Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Genentech
Biogen Idec
Information provided by:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:
NCT00106184
First received: March 21, 2005
Last updated: July 28, 2010
Last verified: April 2009
  Purpose

Rituximab is a man-made antibody used to treat certain types of cancer. This study will determine whether rituximab is an effective treatment for adult and pediatric patients with dermatomyositis or polymyositis.

Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first) will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The proportion of patients improved at Week 8 of the treatment phase will be significantly greater in Group A than in Group B.


Condition Intervention Phase
Myositis
Dermatomyositis
Polymyositis
Juvenile Dermatomyositis
Drug: Rituximab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)

Resource links provided by NLM:


Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:
  • Comparison between the two groups of IIM patients in their time to achieve improvement [ Time Frame: Week 44 of treatment phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rates (proportion of improved patients) between Groups A (rituximab-treated) and B (placebo-treated) [ Time Frame: Week 8 of the treatment phase ] [ Designated as safety issue: No ]
  • 20% improvement in Manual Muscle Testing (MMT) over baseline on two consecutive time points (muscle is the primary organ of involvement, and MMT is the one objective measurement of the Definition of Improvement [DOI]) [ Time Frame: Week 44 of treatment phase ] [ Designated as safety issue: No ]

Estimated Enrollment: 202
Study Start Date: March 2006
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adult Study Group 1
Refractory adult polymyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Experimental: Adult Study Group 2
Refractory adult polymyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Experimental: Adult Study Group 3
Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Experimental: Adult Study Group 4
Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Experimental: JDM Study Group 1
Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Experimental: JDM Study Group 2
Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Drug: Rituximab
Treatment Group A - intravenous rituximab 750mg/m2 BSA up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA up to a maximum does of 1 gram at Weeks 8 and 9
Other Name: Rituxan
Drug: Placebo

Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults with definite or probable dermatomyositis or polymyositis and pediatric patients five years of age and over with definite or probable juvenile dermatomyositis (JDM) by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e., first symptom of myositis or dermatomyositis rash) is less 18 years of age
  • Refractory myositis, defined by intolerance to or inadequate response to corticosteroids plus an adequate regime of at least one other immunosuppressive agent. Intolerance is defined as side effects that require discontinuation of the medication or an underlying condition that precludes further use of the medication.
  • Baseline manual muscle testing which is based on a maximum MMT-8 score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.

Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the following criteria:

  1. An MMT-8 score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.

    OR

  2. If MMT score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures.

    • Background therapy with at least 1 non-corticosteroid immunosuppressive agent at a stable dose for at least 6 weeks prior to screening
    • Able and willing to complete self-report questionnaires. Parents of pediatric participants will be required to complete the questionnaires on behalf of their children.
    • Willing to use acceptable forms of contraception for the duration of the study for patients of reproductive potential.
    • Parent willing to provide informed consent, if applicable
    • Willing to forgo immunization with a live vaccine for the duration of the study

Exclusion Criteria:

  • Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by taking medications known to induce myositis-like syndromes, including but not limited to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
  • Juvenile polymyositis
  • Inclusion body myositis
  • Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in situ of the cervix are not excluded, if it has been at least 5 years since excision.
  • Myositis in overlap with another connective tissue disease that may preclude the accurate assessment of a treatment response
  • Live viral vaccine within 4 weeks prior to study entry
  • Any joint disease or other musculoskeletal condition that may interfere with muscle strength testing
  • Known hypersensitivity to mouse proteins
  • Any concomitant or life-threatening non-myositis illness that, in the opinion of the investigator, may interfere with the study
  • Known or suspected history of drug or alcohol abuse within the last 6 months prior to study entry, as determined by medical record or patient interview
  • Anticipated poor compliance with study requirements
  • Participation in another clinical trial within 30 days prior to screening
  • Any history or evidence of any severe illness or other condition that, in the opinion of the investigator, may interfere with the study
  • Previously received rituximab
  • Evidence of prior infection with hepatitis B or hepatitis C virus
  • Initiation of an exercise program within 4 weeks of screening OR initiation of an exercise program during the study
  • Consumed any creatine-containing, over-the-counter products in the form of dietary supplements 30 days prior to screening visit and for the duration of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00106184

  Show 31 Study Locations
Sponsors and Collaborators
Genentech
Biogen Idec
Investigators
Principal Investigator: Chester V. Oddis, MD University of Pittsburgh
Principal Investigator: Ann M. Reed, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chester V. Oddis, Professor of Medicine, University of Pittsburgh, Division of Rheumatology and Clinical Immunology
ClinicalTrials.gov Identifier: NCT00106184     History of Changes
Obsolete Identifiers: NCT00393237
Other Study ID Numbers: N01 AR042273, HHSN26420042273C
Study First Received: March 21, 2005
Last Updated: July 28, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
rituximab
myositis
dermatomyositis
polymyositis
refractory
Juvenile Dermatomyositis

Additional relevant MeSH terms:
Dermatomyositis
Myositis
Polymyositis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Connective Tissue Diseases
Skin Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014