Clinical Trials List
Protocol Number015K-CL-CNA3
NCT Number(ClinicalTrials.gov Identfier)無NCT03660059
2018-11-01 - 2022-06-21
Phase III
Terminated5
ICD-10M06.9
Rheumatoid arthritis, unspecified
ICD-10M06
Other rheumatoid arthritis
A Randomized, Double-Blind, Placebo-Controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients with Rheumatoid Arthritis (RA) who Had an Inadequate Response or Intolerance to MTX
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
Astellas Pharma
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Po-Hao Huang 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- WEN-NAN HUANG Division of Rheumatology
- Yi-Ming Chen Division of Rheumatology
- 曾智偉 Division of Rheumatology
- 洪維廷 Division of Rheumatology
- 賴國隆 Division of Rheumatology
- 謝祖怡 Division of Rheumatology
- HSIN-HUA CHEN Division of Rheumatology
- 周吟怡 Division of Rheumatology
- 謝佳偉 Division of Rheumatology
- 林靖才 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Hui-Ching Hsu Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Tzn-Min Lin 風濕免疫科
The Actual Total Number of Participants Enrolled
5 Completed
Audit
None
Condition/Disease
Rheumatoid Arthritis (RA)
Objectives
The objectives of the study are as follows:
To verify the superiority of ASP015K in combination with methotrexate (MTX) or with other diseasemodifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy, at doses of 100 mg/day
and 150 mg/day, in patients with rheumatoid arthritis (RA) who had an inadequate response or
intolerance to MTX , as measured by the ACR20 response rate at Week 24, which is the primary
variable; To evaluate the pharmacokinetics and safety of ASP015K; To evaluate the efficacy and safety
of long-term treatment with ASP015K (52 weeks).
Test Drug
ASP015K
Active Ingredient
ASP015K (Peficitinib hydrobromide)
Dosage Form
tablet
Dosage
50 mg
Endpoints
Endpoints for Evaluation:
Efficacy:
1) Primary Variables
• ACR20 response rate at Week 24
2) Secondary Variables
• ACR20 response rate
• ACR50 response rate
• ACR70 response rate
• Change from baseline in DAS28-CRP and DAS28-ESR scores
• Change from baseline in Tender Joint Count (TJC) (68 joints)
• Change from baseline in Swollen Joint Count (SJC) (66 joints)
• Percentage of subjects achieving DAS28-CRP and DAS28-ESR scores for remission
• Percentage of subjects achieving low disease activity by DAS28-CRP and DAS28-ESR
• Change from baseline in CRP and ESR
• Percentage of subjects with good EULAR response
• Percentage of subjects with good or moderate EULAR response
• Percentage of subjects achieving ACR/EULAR remission. If all of the following 4 parameters
are fulfilled, it is defined as remission:
➢ TJC ≤ 1
➢ SJC ≤ 1
➢ CRP ≤ 1 mg/dL
➢ Subject’s Global Assessment of Arthritis (SGA) ≤ 1 cm (on a VAS of 0–100 mm)
• Percentage of subjects achieving SDAI remission (SDAI score ≤ 3.3)
• Change from baseline in SDAI score
• Change from baseline in Physician’s Global Assessment of Arthritis (PGA) (VAS)
• Change from baseline in SGA (VAS)
• Change from baseline in subject’s assessment of pain (VAS)
• Incidence of subject withdrawal due to the lack of efficacy
• Change from baseline in HAQ-DI score
• Change from baseline in SF-36v2® score
• Change from baseline in WPAI score
Safety:
• AEs
• Vital signs (body temperature, pulse rate, and blood pressure in a sitting position)
• Body weight
• 12-lead electrocardiogram (ECG)
• Central electrocardiogram
• Chest radiography
• Laboratory assessments
Efficacy:
1) Primary Variables
• ACR20 response rate at Week 24
2) Secondary Variables
• ACR20 response rate
• ACR50 response rate
• ACR70 response rate
• Change from baseline in DAS28-CRP and DAS28-ESR scores
• Change from baseline in Tender Joint Count (TJC) (68 joints)
• Change from baseline in Swollen Joint Count (SJC) (66 joints)
• Percentage of subjects achieving DAS28-CRP and DAS28-ESR scores for remission
• Percentage of subjects achieving low disease activity by DAS28-CRP and DAS28-ESR
• Change from baseline in CRP and ESR
• Percentage of subjects with good EULAR response
• Percentage of subjects with good or moderate EULAR response
• Percentage of subjects achieving ACR/EULAR remission. If all of the following 4 parameters
are fulfilled, it is defined as remission:
➢ TJC ≤ 1
➢ SJC ≤ 1
➢ CRP ≤ 1 mg/dL
➢ Subject’s Global Assessment of Arthritis (SGA) ≤ 1 cm (on a VAS of 0–100 mm)
• Percentage of subjects achieving SDAI remission (SDAI score ≤ 3.3)
• Change from baseline in SDAI score
• Change from baseline in Physician’s Global Assessment of Arthritis (PGA) (VAS)
• Change from baseline in SGA (VAS)
• Change from baseline in subject’s assessment of pain (VAS)
• Incidence of subject withdrawal due to the lack of efficacy
• Change from baseline in HAQ-DI score
• Change from baseline in SF-36v2® score
• Change from baseline in WPAI score
Safety:
• AEs
• Vital signs (body temperature, pulse rate, and blood pressure in a sitting position)
• Body weight
• 12-lead electrocardiogram (ECG)
• Central electrocardiogram
• Chest radiography
• Laboratory assessments
Inclution Criteria
1. Subject has received a full explanation of the study drug and this study in advance, and written informed consent to participate in the
study has been obtained from the subject himself/herself.
2. Subject is a man or woman and considered to be an adult, according to the local legal definition, at the time of informed consent.
3. Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of
Rheumatology/European League against Rheumatism (ACR/EULAR) criteria.
4. Subject who did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline
(start of treatment) for RA treatment: Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or
equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent).
5. At screening subject has active RA as evidenced by both of the following:
≥ 6 tender/painful joints (using 68-joint assessment)
≥ 6 swollen joints (using 66-joint assessment)
6. CRP (latex agglutination test) > 0.50 mg/dL at screening
7. Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III at screening.
8. Subjects who are judged to be inadequate responder or intolerant for MTX at the time of screening with well documented relative medical
history and diagnosis rationale by the screening.
9. For inadequate responders to MTX, they have had regular use of MTX for at least 90 days prior to screening at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable,
unchanging oral dose of 7.5 to 20 mg/week (or the equivalent injectable dose) for at least the 28days prior to screening. Subject is able to continue stable dose of MTX from at least 28 days prior to screening until the end of the administration period of study drug.
10. For subjects who are intolerant of MTX, they have had regular use of the following DMARDs, and when the following DMARDs are
concomitantly administered to subject, the drugs must be administered for at least 90 days prior to screening, and must be stable from at
least 28 days prior to screening until the end of the administration period of study drug.
Hydroxychloroquine
Salazosulfapyridine
Gold
D-penicillamine
Lobenzarit
Actarit
Bucillamine
Iguratimod
11. Subject must be willing and able to comply with the study requirements.
[Rationale for Inclusion Criteria]
1: Established with consideration for ethics of conducting the study.
2: Established to ensure ethical and safe conduct of the study.
3: Established to select RA patients relevant for this study. Taking note of the recent changes in RA diagnostic criteria and current
practices in clinical settings, patients conforming to either the 1987 ACR or the 2010 ACR/EULAR criteria have been defined eligible for
inclusion.
4: Established because these drugs are used to improve QOL of RA patients and may possibly impact the efficacy evaluation of ASP015K.
5 and 6: Established to define the range of RA disease activity pertinent to this study.
7: Established to identify patients appropriate for evaluation using the classification criteria for functional status.
8: Established to select patients who had an inadequate response or intolerance to MTX.
9, 10: Established to choose patients who can maintain the same dosage and administration schedule for concomitant MTX or other DMARDs from before baseline and throughout the treatment period.
11: Established to ensure the integrity of the study evaluation.
study has been obtained from the subject himself/herself.
2. Subject is a man or woman and considered to be an adult, according to the local legal definition, at the time of informed consent.
3. Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of
Rheumatology/European League against Rheumatism (ACR/EULAR) criteria.
4. Subject who did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline
(start of treatment) for RA treatment: Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or
equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent).
5. At screening subject has active RA as evidenced by both of the following:
≥ 6 tender/painful joints (using 68-joint assessment)
≥ 6 swollen joints (using 66-joint assessment)
6. CRP (latex agglutination test) > 0.50 mg/dL at screening
7. Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III at screening.
8. Subjects who are judged to be inadequate responder or intolerant for MTX at the time of screening with well documented relative medical
history and diagnosis rationale by the screening.
9. For inadequate responders to MTX, they have had regular use of MTX for at least 90 days prior to screening at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable,
unchanging oral dose of 7.5 to 20 mg/week (or the equivalent injectable dose) for at least the 28days prior to screening. Subject is able to continue stable dose of MTX from at least 28 days prior to screening until the end of the administration period of study drug.
10. For subjects who are intolerant of MTX, they have had regular use of the following DMARDs, and when the following DMARDs are
concomitantly administered to subject, the drugs must be administered for at least 90 days prior to screening, and must be stable from at
least 28 days prior to screening until the end of the administration period of study drug.
Hydroxychloroquine
Salazosulfapyridine
Gold
D-penicillamine
Lobenzarit
Actarit
Bucillamine
Iguratimod
11. Subject must be willing and able to comply with the study requirements.
[Rationale for Inclusion Criteria]
1: Established with consideration for ethics of conducting the study.
2: Established to ensure ethical and safe conduct of the study.
3: Established to select RA patients relevant for this study. Taking note of the recent changes in RA diagnostic criteria and current
practices in clinical settings, patients conforming to either the 1987 ACR or the 2010 ACR/EULAR criteria have been defined eligible for
inclusion.
4: Established because these drugs are used to improve QOL of RA patients and may possibly impact the efficacy evaluation of ASP015K.
5 and 6: Established to define the range of RA disease activity pertinent to this study.
7: Established to identify patients appropriate for evaluation using the classification criteria for functional status.
8: Established to select patients who had an inadequate response or intolerance to MTX.
9, 10: Established to choose patients who can maintain the same dosage and administration schedule for concomitant MTX or other DMARDs from before baseline and throughout the treatment period.
11: Established to ensure the integrity of the study evaluation.
Exclusion Criteria
1. Subject has received a biologic DMARD within the specified period:
Anakinra: within 28 days prior to baseline
Etanercept: within 28 days prior to baseline
Adalimumab, infliximab: within 56 days prior to baseline
Golimumab, certolizumab pegol: within 70 days prior to baseline
Abatacept, tocilizumab: within 84 days prior to baseline
Denosumab: within 150 days prior to baseline
Rituximab: within 180 days prior to baseline
2. Inadequate responder to at least 3 biologic DMARDs as determined by investigator/sub-investigator.
3. Subject has received a non-biologic DMARD listed below or other drugs used in the treatment of RA within 28 days prior to baseline.
Leflunomide is prohibited within 90 days prior to baseline. Alternatively, leflunomide is prohibited at least 28 days prior to baseline if
washout with cholestyramine for at least 17days is completed within 28 days prior to baseline. However, topical drugs other than those for
the treatment of RA may be used concomitantly.
Leflunomide
Tacrolimus
Cyclosporine
Cyclophosphamide
Azathioprine
Minocycline
Mizoribine
4. Subject has received Chinese herbal medicines listed below or other herbal drugs used in the treatment of RA within 28 days prior to
baseline.
Tripterygium wilfordii
Total glucosides of paeony
Tsuduranine
5. Subject has received tofacitinib, baricitinib or other JAK inhibitor (including other investigational drugs).
6. Subject has received intra-articular, intravenous, intramuscular, or endorectal (including suppositories for anal diseases)
corticosteroid within 28 days prior to baseline.
7. Subject has participated in any study of ASP015K and has received ASP015K or placebo.
8. Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline.
9. Subject has received plasma exchange therapy within 60 days prior to baseline.
10. Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant
(such as glucosamine sulfate, chondroitin sulfate these DMORD medicine) at the assessed joint within 28 days prior to baseline.
11. Subject has undergone surgery and has residual effects in the assessed joints at the discretion of investigator/sub-investigator, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints at the discretion of investigator/sub-investigator.
12. A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA.
13. Any of the following laboratory values during the screening test period:
Hemoglobin < 9.0 g/dL
Absolute neutrophil count < 1000/μL
Absolute lymphocyte count < 800/μL
Platelet count < 75000/μL
ALT ≥ 2 ×ULN
AST ≥ 2 × ULN
Total bilirubin (TBL) ≥ 1.5 × ULN
Estimated GFR ≤ 40 mL/min as measured by the MDRD method
β-D-glucan > ULN
Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA
quantitation, and positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by HBV-DNA quantitation from the baseline
and at every scheduled visit after initiation of study drug administration.)
Positive HCV antibody
14. Subject has a history of or concurrent active tuberculosis (TB).
*Old TB is evidenced if chest x-ray reveals pleural thickening, band-like shadow, and calcification ≥ 5mm. Chest x-ray within 90 days prior to baseline may substitute the screening test.
** T-spot or QuantiFERON Gold test is of first priority. When the result is equivocal or invalid, retest including other test methods may be allowed. If a retest is not performed, criteria for positive results will be followed. When T-spot or QuantiFERON Gold test is not feasible,
tuberculin test will be performed.
Tuberculin is defined as positive with a red spot covering an area of 10 mm or more or induration (For other regions, the requirement will
be according to the local practice, such as 5mm for enrollment in Taiwan). Tests conducted within 90 days prior to baseline may be used for diagnosis.
*** Subject must receive or have received prophylaxis with isoniazid or rifampicin. Prophylaxis will be administered for 6 to 9 months,
starting from at least 21 days prior to baseline.
15. Subject meets any of the following in terms of infections except for TB:
History of or concurrent severe herpes zoster (associated with Hunt syndrome or having ulcerative lesions) or disseminated herpes zoster
History of multiple recurrences (at least twice) of localized herpes zoster
Serious infection requiring hospitalization within 90 days prior to baseline
Subject has received intravenous antibiotics within 90 days prior to baseline. (However, prophylactic antibiotics are allowed.)
Subject with high risk of infection (e.g., subject with urinary catheter) at the discretion of investigator/sub-investigator
16. Subject has a history of or concurrent interstitial pneumonia and investigator/sub-investigator judges that it is inappropriate for the subject to participate in this study.
17. Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma).
18. Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including
influenza and pneumococcal vaccines are allowed.)
19. Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine,
pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren’s syndrome and chronic thyroiditis),
or any ongoing illness which would make the subject unsuitable for the study as determined by the investigator/sub-investigator.
20. Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria
induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.)
21. Subject has received medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to baseline. These
medications include: dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, temsirolimus, and disopyramide.
22. Subject has concurrent cardiac failure, defined as NYHA classification Class III or higher, or a history of it.
23. Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject
has QTc ≥ 500 msec at retest will be excluded) at screening.
24. Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc < 330 msec. Subject has
QTc < 330 msec at retest will be excluded) at screening.
25. Subject has a history of positive HIV infection.
26. Subject is a woman who is pregnant or might be pregnant, is nursing, wishes to conceive for a period running from the time informed
consent is given within 60 days after end of treatment, or for whom the possibility of pregnancy cannot be ruled out as a result of the
serum pregnancy test given at the time of screening.
27. Subject is a man who cannot practice at least 2 types of contraception from the time of informed consent to 90 days after end of
treatment, or subject is a woman with childbearing potential who cannot practice at least 2 types of contraception from the time of informed consent to 60 days after end of treatment.
28. Male subject who do not agree not to donate sperm starting at informed consent and through the treatment period and for at least 90 days after final study drug administration. Female subject who do not agree not to donate ova starting at informed consent through the treatment period and for 60 days after final study drug administration.
29. The subject has been judged unsuitable to participate in the study for other reasons by the investigator/sub-investigator.
30. The subject has a history or complication of lymphatic diseases such as lymphoproliferative disorder, lymphoma, and leukemia.
[Rationale for exclusion criteria]
1, 3, 4, 5, 6, 7 and 8: Established to eliminate confounding factors affecting evaluation.
2, 9, 10, 11 and 12: Established to eliminate confounding factors affecting efficacy evaluation.
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 and 30: Established out of safety concerns.
24: The QTc criterion is quoted from Expert Consensus [Silvia G. et al, 2013] of HRS/EHRA/APHRS.
29: Established in anticipation for a case where the investigator/sub-investigator judges a patient to be inappropriate for participation in the study.
Anakinra: within 28 days prior to baseline
Etanercept: within 28 days prior to baseline
Adalimumab, infliximab: within 56 days prior to baseline
Golimumab, certolizumab pegol: within 70 days prior to baseline
Abatacept, tocilizumab: within 84 days prior to baseline
Denosumab: within 150 days prior to baseline
Rituximab: within 180 days prior to baseline
2. Inadequate responder to at least 3 biologic DMARDs as determined by investigator/sub-investigator.
3. Subject has received a non-biologic DMARD listed below or other drugs used in the treatment of RA within 28 days prior to baseline.
Leflunomide is prohibited within 90 days prior to baseline. Alternatively, leflunomide is prohibited at least 28 days prior to baseline if
washout with cholestyramine for at least 17days is completed within 28 days prior to baseline. However, topical drugs other than those for
the treatment of RA may be used concomitantly.
Leflunomide
Tacrolimus
Cyclosporine
Cyclophosphamide
Azathioprine
Minocycline
Mizoribine
4. Subject has received Chinese herbal medicines listed below or other herbal drugs used in the treatment of RA within 28 days prior to
baseline.
Tripterygium wilfordii
Total glucosides of paeony
Tsuduranine
5. Subject has received tofacitinib, baricitinib or other JAK inhibitor (including other investigational drugs).
6. Subject has received intra-articular, intravenous, intramuscular, or endorectal (including suppositories for anal diseases)
corticosteroid within 28 days prior to baseline.
7. Subject has participated in any study of ASP015K and has received ASP015K or placebo.
8. Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline.
9. Subject has received plasma exchange therapy within 60 days prior to baseline.
10. Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant
(such as glucosamine sulfate, chondroitin sulfate these DMORD medicine) at the assessed joint within 28 days prior to baseline.
11. Subject has undergone surgery and has residual effects in the assessed joints at the discretion of investigator/sub-investigator, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints at the discretion of investigator/sub-investigator.
12. A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA.
13. Any of the following laboratory values during the screening test period:
Hemoglobin < 9.0 g/dL
Absolute neutrophil count < 1000/μL
Absolute lymphocyte count < 800/μL
Platelet count < 75000/μL
ALT ≥ 2 ×ULN
AST ≥ 2 × ULN
Total bilirubin (TBL) ≥ 1.5 × ULN
Estimated GFR ≤ 40 mL/min as measured by the MDRD method
β-D-glucan > ULN
Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA
quantitation, and positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by HBV-DNA quantitation from the baseline
and at every scheduled visit after initiation of study drug administration.)
Positive HCV antibody
14. Subject has a history of or concurrent active tuberculosis (TB).
*Old TB is evidenced if chest x-ray reveals pleural thickening, band-like shadow, and calcification ≥ 5mm. Chest x-ray within 90 days prior to baseline may substitute the screening test.
** T-spot or QuantiFERON Gold test is of first priority. When the result is equivocal or invalid, retest including other test methods may be allowed. If a retest is not performed, criteria for positive results will be followed. When T-spot or QuantiFERON Gold test is not feasible,
tuberculin test will be performed.
Tuberculin is defined as positive with a red spot covering an area of 10 mm or more or induration (For other regions, the requirement will
be according to the local practice, such as 5mm for enrollment in Taiwan). Tests conducted within 90 days prior to baseline may be used for diagnosis.
*** Subject must receive or have received prophylaxis with isoniazid or rifampicin. Prophylaxis will be administered for 6 to 9 months,
starting from at least 21 days prior to baseline.
15. Subject meets any of the following in terms of infections except for TB:
History of or concurrent severe herpes zoster (associated with Hunt syndrome or having ulcerative lesions) or disseminated herpes zoster
History of multiple recurrences (at least twice) of localized herpes zoster
Serious infection requiring hospitalization within 90 days prior to baseline
Subject has received intravenous antibiotics within 90 days prior to baseline. (However, prophylactic antibiotics are allowed.)
Subject with high risk of infection (e.g., subject with urinary catheter) at the discretion of investigator/sub-investigator
16. Subject has a history of or concurrent interstitial pneumonia and investigator/sub-investigator judges that it is inappropriate for the subject to participate in this study.
17. Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma).
18. Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including
influenza and pneumococcal vaccines are allowed.)
19. Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine,
pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren’s syndrome and chronic thyroiditis),
or any ongoing illness which would make the subject unsuitable for the study as determined by the investigator/sub-investigator.
20. Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria
induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.)
21. Subject has received medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to baseline. These
medications include: dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, temsirolimus, and disopyramide.
22. Subject has concurrent cardiac failure, defined as NYHA classification Class III or higher, or a history of it.
23. Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject
has QTc ≥ 500 msec at retest will be excluded) at screening.
24. Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc < 330 msec. Subject has
QTc < 330 msec at retest will be excluded) at screening.
25. Subject has a history of positive HIV infection.
26. Subject is a woman who is pregnant or might be pregnant, is nursing, wishes to conceive for a period running from the time informed
consent is given within 60 days after end of treatment, or for whom the possibility of pregnancy cannot be ruled out as a result of the
serum pregnancy test given at the time of screening.
27. Subject is a man who cannot practice at least 2 types of contraception from the time of informed consent to 90 days after end of
treatment, or subject is a woman with childbearing potential who cannot practice at least 2 types of contraception from the time of informed consent to 60 days after end of treatment.
28. Male subject who do not agree not to donate sperm starting at informed consent and through the treatment period and for at least 90 days after final study drug administration. Female subject who do not agree not to donate ova starting at informed consent through the treatment period and for 60 days after final study drug administration.
29. The subject has been judged unsuitable to participate in the study for other reasons by the investigator/sub-investigator.
30. The subject has a history or complication of lymphatic diseases such as lymphoproliferative disorder, lymphoma, and leukemia.
[Rationale for exclusion criteria]
1, 3, 4, 5, 6, 7 and 8: Established to eliminate confounding factors affecting evaluation.
2, 9, 10, 11 and 12: Established to eliminate confounding factors affecting efficacy evaluation.
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 and 30: Established out of safety concerns.
24: The QTc criterion is quoted from Expert Consensus [Silvia G. et al, 2013] of HRS/EHRA/APHRS.
29: Established in anticipation for a case where the investigator/sub-investigator judges a patient to be inappropriate for participation in the study.
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
575 participants
