Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM) - Rituximab in myositis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000078-65-SE
• Date of registration: 02/11/2006
• Prospective Registration: Yes
• Primary sponsor: Karolinska University Hospital
• Public title: Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM) - Rituximab in myositis
• Scientific title: Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM) - Rituximab in myositis
• Date of first enrolment: 17/01/2007
• Target sample size: 202
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000078-65
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adults with definite or probable DM or PM and pediatric patients five years of age and over with definite or probable JDM. Patients without the rash of DM will require a muscle biopsy compatible with PM as determined by an experienced muscle pathologist. In order to be enrolled with a diagnosis of refractory PM, patients’ medical information will be reviewed and the diagnosis confirmed by a 3-member Adjudication Committee. This adjudication process is necessary to exclude mimics of polymyositis.
2. A diagnosis of JDM based on an age of onset (i.e. first symptom of myositis or the rash of dermatomyositis) < 18 years of age.
3. Refractory myositis as defined by the intolerance to or an inadequate response to corticosteroids plus an adequate regimen of at least one other IS agent .
An adequate corticosteroid treatment trial is as follows:
•Adult IIM: prednisone (or an equivalent corticosteroid) at a dose of at least 60 mg/day for one month
•JDM: 1.0mg/kg/day prednisone for at least one month

4.Baseline manual muscle testing which is based on a maximum MMT-8 score of 150 (see Appendix D): 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 as listed below. 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 as listed below. OR 2) If MMT score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures as listed below
•Patient/Parent global VAS with a minimum value of 2.0cm on a 10cm scale
•MD global VAS with a minimum value of 2.0cm on a 10cm scale
•CHAQ/HAQ disability index with a minimum value of 0.25
•Elevation of at least one of the muscle enzymes [which includes creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] at a minimum level of 1.3 x the upper limit of normal.
If more than one muscle enzyme is identified as being elevated and meeting the above guidelines then the most abnormal will be selected and this enzyme will be the target enzyme followed to evaluate disease improvement or worsening.
•Global extramuscular disease activity score with a minimum value of 1.0cm on a 10cm VAS scale (this measure is the physician’s composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiac scales of the Myositis Disease Activity Assessment Tool (MDAAT) - see Appendix D
5.If on prednisone, the dose must be stable for 4 weeks prior to the screening visit (recommend = 1.0 mg/kg/day).
6.Background therapy with at least 1 non-corticosteroid immunosuppressive agent is required at a stable dose for at least 6 weeks prior to the screening visit.
•The IS agents include: methotrexate, azathioprine, cyclosporine, tacrolimus, cyclophosphamide or mycophenolate mofetil.
7.If an IS agent was discontinued prior to the screening visit then there must be a:
•4 week washout for methotrexate
•8 week washout for any other IS agent
8.If on plaquenil the dose should be stable for 8 weeks prior to Visit 1.
9.If on statin agents the dose should be stable for 8 weeks prior to Visit 1.
10.Ability of patient or parent to comple
Exclusion criteria:
1.Drug-induced myositis (myositis in patients taking medications known to induce myositis-like syndromes, including, but not limited to, statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine).
2.Use of colchicine during study participation is not allowed.
3.Juvenile polymyositis; inclusion body myositis; cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer except basal or squamous cell skin cancer or carcinoma in situ of the cervix if at least 5 years since excision
4.Myositis in overlap with another connective tissue disease (CTD) that precludes the accurate assessment of a treatment response (the 3-member committee discussed under Inclusion Criteria #1 above will also determine the eligibility of such patients with myositis and an associated CTD).
5.History of receiving a live vaccine 4 weeks prior to initiation of study treatment
6.Joint disease or other musculoskeletal condition, which precludes the ability to quantitate muscle strength.
7.Known hypersensitivity to murine proteins.
8.Concomitant illness that would prevent adequate patient assessment or in the investigators opinion pose an added risk for study participants. The clinical site investigator should consider further evaluation or consultation if clinically indicated prior to study enrollment
•recurrent or chronic infections, including HIV, hepatitis B and C
•known liver disease (i.e. cirrhosis or other conditions compromising the synthetic function of the liver)
•disorders that would preclude accurate assessment of neuromuscular function
•cardiomyopathy or arrhytmias that in the investigators opinion poses additional risk for study participants
•New York Heart Association Classification III or IV for congestive heart failure.
•psychiatric illness that precludes compliance or neuromuscular assessment
•serum creatinine > 2.0mg/dl
•IgG or IgM levels at baseline that are below the normal range (for pediatrics age adjusted normal ranges will be followed)
9.Pregnant females or nursing mothers
10.Life threatening non-myositis illness that would interfere with the patient’s ability to complete the study.
11.Known or suspected history of drug or alcohol abuse within the past 6 months as determined by the medical record or patient interview
12.Anticipated poor compliance
13.Participation in another clinical (experimental) study within 30 days of screening visit.
14.Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator unsuitable for the study.
15.Any history of receiving rituximab
16.Evidence of prior infection of Hepatitis B and Hepatitis C
17.Initiation of an exercise program within 4 weeks of screening visit or initiation of an exercise program during the study (See section 5.4 Other Restrictions)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adult polymyositis or adult dermatomyositis or juvenile dermatomyositis
MedDRA version: 8.1 Level: LLT Classification code 10036102 Term: Polymyositis

Intervention(s)

Trade Name: Mabthera
Product Name: Mabthera
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Rituximab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: AIM #2: To assess the determinants of treatment response and disease pathogenesis in patients receiving rituximab.

Main Objective: AIM #1: To assess the efficacy of intravenous rituximab in a randomized, double blind, placebo-controlled, multicenter, phase II/III trial of refractory myositis in adults and children.

Primary end point(s): The primary endpoint of this trial is to compare the time to achieve the definition of improvement (DOI) between the two groups of rituximab-treated patients.

Secondary ID(s)

Rituximab