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

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

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).

Study Overview

• Status: Terminated
• Conditions: Dermatomyositis; Polymyositis
• Intervention / Treatment: Drug: Ustekinumab 6 mg/kg; Drug: Ustekinumab 90 mg; Drug: Placebo IV; Drug: Placebo SC

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyo-Ku, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Hyogo, Japan, 651-0072
    • Shinko Hospital
  • Isehara, Japan, 259-1193
    • Tokai University Hospital
  • Kagoshima City, Japan, 890-8544
    • Kagoshima University Hospital
  • Kanagawa, Japan, 216-8511
    • St.Marianna University Hospital
  • Kawachi-Nagano, Japan, 586-8521
    • National Hospital Organization Osaka Minami Medical Center
  • Kita-kyushu, Japan, 807-8555
    • Hospital of the University of Occupational and Enviromental Health
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kurashiki, Japan, 710-8602
    • Kurashiki Central Hospital
  • Matsumoto, Japan, 390-8621
    • Shinshu University Hospital
  • Nagano, Japan, 388-8004
    • Minaminagano Medical Center Shinonoi General Hospital
  • Nagasaki-shi, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya-shi, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Okayama, Japan, 700-8557
    • Okayama City General Medical Center Okayama City Hospital
  • Saga, Japan, 849-8501
    • Saga University Hospital
  • Sagamihara, Japan, 252-0375
    • Kitasato University Hospital
  • Sakai City, Japan, 593-8304
    • Sakai City Medical Center
  • Sendai, Japan, 983-8512
    • Tohoku Medical and Pharmaceutical University Hospital
  • Sendai-shi, Japan, 980-8574
    • Tohoku University Hospital
  • Shimotsuga-gun, Japan, 321-0293
    • Dokkyo Medical University Hospital
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan, 162-8655
    • National Center for Global Health and Medicine
  • Toon, Japan, 791-0295
    • Ehime University Hospital
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Tsukuba, Japan, 305-8576
    • University of Tsukuba Hospital
  • Ube, Japan, 755-8505
    • Yamaguchi University Hospital
  • Yokohama, Japan, 222-0036
    • Yokohama Rosai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Ustekinumab + Placebo; 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.	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.; Other Names: STELARA; Drug: 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.; Other Names: STELARA; Drug: Placebo IV; Participants will receive IV dosing of placebo at Week 24 in Group 1 and at Week 0 in Group 2.
Placebo Comparator: Group 2: Placebo + Ustekinumab; 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.	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.; Other Names: STELARA; Drug: 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.; Other Names: STELARA; Drug: Placebo IV; Participants will receive IV dosing of placebo at Week 24 in Group 1 and at Week 0 in Group 2.; Drug: Placebo SC; Participants will receive SC dosing of placebo at Weeks 8,16 and 24.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who achieve Minimal Improvement in International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at Week 24	Minimal improvement is defined as IMACS TIS greater than or equal to (>=)20 in participants with polymyositis (PM)/ dermatomyositis (DM). The criteria use the 6 IMACS core set measures: Global Activity-VAS, Patient Global Activity-VAS, MMT-8, Muscle Enzymes, Extramuscular Assessment (MDAAT), and Functional Assessment (HAQ-DI). The absolute percentage change in each measure with varying weights is combined to obtain a Total Improvement Score (TIS) on a scale of 0 to 100. Higher score indicates greater improvement.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Functional Index-2 (FI-2) Score at Week 24	Change from baseline in functional Index-2 at Week 24 will be reported. The FI-2 is a functional outcome developed for participants with adult PM or DM to assess muscle endurance in 7 muscle groups. Each muscle group is scored as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions depending on muscle group. The FI-2 is performed unilaterally, preferably on the participant's dominant side for muscle groups of shoulder, hip, and step test. The FI-2 has been validated as to content and construct validity and intra- and interrater reliability. The score ranges from 0-60 or 0-120 depending on the muscle group. Higher score indicates better muscle endurance.	Baseline and Week 24
Percentage of Participants who Experience Disease Worsening Through Week 24 Based on Consensus Criteria for Worsening	Percentage of participants who experience disease worsening through Week 24 based on consensus criteria for worsening will be reported. Criteria for disease worsening in a clinical trial were based on international consensus guideline developed by the IMACS. The worsening of disease is defined as 1 of the following criteria: Worsening of the Physician Global Activity by greater than or equal to (>=2) centimeter (cm) on a 10-cm 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 activity measures by >= 30% from baseline.	Through Week 24
Change from Baseline in Manual Muscle Testing (MMT)-8 Score at Week 24	Change from baseline in MMT-8 score at Week 24 will be reported. Manual Muscle Testing is a partially validated tool to assess muscle strength. MMT-8 score ranges from 0-80, where maximal score is sum of scores from 8 muscle groups and each muscle group is scored on a 0 to 10-point scale. Higher score indicates greater muscle strength, that is, less impairment of muscle.	Baseline and Week 24
Change from Baseline in Physician Global Activity (PhGA) at Week 24	Change from baseline in physician global activity at Week 24 will be reported. Physician Global Activity is 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 10 cm VAS, where 0 cm= no evidence of disease activity and 10 cm= extremely active or severe disease activity.	Baseline and Week 24
Change from Baseline in Extramuscular Assessment (Myositis Disease Activity Assessment Tool [MDAAT]-Extramuscular Global Assessment) Score at Week 24	Change from baseline in extramuscular assessment (myositis disease activity assessment tool [MDAAT]-Extramuscular Global Assessment) Score at Week 24 will be reported. MDAAT is scored on a 10 cm scale ranging from 0-10 cm where, 0 cm = absent and 10 cm = maximum disease activity.	Baseline and Week 24
Change from Baseline in Muscle Enzymes at Week 24	Change from baseline in muscle enzyme like creatine kinase [CK], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], and aldolase) at Week 24 measured as units/liter will be reported.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Actual): January 24, 2022
• Study Completion (Actual): July 12, 2022

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Dermatomyositis; Polymyositis; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR108618; CNTO1275DMY3001 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No