CT] or magnetic resonance imaging [MRI]) such as the presence of TB, general infection, heart failure or malignancy. Findings due to SLE activity do not require the participantto be excluded.
31. Have required management of acute or chronic infections as follows:13).
Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus [CMV], and atypical mycobacteria) that, inthe opinion of the investigator and sponsor, would place the participantat risk for reactivation. Participantsreceiving prophylactic therapy for prior outbreaks of herpes simplex virus may be enrolled with the expectation that this treatment will continue for the duration of the study.
Hospitalization for treatment of serious infections within 60days of Day1.
Use of IV or IM antibacterials, antivirals, antifungals, or anti-parasitic agents within 60days of Day1. Substitution of IM agents for oral agents because of gastrointestinal (GI) intolerance may be acceptable, as long as it does not otherwise meet the criteria for a serious infection (requires hospitalization or use of other IV antibiotics).
Use of oral antibiotics to treat an active infection within 14days of Day1.
32. Infected with Mycobacterium tuberculosis(TB) as defined by anyof the following:
A positive interferon gamma release assay (IGRA) test performed at or within the 12weeks prior to Day1 is exclusionary; a negative test is required for eligibility. The following are acceptable IGRA assays: T-SPOT
TB test (preferable, where available), QuantiFERON
- TB Gold In-Tube test (QFT-GIT), QuantiFERON
- TB Gold test (QFT-G) or QuantiFERON
-TB Gold Plus test (QFT-G Plus). In participantswith a history of Bacillus Calmette-Guérin (BCG) vaccination, the IGRA test is strongly recommended since the Mantoux test (tuberculin, purified protein derivative [PPD] skin test) may be positive due to vaccination.
If the results of the IGRA are indeterminate, the test may be repeated, and if a negative resultis obtained, enrollment may proceed. A positive test on repeat is exclusionary.
Participantswith repeat indeterminate IGRA results may be enrolled after consultation with an infectious disease and/or pulmonary specialist and Sponsor is in agreement.
Note: Participantswith a history of active or latent TB are excluded.
Chest radiograph taken at screening with changes suggestive of active TB infection, unless previously performed and documented within 12weeks prior to Day1.
33. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or brady-arrhythmias) or that are indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson-White syndrome) and other clinically relevant abnormalities which may affect participantsafety or interpretation of study results. Specifically, participantwith screening Fredericia corrected QT interval (QTcF) >450milliseconds (msec) should be excluded. If QTcF exceeds 450msec, the ECG should be repeated two more times and the average of the three QTcF should be used to determine the participanteligibility.
34. Participantswith ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
Total immunoglobulin levels below lower limits of normal
Hemoglobin <9 g/dL (<90 g/L);
Absolute neutrophil count(ANC)<1.2 x 109/L (<1200 mm3);
Absolute lymphocyte count (ALC) of <0.75 x 109/L (<750/mm3); Note: Patients may be enrolled with a ALC <0.75 x 109/L but ≥0.5 x 109/L if the ALC is considered by the investigator to be a result of the underlying SLE disease or concomitant medications.
Platelet count <75 x 109/L (<75,000/mm3);
Serum cystatinC-based estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2based on the age appropriate calculation;
Urine protein to urine creatinine (UPr:UCr) ratio >3.0 mg/mg.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values
2 times the ULN;
Total bilirubin
1.5 times the ULN; participantswith a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is
35. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
36. Have a history of severe allergic or anaphylactoid reaction to kinase inhibitors.
37. Have had significant trauma ormajor surgeryor blood transfusionwithin 4weeks of screening, or scheduled to occur during the study, excluding diagnostic surgery.
38. History of alcohol or drug abuse in investigator’s opinion unless in full remission for greater than 12months prior to first dose of study medication.
2. Have severe active central nervous system (CNS) lupus (eg, BILAG A neurological disease and/or active, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia or dementia related to SLE, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60days of Day1. Patients with BILAG Blevel neurologic disease are not excluded as long as they meet all other qualifying criteria for the study.
3. Have cancer or a history of cancer within 5years of screening (other than adequately resected cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence within the previous 3 years).
4. Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplantor total lymphoid irradiation.
5. Have a history of thrombosis (venous or arterial) or other vascular complications within the last 6months, or any history of either recurrent thrombosis or a pulmonary embolus.
6. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) or any history of significant cerebrovascular disease within 24weeks of screening.
7. Have pre-existing demyelinating disorder such as multiple sclerosis, or other severe neurological deficitsor any other autoimmune disorder that would interfere with interpretation of efficacy and safety data.
8. A history of additional risk factors for torsade de pointes (TdP) (eg, heart failure [New York Heart Association status of class III or IV], hypokalemia, familyhistory of Long QT Syndrome).
9. A participantwith any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary
10. Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE);
11. Have active fibromyalgia/myofascial/chronic pain that, in the investigator’s opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study.
12. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation(defined in Section 8.2.10) or behavior or laboratory abnormality that may increase the risk associated with studyparticipation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participantinappropriate for entry into this study
13. Participation in other interventional studies within 4 weeks or 5half-lives, if known, whichever is longer, prior to study entry and/or during study participation. Participation in any observational studies during study participation.
14. The following use of corticosteroids is exclusionary;
Receiving >=20 mg/ day of prednisone or equivalent (see Appendix 14) or have adjusted the dose of corticosteroids within 2 weeks of Day 1.
Have received oral or parenteral [intravenous (IV) or intramuscular (IM)] corticosteroids at doses >40-mg per day of prednisone (or equivalentseeAppendix 14) within within 8 weeks of Day 1, or are anticipated to require parenteral injection of corticosteroids during the study.
Have had a joint injected with intra-articular corticosteroids or hyaluronic acid within within 4 weeks of Day 1.
Have received topical corticosteroids, other than stable doses of class 6 (mild, such as desonide) or class 7 (least potent, such as hydrocortisone), within 4 weeks of Day 1.
15. Have started or stopped treatment or adjusted the dose of antimalarials within 12 weeks of Day 1.
16. Have started or stopped treatment with an accepted standard of care immunosuppressant (azathioprine, methotrexate or mycophenolate) within 12 weeks of Day 1. The dose of immunosuppressants should be as stable as possible within 12 weeks of Day 1 and shouldonly be changed for toxicity documented in the source document. No changes in the dose of immunosuppressants are acceptable within 2 weeks of Day 1. Please see Appendix 13for acceptable doses.
17. Additional immunomodulatory drug considerationssee Appendix 13:
No systemic calcineurin inhibitors within 12 weeks of Day 1 except for optic topical preparations (eye drops)
No cyclophosphamide or chlorambucil use within 24 weeksof Day 1
No anti tumor necrosis factor (anti-TNF) inhibitors (adlimumab, etanercept, infliximab, certolizumab, golimumab), anakinraor belimumab within 12 weeks of Day 1
No tocilizumab, ustekinumab, or abatacept within 24 weeks of Day 1
No rituximab, or investigational B cell targeted therapies within 24weeks of Day 1
No investigational biologic therapies within 12 weeks of Day 1
No history of hydroxyurea treatment.
No history of prior treatment with any lymphoid depleting therapy ( Campath, anti-CD3, Lemtrada, alemtuzumab, total lymphoid irradiation)
18. Have received plasmapheresis within 12 weeks of screening or intravenous immunoglobulin (IVIg) within 24 weeks of screening.
19. Treatment with an approved or investigational JAK inhibitor (ie, tofacitinib, baricitinib, filgotinib, upadacitinib)
20. Participationin any studies with kinase inhibitors within 12 weeks of Day 1.
21. Treatment with any non biologic investigational drug(s) within 4weeks of Day 1 or within 5 half-lives, if known, whichever is longer, and/or during studyparticipation.
22. Has been exposed to a live vaccine within 6 weeks of Day1 or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination- refer to EC #33 below). Participants should not have received a Bacillus Calmette-Guérin (BCG) vaccination within 52 weeks of randomization.
23. Use of concomitant medications known toprolong the QT interval.
24. Require concomitant treatment with prohibited concomitant medications (seeAppendix
25. Active bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, allergic aspergillosis or cavitary lung lesions or granulomatous disease on chest x-ray). History of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to TB and atypical mycobacterial disease, granulomatous disease on chest x-ray) that would substantially increase the risk to the participantif he or she participates in the study.
26. Have a history of any lymphoproliferative disorder such as Epstein-Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of lymphoproliferative disease, including lymphadenopathy or splenomegaly (other than primarily due to SLE);
27. Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or recurrent (more than 1 episode within last 5 years) localized, dermatomal herpes zoster.Note: All participants who have not received the herpes zoster vaccine at screening will be encouraged (per local guidelines) to do so prior to randomization; vaccination must occur >4 weeks prior to randomization and start of investigational product. Patients will be excluded if they were exposed to live herpes zoster vaccination within 4 weeks of planned randomization
28. Known history of human immunodeficiencyvirus(HIV) based on documented history with positive serological test, or positive HIV serological test atscreening.
Note: a documented negative HIV test within 12 weeks of screening is acceptable and does not need to be repeated.
29. Have evidence of clinically significant active or latent infection of hepatitis B or hepatitis C based on screening tests (see Section 8.2.5).
30. Have clinically relevantfinding on a chest radiograph (or other appropriate diagnostic imaging study such as computed tomography [CT] or magnetic resonance imaging [MRI]) such as the presence of TB, general infection, heart failure or malignancy. Findings due to SLE activity do not require the participantto be excluded.
31. Have required management of acute or chronic infections as follows:13).
Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus [CMV], and atypical mycobacteria) that, inthe opinion of the investigator and sponsor, would place the participantat risk for reactivation. Participantsreceiving prophylactic therapy for prior outbreaks of herpes simplex virus may be enrolled with the expectation that this treatment will continue for the duration of the study.
Hospitalization for treatment of serious infections within 60days of Day1.
Use of IV or IM antibacterials, antivirals, antifungals, or anti-parasitic agents within 60days of Day1. Substitution of IM agents for oral agents because of gastrointestinal (GI) intolerance may be acceptable, as long as it does not otherwise meet the criteria for a serious infection (requires hospitalization or use of other IV antibiotics).
Use of oral antibiotics to treat an active infection within 14days of Day1.
32. Infected with Mycobacterium tuberculosis(TB) as defined by anyof the following:
A positive interferon gamma release assay (IGRA) test performed at or within the 12weeks prior to Day1 is exclusionary; a negative test is required for eligibility. The following are acceptable IGRA assays: T-SPOT
TB test (preferable, where available), QuantiFERON
- TB Gold In-Tube test (QFT-GIT), QuantiFERON
- TB Gold test (QFT-G) or QuantiFERON
-TB Gold Plus test (QFT-G Plus). In participantswith a history of Bacillus Calmette-Guérin (BCG) vaccination, the IGRA test is strongly recommended since the Mantoux test (tuberculin, purified protein derivative [PPD] skin test) may be positive due to vaccination.
If the results of the IGRA are indeterminate, the test may be repeated, and if a negative resultis obtained, enrollment may proceed. A positive test on repeat is exclusionary.
Participantswith repeat indeterminate IGRA results may be enrolled after consultation with an infectious disease and/or pulmonary specialist and Sponsor is in agreement.
Note: Participantswith a history of active or latent TB are excluded.
Chest radiograph taken at screening with changes suggestive of active TB infection, unless previously performed and documented within 12weeks prior to Day1.
33. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or brady-arrhythmias) or that are indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson-White syndrome) and other clinically relevant abnormalities which may affect participantsafety or interpretation of study results. Specifically, participantwith screening Fredericia corrected QT interval (QTcF) >450milliseconds (msec) should be excluded. If QTcF exceeds 450msec, the ECG should be repeated two more times and the average of the three QTcF should be used to determine the participanteligibility.
34. Participantswith ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
Total immunoglobulin levels below lower limits of normal
Hemoglobin <9 g/dL (<90 g/L);
Absolute neutrophil count(ANC)<1.2 x 109/L (<1200 mm3);
Absolute lymphocyte count (ALC) of <0.75 x 109/L (<750/mm3); Note: Patients may be enrolled with a ALC <0.75 x 109/L but ≥0.5 x 109/L if the ALC is considered by the investigator to be a result of the underlying SLE disease or concomitant medications.
Platelet count <75 x 109/L (<75,000/mm3);
Serum cystatinC-based estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2based on the age appropriate calculation;
Urine protein to urine creatinine (UPr:UCr) ratio >3.0 mg/mg.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values
2 times the ULN;
Total bilirubin
1.5 times the ULN; participantswith a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is
35. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
36. Have a history of severe allergic or anaphylactoid reaction to kinase inhibitors.
37. Have had significant trauma ormajor surgeryor blood transfusionwithin 4weeks of screening, or scheduled to occur during the study, excluding diagnostic surgery.
38. History of alcohol or drug abuse in investigator’s opinion unless in full remission for greater than 12months prior to first dose of study medication.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
448 participants
