A Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who Have Not Adequately Responded to One or More Standard-of-care Treatments
- Conditions
- PolymyositisDermatomyositis
- Interventions
- Registration Number
- NCT03981744
- Lead Sponsor
- Janssen Pharmaceutical K.K.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 51
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Ustekinumab Ustekinumab 90 mg 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. Group 1: Ustekinumab Ustekinumab 6 mg/kg 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. Group 1: Ustekinumab Placebo IV 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. Group 2: Placebo Ustekinumab 6 mg/kg 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. Group 2: Placebo Ustekinumab 90 mg 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. Group 2: Placebo Placebo IV 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. Group 2: Placebo Placebo SC 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Minimal Improvement in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at Week 24 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 \[improvement \>=60\]).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Manual Muscle Testing (MMT)-8 Score at Week 24 Baseline, Week 24 Change from baseline in MMT-8 score at Week 24 was reported. Manual Muscle Testing was a partially validated tool to assess muscle strength. MMT-8 total score ranged from 0-80, where maximal score was sum of scores from 8 muscle groups (Deltoid middle \[left/right\], Biceps brachii \[left/right\], Gluteus maximus \[left/right\], Gluteus medius \[left/right\], Quadriceps \[left/right\], Wrist extensors \[left/right\], Ankle dorsiflexors \[left/right\], Neck flexors \[axial\]) and each muscle group was scored on a 0 to 10-point scale. The sides (right or left) used for calculating the total score. Higher score indicated greater muscle strength, that is, less impairment of muscle.
Change From Baseline in Functional Index-2 (FI-2) at Week 24 Baseline, Week 24 Change from baseline in FI-2 at Week 24 was reported. The FI-2 was a functional outcome developed for participants with adult PM or DM to assess muscle endurance in 7 muscle groups (shoulder flexion \[0-60\], shoulder abduction \[0-60\], head lift \[0-60\], hip flexion \[0-60\], step test \[0-60\], heel lift \[0-120\], and toe lift \[0-120\]). Each muscle group was scored as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions depending on muscle group. The FI-2 was performed unilaterally, preferably on the participant's dominant side for muscle groups of shoulder, hip, and step test. The FI-2 score ranged from 0-60 or 0-120 depending on the muscle group. Higher score indicated better muscle endurance.
Percentage of Participants Who Experienced Disease Worsening Up to Week 24 Based on Consensus Criteria for Worsening Up to Week 24 Percentage of participants who experienced disease worsening up to Week 24 based on consensus criteria for worsening was reported. Criteria for disease worsening in a clinical trial were based on international consensus guideline developed by the IMACS. The worsening of disease was defined as 1 of the following criteria: Worsening of the Physician Global Activity by \>=2 centimeter (cm) on a 10-cm visual analogue scale (VAS) and worsening of findings of MMT-8 by \>= 20 percent (%) from baseline; worsening of MDAAT-global extramuscular organ disease activity (a composite of constitutional, cutaneous, skeletal, gastrointestinal, pulmonary, and cardiac activity) by \>=2 cm on a 10-cm VAS from baseline; worsening of any 3 of 6 IMACS core set (PhGA, PtGA, MMT-8, muscle enzymes, MDAAT, and HAQ-D) activity measures by \>= 30% from baseline.
Change From Baseline in Physician Global Activity (PhGA) at Week 24 Baseline, Week 24 Change from baseline in PhGA at Week 24 was reported. Physician Global Activity was a partially validated tool to measure the global evaluation by the physician of the participant's overall disease activity at the time of assessment using a 0-10 cm VAS, where 0 cm= no evidence of disease activity and 10 cm= extremely active or severe disease activity. Negative values indicated improvement from baseline.
Change From Baseline in Extramuscular Assessment by Myositis Disease Activity Assessment Tool (MDAAT) at Week 24 Baseline, Week 24 Change from baseline in extramuscular assessment by MDAAT at Week 24 was reported. This validated tool measure the degree of disease activity of extramuscular organ systems and muscle on a 0-10 cm VAS. Extramuscular activity ranged between 0 and 10 via VAS where, 0 cm = absent and 10 cm = maximum disease activity.
Change From Baseline in Muscle Enzyme Levels at Week 24 Baseline, Week 24 Change from baseline in muscle enzyme levels (creatine kinase, lactate dehydrogenase) at Week 24 was reported.
Trial Locations
- Locations (32)
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Shinko Hospital
🇯🇵Hyogo, Japan
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyo-Ku, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Okayama City General Medical Center Okayama City Hospital
🇯🇵Okayama, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Japan
Kagoshima University Hospital
🇯🇵Kagoshima City, Japan
Yokohama Rosai Hospital
🇯🇵Yokohama, Japan
Saga University Hospital
🇯🇵Saga, Japan
Dokkyo Medical University Hospital
🇯🇵Shimotsuga-gun, Japan
National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Ehime University Hospital
🇯🇵Toon, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba, Japan
Yamaguchi University Hospital
🇯🇵Ube, Japan
Kurashiki Central Hospital
🇯🇵Kurashiki, Japan
The Jikei University Hospital
🇯🇵Tokyo, Japan
Tokai University Hospital
🇯🇵Isehara, Japan
St.Marianna University Hospital
🇯🇵Kanagawa, Japan
Hospital of the University of Occupational and Environmental Health
🇯🇵Kita-kyushu, Japan
National Hospital Organization Osaka Minami Medical Center
🇯🇵Kawachi-Nagano, Japan
Shinshu University Hospital
🇯🇵Matsumoto, Japan
Minaminagano Medical Center Shinonoi General Hospital
🇯🇵Nagano, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya-shi, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Japan
Sakai City Medical Center
🇯🇵Sakai City, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Japan
Tohoku Medical And Pharmaceutical University Hospital
🇯🇵Sendai, Japan