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

NCT00774462 | Completed Phase 2

• 1 other identifier: P051204
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The traditional treatment of inflammatory myopathies (IM) and generalized myasthenia gravis (MG) is immunosuppressive therapy, usually beginning with corticosteroids. However, up to 70% of treated patients show an incomplete response, including 10 - 30% who are unresponsive. Corticosteroids and other immunosuppressive therapies presented also many side effects. We propose to evaluate in a pilot, open, prospective, multicentric, phase II study, the interest of rituximab in the treatment of patients with primary IM associated with specific AAb (anti-synthetase and anti-SRP AAbs), or MG (with anti-AchR AAbs), refractory to conventional therapies. Twenty fourth patients with primary IM (12 with anti-synthetase, 12 with anti-SRP AAbs), and 12 with MG will be included in the study.

Conditions

Myositis; Myasthenia Gravis

Keywords

Myositis; Anti-synthetase; Anti-SRP; Myasthenia gravis; Rituximab

Outcome Measures

Primary Outcomes (1)

• Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)

  at month 12

Secondary Outcomes (6)

• - Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)

  at day 21 and month 12

• - Improvement of functional scale score (SF36)

  at day 21 and month 12

• - Decrease of CK levels

  at day 21 and month 12

• - Evolution of auto-antibody titers

  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

  at day 21 and month 12

Study Arms (1)

1

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 1000 mg intravenous, 2 times, 2 weeks apart and 1000 mg 6 months after the last injection

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For myositis III. Idiopathic myositis
• Myositis as defined by the 119th ENMC:
• Proximal myopathy with weakness
• Subacute or insidious onset over 18 years
• Myogenic syndrome on EMG (optional)
• Muscle fibre necrosis and regeneration and/or inflammatory cell infiltrate on muscular biopsy
• Specific AAbs : anti-synthetases (anti-JO1, anti-PL7, or anti-PL12), or anti-SRP.
• For myasthenia III. Generalised MG
• Generalised seropositive MG as defined by the Texas Clinical Classification System:
• Extraocular muscle weakness quantified with MG muscle score (MMS), whose inter and inter observer reproducibility has been demonstrated \[44\].

You may not qualify if:

• Other muscular diseases, such as:
• Macrophagic myofasciitis
• Inherited myopathies
• Secondary IM to one other connective tissue disorders
• Systemic scleroderma (ARA and/or "LEROY AND MEDSGER" criteria)
• Sjögren's syndrome (European criteria)
• Systemic lupus erythematosus (ACR criteria)
• Rheumatoid arthritis (ACR criteria)
• Mixed connective tissue disease (ACR criteria)
• Other myasthenic syndrome, such as:
• Non generalised, ocular MG
• Lambert Eaton syndrome
• MG associated with malignant thymoma
• Inherited myasthenic syndrome
• Cancer (or cancer-associated myositis)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Service de Médecine Interne 1 / Groupe Hospitalier Pitié-Salpêtrière

Paris, 75651 Cedex 13, France

Location

Related Publications (1)

• Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, Jouen F, Jacquot S, Mariampillai K, Musset L, Grenier P, Devilliers H, Hij A, Boyer O, Herson S, Benveniste O. Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial. PLoS One. 2015 Nov 5;10(11):e0133702. doi: 10.1371/journal.pone.0133702. eCollection 2015.

  PMID: 26539981 DERIVED

MeSH Terms

Conditions

Myositis; Myasthenia Gravis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Olivier BENVENISTE, PUPH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2008
• First Posted: October 17, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 11, 2012

Record last verified: 2007-12

Locations

FR (1)