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

NCT00106184 | Completed Phase 2 Results DMC

• 3 other identifiers: N01 AR0422735R01AR061298-02HHSN26420042273C
• Study Type: interventional
• Target: 200
• Locations: 4 countries
• Sites: 31

Brief Summary

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.

Conditions

Myositis; Dermatomyositis; Polymyositis; Juvenile Dermatomyositis

Keywords

rituximab; myositis; dermatomyositis; polymyositis; refractory; Juvenile Dermatomyositis

Outcome Measures

Primary Outcomes (1)

• Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients

  The Definition of Improvement for both adult and pediatric patients will be: 3 of any of the 6 core set measures improved by ≥ 20%, with no more than 2 of the core set measures worsening by ≥25% (worsening measure cannot include the MMT) at two consecutive visits. Of note, the MMT could not be one of the worsening measures. Core Set Measures Included: 1. Manual Muscle Testing (MMT)- Muscle Strength 2. Physician Global Disease Activity VAS Score 3. Health Assessment Questionnaire Index Score - Physical Function 4. Patient Global Assessment of Disease Activity VAS score 5. Extramuscular Activity - Myositis Disease Activity Assessment Tool 6. 2 or more elevated muscle enzymes (Aldolase, CK, AST, ALT, and LDH)

  Week 44 of treatment phase

Secondary Outcomes (2)

• Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8

  Week 8 of the treatment phase

• 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])

  Week 44 of treatment phase

Study Arms (6)

Adult Study Group 1

EXPERIMENTAL

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; Drug: Placebo

Adult Study Group 2

EXPERIMENTAL

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; Drug: Placebo

Adult Study Group 3

EXPERIMENTAL

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; Drug: Placebo

Adult Study Group 4

EXPERIMENTAL

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; Drug: Placebo

JDM Study Group 1

EXPERIMENTAL

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; Drug: Placebo

JDM Study Group 2

EXPERIMENTAL

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; Drug: Placebo

Interventions

Rituximab DRUG

Treatment Group A - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum does of 1 gram at Weeks 8 and 9

Also known as: Rituxan

Adult Study Group 1; Adult Study Group 2; Adult Study Group 3; Adult Study Group 4; JDM Study Group 1; JDM Study Group 2

Placebo DRUG

Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1

Adult Study Group 1; Adult Study Group 2; Adult Study Group 3; Adult Study Group 4; JDM Study Group 1; JDM Study Group 2

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (Manual Muscle Test) 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:
• An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
• If MMT (Manual Muscle Test) 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Genentech, Inc.: collaborator
• Biogen: collaborator

Study Sites (31)

University of Alabama Arthritis Intervention Program (Adult Site)

Birmingham, Alabama, 35294, United States

Location

Phoenix Neurological Associates, LTD (Adult Site)

Phoenix, Arizona, 85006, United States

Location

Cedars-Sinai Medical Center (Adult Site)

Los Angeles, California, 90048, United States

Location

Stanford University (Adult Site)

Stanford, California, 94305, United States

Location

Stanford University (Pediatric Site)

Stanford, California, 94305, United States

Location

University of Miami School of Medicine (Adult Site)

Miami, Florida, 33136, United States

Location

Miami Children's Hospital (Pediatric Site)

Miami, Florida, 33155, United States

Location

University of Kansas Medical Center (Adult Site)

Kansas City, Kansas, 66160, United States

Location

Kentucky Clinic (Adult Site)

Lexington, Kentucky, 40536, United States

Location

National Institute of Health (Adult Site)

Bethesda, Maryland, 20892, United States

Location

National Institute of Health (Pediatric Site)

Bethesda, Maryland, 20892, United States

Location

Children's Hospital of Boston (Pediatric Site)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center (Adult Site)

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System (Adult Site)

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University (Adult and Pediatric Site)

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic (Adult Site)

Rochester, Minnesota, 55905, United States

Location

Mayo Clinic (Pediatric Site)

Rochester, Minnesota, 55905, United States

Location

North Shore Long Island Jewish Health System (Adult Site)

Lake Success, New York, 11042, United States

Location

Hospital for Special Surgery (Adult Site)

New York, New York, 10021, United States

Location

Duke University Medical Center (Pediatric Site)

Durham, North Carolina, 27710, United States

Location

Cincinnati's Children's Hospital (Pediatric Site)

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia (Pediatric Site)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania (Adult Site)

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh (Pediatric Site)

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh / UPMC (Adult Site)

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Texas Southwestern Medical Center (Adult)

Dallas, Texas, 75390-8884, United States

Location

Medical College of Wisconsin / Froedtert Memorial Luthern Hospital (Adult Site)

Milwaukee, Wisconsin, 53226, United States

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Hospital for Sick Children (Pediatric Site)

Toronto, Ontario, M5G 1X8, Canada

Location

Institute of Rheumatology

Prague, Czechia

Location

Karolinska Institute

Stockholm, Sweden

Location

Related Publications (3)

• Feldman B, Wang E, Willan A, Szalai JP. The randomized placebo-phase design for clinical trials. J Clin Epidemiol. 2001 Jun;54(6):550-7. doi: 10.1016/s0895-4356(00)00357-7.

  PMID: 11377114 BACKGROUND

• Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 2005 Feb;52(2):601-7. doi: 10.1002/art.20849.

  PMID: 15692974 BACKGROUND

• Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE; RIM Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.

  PMID: 23124935 RESULT

Related Links

• Click here for the Myositis Association Web site
• Click here for the NIH Clinical Center (sub-study)

MeSH Terms

Conditions

Myositis; Dermatomyositis; Polymyositis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

There was an overestimate of the rapidity of the rituximab response and an underestimate of DOI in those receiving placebo.

Results Point of Contact

• Title: Chester V. Oddis, MD
• Organization: University of Pittsburgh

cvo5@pitt.edu

412-383-8861

Study Officials

• Chester V. Oddis, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Ann M. Reed, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor of Medicine, University of Pittsburgh, Division of Rheumatology and Clinical Immunology

Study Record Dates

• First Submitted: March 21, 2005
• First Posted: March 22, 2005
• Study Start: March 1, 2006
• Primary Completion: February 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 4, 2015
• Results First Posted: March 4, 2015

Record last verified: 2015-03

Locations

US (27); CA (2); CZ (1); SE (1)