A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who Have Not Adequately Responded to One or More Standard-of-care Treatments
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 51
- 试验地点
- 32
- 主要终点
- Percentage of Participants Who Achieved Minimal Improvement in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of ustekinumab in participants with active polymyositis (PM)/dermatomyositis (DM) despite receiving 1 or more standard-of-care treatments (for example, glucocorticoids and/or immunomodulators).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of polymyositis (PM)/ dermatomyositis (DM) made or confirmed by a physician (such as a rheumatologist, neurologist, or dermatologist) experienced in treatment of PM/DM at least 6 weeks prior to first dose of the study drug
- •Has PM or DM which is considered active despite receiving at least 1 standard-of-care treatment by the investigator
- •Must be receiving 1 or more of the following protocol-permitted, systemic standard-of-care treatments: i) glucocorticoids, ii) 1 or 2 of the following immunomodulatory drugs: mycophenolate mofetil, azathioprine, oral methotrexate, oral tacrolimus, or oral cyclosporine A
- •Regular or as needed treatment with topical use of glucocorticoids are permitted to treat skin lesions on a stable dose for greater than or equal to (>=) 2 weeks prior to first dose of the study drug
- •Contraceptive (birth control) use by men or women should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
- •Must be medically stable on the basis of clinical laboratory tests performed at screening. If the results of the clinical laboratory tests are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant
- •Demonstrable muscle weakness at screening and Week 0 measured by the Manual Muscle Testing (MMT)-8 less than or equal to (<=)135 units
- •Demonstrable muscle weakness at screening measured by any 2 or more of the followings: (i) PhGA greater than or equal to (>=) 1.5 centimeter (cm), (ii) 1 or more muscle enzymes (Creatine kinase [CK], and aldolase) >=1.4*upper limit of normal (ULN), (iii) Myositis disease activity assessment tool (MDAAT)-Extramuscular Global Assessment >=1.5 cm
排除标准
- •Has myositis other than PM/DM, including but not limited to amyopathic dermatomyositis (ADM), clinically amyopathic DM, juvenile DM, inclusion body myositis (IBM) immune-mediated necrotizing myopathy diagnosed based on muscle biopsy findings and positive anti-SRP or anti-HMGCR antibody, drug-induced myositis, PM associated with human immunodeficiency virus (HIV), and muscular dystrophy, congenital myopathy, metabolic myopathy, and mitochondrial myopathy
- •Has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), psoriasis, or Crohn's disease
- •Has severe respiratory muscle weakness confirmed by the investigator based on the consultation with a pulmonologist and the measures of respiratory muscle strength such as maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) and/or maximal voluntary ventilation (MVV) measurements and lung capacity such as forced vital capacity (FVC). The results need to be within population appropriate normal limits
- •Has severe muscle damage (Myositis Damage Index-VAS [Muscle Damage] greater than (>) 7 centimeter [cm]), permanent weakness due to a non-IIM cause, or myositis with cardiac dysfunction
- •Has glucocorticoid-induced myopathy which the investigator considers the primary cause of muscle weakness
- •Has positive test result of anti-melanoma differentiation-associated protein 5 (MDA5) antibody (anti clinically amyopathic dermatomyositis (C-ADM)-140 antibody).
- •Has had a nontuberculous mycobacterial infection or opportunistic infection
- •Has a history of, or ongoing, chronic or recurrent infectious disease
- •Has past history of severe Interstitial lung disease (ILD) flare, severe non-infectious lung inflammation which required active intervention, or multiple relapses of these conditions
- •Presence or history of malignancy within 5 years before screening
研究组 & 干预措施
Group 1: Ustekinumab
Participants will receive body weight-range based IV dosing of approximately 6 milligram per kilogram (mg/kg) of ustekinumab at Week 0 followed by ustekinumab 90 milligram (mg) subcutaneously (SC) at Week 8 and every 8 Weeks (q8w) administrations through Week 72. At Week 24, participants will receive IV dosing of placebo.
干预措施: Ustekinumab 6 mg/kg (Drug)
Group 1: Ustekinumab
Participants will receive body weight-range based IV dosing of approximately 6 milligram per kilogram (mg/kg) of ustekinumab at Week 0 followed by ustekinumab 90 milligram (mg) subcutaneously (SC) at Week 8 and every 8 Weeks (q8w) administrations through Week 72. At Week 24, participants will receive IV dosing of placebo.
干预措施: Ustekinumab 90 mg (Drug)
Group 1: Ustekinumab
Participants will receive body weight-range based IV dosing of approximately 6 milligram per kilogram (mg/kg) of ustekinumab at Week 0 followed by ustekinumab 90 milligram (mg) subcutaneously (SC) at Week 8 and every 8 Weeks (q8w) administrations through Week 72. At Week 24, participants will receive IV dosing of placebo.
干预措施: Placebo IV (Drug)
Group 2: Placebo
Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations at Weeks 8,16 and 24. At Week 24, participants will receive body weight-range based IV dosing of approximately 6 mg/kg of ustekinumab, followed by ustekinumab 90 mg SC q8w administrations Week 32 through Week 72.
干预措施: Ustekinumab 6 mg/kg (Drug)
Group 2: Placebo
Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations at Weeks 8,16 and 24. At Week 24, participants will receive body weight-range based IV dosing of approximately 6 mg/kg of ustekinumab, followed by ustekinumab 90 mg SC q8w administrations Week 32 through Week 72.
干预措施: Ustekinumab 90 mg (Drug)
Group 2: Placebo
Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations at Weeks 8,16 and 24. At Week 24, participants will receive body weight-range based IV dosing of approximately 6 mg/kg of ustekinumab, followed by ustekinumab 90 mg SC q8w administrations Week 32 through Week 72.
干预措施: Placebo IV (Drug)
Group 2: Placebo
Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations at Weeks 8,16 and 24. At Week 24, participants will receive body weight-range based IV dosing of approximately 6 mg/kg of ustekinumab, followed by ustekinumab 90 mg SC q8w administrations Week 32 through Week 72.
干预措施: Placebo SC (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Minimal Improvement in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at Week 24
时间窗: Week 24
Minimal improvement was defined as IMACS TIS greater than or equal to (\>=) 20 in participants with polymyositis (PM)/dermatomyositis (DM). Criteria used the 6 IMACS core set measures: physician global activity (PhGA)(0-10), patient global activity (PtGA)(0-10), manual muscle testing-8 (MMT-8)(0-80), muscle enzymes (creatine kinase, Aldolase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase), extramuscular assessment of myositis disease activity assessment tool (MDAAT)(0-10), and health assessment questionnaire disability index (HAQ-DI)(0-3). Absolute percent change in each core set measure was calculated as final value minus baseline value divided by range\*100. Total improvement score was calculated by sum of 6 core set improvement scores. Total improvement score ranged from 0 to 100 where higher scores indicated greater improvement. This was categorized into 3 categories (minimal \[improvement \>=20\], moderate \[improvement \>=40\] and major \[improvement \>=60\]).
次要结局
- Change From Baseline in Manual Muscle Testing (MMT)-8 Score at Week 24(Baseline, Week 24)
- Change From Baseline in Functional Index-2 (FI-2) at Week 24(Baseline, Week 24)
- Percentage of Participants Who Experienced Disease Worsening Up to Week 24 Based on Consensus Criteria for Worsening(Up to Week 24)
- Change From Baseline in Physician Global Activity (PhGA) at Week 24(Baseline, Week 24)
- Change From Baseline in Extramuscular Assessment by Myositis Disease Activity Assessment Tool (MDAAT) at Week 24(Baseline, Week 24)
- Change From Baseline in Muscle Enzyme Levels at Week 24(Baseline, Week 24)