Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00774462
• Date of registration: 16/10/2008
• Prospective Registration: No
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis FORCE
• Scientific title: FORCE: Rituximab (CD 20+-B Cell-depleting Monoclonal Antibody) for the Treatment of Refractory Inflammatory Myopathies With Specific Antibodies and Refractory Myasthenia Gravis
• Date of first enrolment: January 2008
• Target sample size: 30
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00774462
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Olivier BENVENISTE, PUPH
• Affiliation: Assistance Publique - Hôpitaux de Paris

Key inclusion & exclusion criteria

Inclusion Criteria:

- For myositis III. Idiopathic myositis

1. Myositis as defined by the 119th ENMC:

1. Proximal myopathy with weakness

2. Subacute or insidious onset over 18 years

3. Myogenic syndrome on EMG (optional)

4. Muscle fibre necrosis and regeneration and/or inflammatory cell infiltrate
on muscular biopsy

2. Specific AAbs : anti-synthetases (anti-JO1, anti-PL7, or anti-PL12), or
anti-SRP.

IV. Refractory to the conventional treatments Resistance to conventional
treatments is defined as an inadequate response to, or intolerable side effects
with conventional treatments, such as corticosteroids, azathioprine,
methotrexate, cyclophosphamide, cyclosporine, IgIV and/or plasma exchange. At
least one or more of these drugs or therapeutical approaches (used alone or as a
combination) must have been unsuccessfully tested before inclusion. Inadequate
response is defined as the lack of improvement and/or the degradation of
evaluation parameters (defined bellow) despite these conventional therapies,
that led to a modification or a reintroduction of treatment.

- For myasthenia III. Generalised MG

Generalised seropositive MG as defined by the Texas Clinical Classification System:

1. Extraocular muscle weakness quantified with MG muscle score (MMS), whose inter and
inter observer reproducibility has been demonstrated [44].

2. Specific AAbs : anti-AchR IV. Refractory to the conventional treatments Resistance to
conventional treatments is defined as an inadequate response to, or intolerable side
effects with conventional treatments, such as corticosteroids, azathioprine,
methotrexate, cyclophosphamide, cyclosporine, IgIV and/or plasma exchange. At least
one or more of these drugs or therapeutical approaches (used alone or as a
combination) must have been unsuccessfully tested before inclusion. Inadequate
response is defined as the lack of improvement and/or the degradation of evaluation
parameters (defined bellow) despite these conventional therapies, that led to a
modification or a reintroduction of treatment

Exclusion Criteria:

- Other muscular diseases, such as:

1. Inclusion body myositis

2. Macrophagic myofasciitis

3. Inherited myopathies

- Secondary IM to one other connective tissue disorders

1. Systemic scleroderma (ARA and/or "LEROY AND MEDSGER" criteria)

2. Sjögren's syndrome (European criteria)

3. Systemic lupus erythematosus (ACR criteria)

4. Rheumatoid arthritis (ACR criteria)

5. Mixed connective tissue disease (ACR criteria)

- Other myasthenic syndrome, such as:

1. Non generalised, ocular MG

2. Lambert Eaton syndrome

3. MG associated with malignant thymoma

4. Inherited myasthenic syndrome

- Cancer (or cancer-associated myositis)

- Age < 18 years

- Pregnancy

- HIV seropositivity

- Evolutive infection (B, C hepatitis, tuberculosis)

- Lack of approved consent



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Myasthenia Gravis

Myositis

Intervention(s)

Drug: Rituximab

Primary Outcome(s)

Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia) [Time Frame: at month 12]

Secondary Outcome(s)

- Improvement in the treatment burden defined as the possibility to decrease the dose or stop some of the drugs used at entry [Time Frame: at day 21 and month 12]

- Improvement of functional scale score (SF36) [Time Frame: at day 21 and month 12]

- Evolution of auto-antibody titers [Time Frame: at day 21 and month 12]

- Improvement of extra-muscular activity of the disease such as the level of lung involvement by pulmonary function tests [Time Frame: at day 21 and month 12]

- Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia) [Time Frame: at day 21 and month 12]

- Decrease of CK levels [Time Frame: at day 21 and month 12]

Secondary ID(s)

P051204

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Roche Pharma AG

Institut National de la Santé Et de la Recherche Médicale, France