Systemic SclerosisPhase 2/3RECOVERNCT01748084
Rituximab in Systemic Sclerosis
A Phase 2/3 study testing Rituximab in people with Systemic Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteFrance
- Study dates
- 9 Apr 2013to 18 Apr 2016
- Phase
- Phase 2/3
- 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
- Systemic sclerosis fulfilling ACR or LeRoy's criteria
- Active polyarthritis defined by > 6/53 tender joints and > 4/53 swollen joints
- Ongoing first line therapy by prednisone (max 10 mg/d) and DMARDS (methotrexate, leflunomide, azathioprine or mycophenolate)
- Birth control if applicable
Who cannot join
- Overlap syndrome defined by clinical symptoms and positive specific auto-antibodies (anti-CCP, anti-SSA, anti-DNA DNA anti-Sm) (Rheumatoid factors and anti-RNP are not exclusion criteria)
- Past therapy with Rituximab.
- Severe and uncontrolled disease with renal, liver or haematological (neutropenia < 1500 / mm3) failures, pulmonary (FVC < 50%) or cardiac insufficiencies (LVEF < 50%)
- Not stable corticosteroid therapy or cyclophosphamide use in the last 6 months
- Infectious risk : viral infections by B or C hepatitis or HIV, hypogammaglobulinemia (< 6 G/L), opportunistic infection or infection requiring IV antibiotics in the last 3 months.
- Neoplastic solid tumor in the last 5 years
- Drug or alcool abuses
- Receiving patient or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis
The purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis
Read the detailed description
Systemic sclerosis (SSc) is a rare disease, characterized by microvascular and immunological changes promoting extra-cellular matrix synthesis and widespread fibrosis. No treatment has yet proven any ability to alter the disease fibrosing process. Specific auto-antibodies are commonly found in this disease, and B lymphocytes are detected in cutaneous and pulmonary infiltrates. Studies derived from murine models suggest a role for B lymphocyte blocking strategies.
This lead to observational trials of B-cell therapy using rituximab in SSc that provided encouraging results with no particular signal concerning tolerability. These trials included heterogeneous patients with variable disease stages and different involved organs, and were mostly unblinded, which preclude any definitive conclusion. However, they support the continuous development of this therapeutic approach.
Taking up the early phase of the diffuse form of the disease is complicated by its rarity and the heterogeneous progression of its visceral complications. This raises the question of selecting a homogeneous group of patients to evaluate. The most convincing results for the use of rituximab in autoimmune conditions have been found in rheumatoid arthritis. Joint involvement is common in SSc with 75% of patients complaining about joint stiffness and pain, and 30% presenting with synovitis, tenosynovitis, or flexion contractures. No specific treatment has already addressed this issue, and it is generally proposed to use small doses of oral corticosteroids in association with methotrexate, by analogy with rheumatoid arthritis. We propose to evaluate the efficacy and safety of rituximab in SSc patients having active arthritis despite first line treatment. Improving the articular involvement would improve the quality of life f SSc patients and effectiveness of rituximab on skin and lung fibrotic involvements will be assessed as secondary outcomes to estimate the overall effects of this drug on SSc.
- Conditions
- Systemic Sclerosis
- Being tested
- Rituximab, Placebo (NaCl)
- Keywords
- Systemic sclerosis, Arthritis, B-cell therapy, Anti-CD20 therapy, Quality of life, Scleroderma, Lung fibrosis, Randomised controled trial
- Medical subject headings
- Scleroderma, Systemic, Arthritis, Scleroderma, Diffuse, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone
Placebo (NaCl)Drug
Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone
| Study group | Role | What they receive |
|---|---|---|
| NaCl | Placebo comparator | NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone Receives: Drug: Placebo (NaCl) |
| Rituximab | Experimental | Rituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of tender and swollen joints
Measured out of 53 joints
Measured: at 6 months
Secondary outcomes (5)
Quality of life: SSc-HAQ
Validated scores
Measured: at 6 and 12 months
Scleroderma
modified Rodnan skin score
Measured: at 6 and 12 months
Lung fibrosis
Pulmonary functional tests
Measured: at 6 and 12 months
Quality of life: SF-36
Validated scores
Measured: at 6 and 12 months
Quality of life: Duruöz index
Validated scores
Measured: at 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2012 (estimated)
- Study start9 Apr 2013
- Primary completion18 Apr 2016
- Study completion18 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Yannick Allanore, MD, PhD, Principal investigator, Assistance Publique Hôpitaux de Paris, Université Paris Descartes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01748084
- Sponsor's protocol ID
- P110110
- Other IDs
- 2012-001636-56
- Acronym
- RECOVER
- Status last verified
- Oct 2025
- First submitted
- 10 Dec 2012
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bosello S, De Santis M, Lama G, Spano C, Angelucci C, Tolusso B, Sica G, Ferraccioli G. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12(2):R54. doi: 10.1186/ar2965. Epub 2010 Mar 25.
PubMed 20338043Simms RW, Lafyatis R. Rituximab: a potential therapeutic advance in scleroderma: what is the evidence? Rheumatology (Oxford). 2010 Feb;49(2):201-2. doi: 10.1093/rheumatology/kep421. Epub 2009 Dec 23. No abstract available.
PubMed 20032221Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Korfiatis P, Yiannopoulos G, Andonopoulos AP. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum. 2010 Oct;40(2):127-36. doi: 10.1016/j.semarthrit.2009.09.003. Epub 2009 Dec 11.
PubMed 20004954Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010 Feb;49(2):271-80. doi: 10.1093/rheumatology/kep093. Epub 2009 May 15.
PubMed 19447770Lafyatis R, Kissin E, York M, Farina G, Viger K, Fritzler MJ, Merkel PA, Simms RW. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):578-83. doi: 10.1002/art.24249.
PubMed 19180481
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis
- ClinicalTrials.gov ID
- NCT01748084
- Acronym / sponsor ID
- RECOVER / P110110
- Conditions
- Systemic Sclerosis
- Keywords
- Systemic sclerosis, Arthritis, B-cell therapy, Anti-CD20 therapy, Quality of life, Scleroderma, Lung fibrosis, Randomised controled trial
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 9 Apr 2013 (actual)
- Primary completion
- 18 Apr 2016 (actual)
- Study completion
- 18 Apr 2016 (actual)
- First posted
- 12 Dec 2012 (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 purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis
Detailed description
Systemic sclerosis (SSc) is a rare disease, characterized by microvascular and immunological changes promoting extra-cellular matrix synthesis and widespread fibrosis. No treatment has yet proven any ability to alter the disease fibrosing process. Specific auto-antibodies are commonly found in this disease, and B lymphocytes are detected in cutaneous and pulmonary infiltrates. Studies derived from murine models suggest a role for B lymphocyte blocking strategies.
This lead to observational trials of B-cell therapy using rituximab in SSc that provided encouraging results with no particular signal concerning tolerability. These trials included heterogeneous patients with variable disease stages and different involved organs, and were mostly unblinded, which preclude any definitive conclusion. However, they support the continuous development of this therapeutic approach.
Taking up the early phase of the diffuse form of the disease is complicated by its rarity and the heterogeneous progression of its visceral complications. This raises the question of selecting a homogeneous group of patients to evaluate. The most convincing results for the use of rituximab in autoimmune conditions have been found in rheumatoid arthritis. Joint involvement is common in SSc with 75% of patients complaining about joint stiffness and pain, and 30% presenting with synovitis, tenosynovitis, or flexion contractures. No specific treatment has already addressed this issue, and it is generally proposed to use small doses of oral corticosteroids in association with methotrexate, by analogy with rheumatoid arthritis. We propose to evaluate the efficacy and safety of rituximab in SSc patients having active arthritis despite first line treatment. Improving the articular involvement would improve the quality of life f SSc patients and effectiveness of rituximab on skin and lung fibrotic involvements will be assessed as secondary outcomes to estimate the overall effects of this drug on SSc.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NaCl | Placebo comparator | Drug: Placebo (NaCl)NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone |
| Rituximab | Experimental | Drug: RituximabRituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Systemic sclerosis fulfilling ACR or LeRoy's criteria
- Active polyarthritis defined by > 6/53 tender joints and > 4/53 swollen joints
- Ongoing first line therapy by prednisone (max 10 mg/d) and DMARDS (methotrexate, leflunomide, azathioprine or mycophenolate)
- Birth control if applicable
Key exclusion criteria (8 listed)
- Overlap syndrome defined by clinical symptoms and positive specific auto-antibodies (anti-CCP, anti-SSA, anti-DNA DNA anti-Sm) (Rheumatoid factors and anti-RNP are not exclusion criteria)
- Past therapy with Rituximab.
- Severe and uncontrolled disease with renal, liver or haematological (neutropenia < 1500 / mm3) failures, pulmonary (FVC < 50%) or cardiac insufficiencies (LVEF < 50%)
- Not stable corticosteroid therapy or cyclophosphamide use in the last 6 months
- Infectious risk : viral infections by B or C hepatitis or HIV, hypogammaglobulinemia (< 6 G/L), opportunistic infection or infection requiring IV antibiotics in the last 3 months.
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 |
|---|---|---|
| RituximabDays 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone | Drug | Rituximab |
| Placebo (NaCl)Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone | Drug | NaCl |
Primary outcome
Number of tender and swollen joints
Time frame: at 6 months
Measured out of 53 joints
5 secondary outcomes
Quality of life: SSc-HAQ
Time frame: at 6 and 12 months
Scleroderma
Time frame: at 6 and 12 months
Lung fibrosis
Time frame: at 6 and 12 months
Quality of life: SF-36
Time frame: at 6 and 12 months
Quality of life: Duruöz index
Time frame: at 6 and 12 months
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 20 Nov 2025.
- Background: PubMed 20338043Bosello S, De Santis M, Lama G, Spano C, Angelucci C, Tolusso B, Sica G, Ferraccioli G. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12(2):R54. doi: 10.1186/ar2965. Epub 2010 Mar 25.
- Background: PubMed 20032221Simms RW, Lafyatis R. Rituximab: a potential therapeutic advance in scleroderma: what is the evidence? Rheumatology (Oxford). 2010 Feb;49(2):201-2. doi: 10.1093/rheumatology/kep421. Epub 2009 Dec 23. No abstract available.
- Background: PubMed 20004954Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Korfiatis P, Yiannopoulos G, Andonopoulos AP. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum. 2010 Oct;40(2):127-36. doi: 10.1016/j.semarthrit.2009.09.003. Epub 2009 Dec 11.
- Background: PubMed 19447770Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010 Feb;49(2):271-80. doi: 10.1093/rheumatology/kep093. Epub 2009 May 15.
- Background: PubMed 19180481Lafyatis R, Kissin E, York M, Farina G, Viger K, Fritzler MJ, Merkel PA, Simms RW. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):578-83. doi: 10.1002/art.24249.
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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.
Yannick Allanore, MD, PhD principal investigator
Assistance Publique Hôpitaux de Paris, Université Paris Descartes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituximab in people with Systemic Sclerosis, 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 4 inclusion and 8 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 20 Nov 2025. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Number of tender and swollen joints (time frame: at 6 months). 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 NCT01748084, which also lists 5 linked publications.
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 20 Nov 2025.