MyositisPhase 2FORCENCT00774462
Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis
A Phase 2 study testing Rituximab in people with Myositis and Myasthenia Gravis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myositis, Myasthenia Gravis
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2008to Dec 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Specific AAbs : anti-synthetases (anti-JO1, anti-PL7, or anti-PL12), or anti-SRP.
- 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:
- Extraocular muscle weakness quantified with MG muscle score (MMS), whose inter and inter observer reproducibility has been demonstrated [44].
- 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
Who cannot join
- Other muscular diseases, such as:
- Inclusion body myositis
- Macrophagic myofasciitis
- Inherited myopathies
- Secondary IM to one other connective tissue disorders
- Systemic scleroderma (ARA and/or "LEROY AND MEDSGER" criteria)
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- 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)
- Age < 18 years
- Pregnancy
- HIV seropositivity
- Evolutive infection (B, C hepatitis, tuberculosis)
- Lack of approved consent
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Médecine Interne 1 / Groupe Hospitalier Pitié-Salpêtrière
Paris, 75651 Cedex 13
About this study
Official title: FORCE: Rituximab (CD 20+-B Cell-depleting Monoclonal Antibody) for the Treatment of Refractory Inflammatory Myopathies With Specific Antibodies and Refractory Myasthenia Gravis
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.
Read the detailed description
Rituximab, a chimeric monoclonal antibody specific for human CD20, which targets B lymphocytes, has been first developed as biotherapy for the treatment of B lymphoma. In this context, hundred thousands patients received this drug, with a very good tolerance. Recently, interest has grown in the pivotal role of B cells for auto-immune humorally mediated diseases. Rituximab could then be a potential new biological treatment for such diseases, especially for patients refractory to conventional therapies. As a Muscular Diseases Centre, we have a large recruitment of patients with inflammatory myopathies (IM) and myasthenia gravis (MG). Although the physiopathogenesis of these two conditions differ, both can be associated with specific auto-antibodies (AAbs) and their therapeutic management is almost similar. The traditional treatment approach to IM and generalized 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. 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.
Inclusions criteria are IM (as defined by the 119th European Neuromuscular Centre workshop) or generalised MG (as defined by the Texas Clinical Classification System) associated with specific AAbs (anti-synthetases (JO1, PL7 or PL12), or anti-SRP for primary IM, and anti-AchR for MG) and refractory to conventional treatments 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.
The therapeutical schema is rituximab 1000 mg, 2 times (at day 0 and 15), followed by one single injection (1000 mg) 6 months latter and end of follow up at 1 year.
The efficacy is evaluated by an improvement of Kendall's muscular testing or MG muscular score at month 12. Secondary criteria include Kendall's muscular testing or MG muscular score at day 21 and month 7, quality of life auto-questionnaire (SF 36), evolution of CK levels and AAb titers.
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. If a success is observed in at least 6 patients, it will be possible to conclude that the response rate is above 25% (lower 90% confidence interval for observed response rate 50%).
- Conditions
- Myositis, Myasthenia Gravis
- Being tested
- Rituximab
- Keywords
- Myositis, Anti-synthetase, Anti-SRP, Myasthenia gravis, Rituximab
- Medical subject headings
- Myositis, Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Rituximab 1000 mg intravenous, 2 times, 2 weeks apart and 1000 mg 6 months after the last injection
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)
Measured: at month 12
Secondary outcomes (6)
- Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)
Measured: at day 21 and month 12
- Improvement of functional scale score (SF36)
Measured: at day 21 and month 12
- Decrease of CK levels
Measured: at day 21 and month 12
- Evolution of auto-antibody titers
Measured: 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
Measured: at day 21 and month 12
- Improvement in the treatment burden defined as the possibility to decrease the dose or stop some of the drugs used at entry
Measured: at day 21 and month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2008 (estimated)
- Study startJan 2008
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MyositisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Olivier BENVENISTE, PUPH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00774462
- Sponsor's protocol ID
- P051204
- Acronym
- FORCE
- Status last verified
- Dec 2007
- First submitted
- 16 Oct 2008
- Last updated
- 11 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26539981
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FORCE: Rituximab (CD 20+-B Cell-depleting Monoclonal Antibody) for the Treatment of Refractory Inflammatory Myopathies With Specific Antibodies and Refractory Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT00774462
- Acronym / sponsor ID
- FORCE / P051204
- Conditions
- Myositis, Myasthenia Gravis
- Keywords
- Myositis, Anti-synthetase, Anti-SRP, Myasthenia gravis, Rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Roche Pharma AG
- Study start
- Jan 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 17 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rituximab, a chimeric monoclonal antibody specific for human CD20, which targets B lymphocytes, has been first developed as biotherapy for the treatment of B lymphoma. In this context, hundred thousands patients received this drug, with a very good tolerance. Recently, interest has grown in the pivotal role of B cells for auto-immune humorally mediated diseases. Rituximab could then be a potential new biological treatment for such diseases, especially for patients refractory to conventional therapies. As a Muscular Diseases Centre, we have a large recruitment of patients with inflammatory myopathies (IM) and myasthenia gravis (MG). Although the physiopathogenesis of these two conditions differ, both can be associated with specific auto-antibodies (AAbs) and their therapeutic management is almost similar. The traditional treatment approach to IM and generalized 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. 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.
Inclusions criteria are IM (as defined by the 119th European Neuromuscular Centre workshop) or generalised MG (as defined by the Texas Clinical Classification System) associated with specific AAbs (anti-synthetases (JO1, PL7 or PL12), or anti-SRP for primary IM, and anti-AchR for MG) and refractory to conventional treatments 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.
The therapeutical schema is rituximab 1000 mg, 2 times (at day 0 and 15), followed by one single injection (1000 mg) 6 months latter and end of follow up at 1 year.
The efficacy is evaluated by an improvement of Kendall's muscular testing or MG muscular score at month 12. Secondary criteria include Kendall's muscular testing or MG muscular score at day 21 and month 7, quality of life auto-questionnaire (SF 36), evolution of CK levels and AAb titers.
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. If a success is observed in at least 6 patients, it will be possible to conclude that the response rate is above 25% (lower 90% confidence interval for observed response rate 50%).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Rituximab |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- For myositis III. Idiopathic myositis
- For myasthenia III. Generalised MG
- Extraocular muscle weakness quantified with MG muscle score (MMS), whose inter and inter observer reproducibility has been demonstrated [44].
- 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
Key exclusion criteria (21 listed)
- Other muscular diseases, such as:
- Secondary IM to one other connective tissue disorders
- Other myasthenic syndrome, such as:
- Cancer (or cancer-associated myositis)
- Age < 18 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabRituximab 1000 mg intravenous, 2 times, 2 weeks apart and 1000 mg 6 months after the last injection | Drug | 1 |
Primary outcome
Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)
Time frame: at month 12
6 secondary outcomes
- Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia)
Time frame: at day 21 and month 12
- Improvement of functional scale score (SF36)
Time frame: at day 21 and month 12
- Decrease of CK levels
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
- 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2012.
- Derived from this study: PubMed 26539981Allenbach 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier BENVENISTE, PUPH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Myositis and Myasthenia Gravis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia) (time frame: at month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00774462, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2012.