A Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who Have Not Adequately Responded to One or More Standard-of-care Treatments

Dermatomyositis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03981744
• Other study ID #: CR108618
• Secondary ID: CNTO1275DMY3001
• Status: Terminated
• Phase: Phase 3
• Start date: July 26, 2019
• Est. completion date: July 12, 2022

Study information

• Verified date: November 2023
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: July 12, 2022
• Est. primary completion date: January 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Dermatomyositis
• Polymyositis

Intervention

Drug:
• Ustekinumab 6 mg/kg
Participants will receive body weight-range based IV dosing of 6 mg/kg of ustekinumab at Week 0 in Group 1 and at Week 24 in Group 2.
• Ustekinumab 90 mg
Participants will receive ustekinumab 90 mg SC at Week 8 and every 8 Weeks (q8w) through Week 72 in Group 1 and q8w Week 32 through Week 72 in Group 2.
• Placebo IV
Participants will receive IV dosing of placebo at Week 24 in Group 1 and at Week 0 in Group 2.
• Placebo SC
Participants will receive SC dosing of placebo at Weeks 8,16 and 24.

Locations

Country	Name	City	State
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-Ku
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Shinko Hospital	Hyogo
Japan	Tokai University Hospital	Isehara
Japan	Kagoshima University Hospital	Kagoshima City
Japan	St.Marianna University Hospital	Kanagawa
Japan	National Hospital Organization Osaka Minami Medical Center	Kawachi-Nagano
Japan	Hospital of the University of Occupational and Environmental Health	Kita-kyushu
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kurashiki Central Hospital	Kurashiki
Japan	Shinshu University Hospital	Matsumoto
Japan	Minaminagano Medical Center Shinonoi General Hospital	Nagano
Japan	Nagasaki University Hospital	Nagasaki-shi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Okayama City General Medical Center Okayama City Hospital	Okayama
Japan	Saga University Hospital	Saga
Japan	Kitasato University Hospital	Sagamihara
Japan	Sakai City Medical Center	Sakai City
Japan	Tohoku Medical And Pharmaceutical University Hospital	Sendai
Japan	Tohoku University Hospital	Sendai-shi
Japan	Dokkyo Medical University Hospital	Shimotsuga-gun
Japan	Juntendo University Hospital	Tokyo
Japan	National Center for Global Health and Medicine	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	The Jikei University Hospital	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	Yokohama Rosai Hospital	Yokohama

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved Minimal Improvement in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at 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]).	Week 24
Secondary	Change From Baseline in Functional Index-2 (FI-2) at 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.	Baseline, Week 24
Secondary	Percentage of Participants Who Experienced Disease Worsening Up to Week 24 Based on Consensus Criteria for Worsening	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.	Up to Week 24
Secondary	Change From Baseline in Manual Muscle Testing (MMT)-8 Score at 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.	Baseline, Week 24
Secondary	Change From Baseline in Physician Global Activity (PhGA) at 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.	Baseline, Week 24
Secondary	Change From Baseline in Extramuscular Assessment by Myositis Disease Activity Assessment Tool (MDAAT) at 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.	Baseline, Week 24
Secondary	Change From Baseline in Muscle Enzyme Levels at Week 24	Change from baseline in muscle enzyme levels (creatine kinase, lactate dehydrogenase) at Week 24 was reported.	Baseline, Week 24