Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)
Condition: Myositis; Dermatomyositis; Polymyositis; Juvenile Dermatomyositis
MeSH terms: Dermatomyositis; Myositis; Polymyositis
Intervention: Rituximab; Placebo
Intervention description: 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; Treatment Group A: placebo infusion at Weeks 8 and 9
Treatment Group B: placebo infusion at Weeks 0 and 1
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 200.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No
Keywords: rituximab; myositis; dermatomyositis; polymyositis; refractory; Juvenile Dermatomyositis

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.
    

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