CryoglobulinemiaPhase 2ESBAMNCT02556866
Rituximab Plus Corticosteroids in Non-infectious Active Mixed Cryoglobulinemia Vasculitis
A Phase 2 study testing rituximab and Prednisone in people with Cryoglobulinemia and Systemic Vasculitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Multicenter randomized double-blind study comparing the efficacy and safety of rituximab in combination with corticosteroids to corticosteroids plus placebo in the treatment of non-infectious active mixed cryoglobulinemia vasculitis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cryoglobulinemia, Systemic Vasculitis
- What is being tested?
- rituximab and Prednisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- 17 Jul 2015to 31 May 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must be at least 18 years of age or older, without any upper age limit
- Patient informed and agreed to participate, and gave informed consent,
- Patient with active cryoglobulinemia vasculitis define by positive cryoglobulinemia and a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement (no histological evidence needed if presence of purpura demonstrated),
- Patient with primary Sjögren's syndrome, systemic lupus erythematosus, or another auto-immune disease, or B-cell non-Hodgkin lymphoma (with cryoglobulinemia as the only therapeutic indication), or essential mixed cryoglobulinemia,
- Naive or relapsing patients, without modification (initiation or increase) of immunosuppressive therapy in the month prior the inclusion,
- For women of child bearing age: negative pregnancy test during the inclusion, and effective contraception during the period of 12 months after the latest rituximab infusion or placebo,
- Patients with severe vasculitis must be treated in the 15 days prior inclusion by 3 bolus of methylprednisolone (15 mg/kg/d) AND 3 to 7 plasma exchanges (exchange volume of 60 ml/kg/session).
Who cannot join
- Patient with a medium and small size vessels vasculitis unrelated to cryoglobulinemia (granulomatous with polyangiitis (Wegener's disease), microscopic polyangiitis, eosinophilic granulomatous with polyangiitis (Churg-Strauss syndrome), polyarteritis nodose, IgA vasculitis, hypersensitivity vasculitis, infectious vasculitis, hypocomplementemic urticarial vasculitis),
- Patient with a large size vessels vasculitis,
- Patient with non active cryoglobulinemia vasculitis,
- Patient with immunosuppressive therapy introduced or increased in the month prior to the inclusion,
- Patients receiving corticosteroid therapy > 0.5 mg/kg/d for more than one month before the inclusion or > 1 mg/kg/d for more than two weeks before the inclusion,
- Patient who had received rituximab therapy within the 12 months before the inclusion,
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- Pregnancy in progress or needed , breast feeding,
- HIV-positive status,
- Patient with active hepatitis B or C infection,
- HBs Ag-positive and/or HBV DNA detectable in the blood*,
- Patients with known hypersensitivity reaction to the active substance or any of the excipients, or to murine proteins,
- Contraindication to rituximab,
- Active infections at screening,
- Patient in guardianship,
- Patient already included in a biomedical research protocol,
- No social security scheme (Beneficiaries or eligible),
- History of cancer during the last 3 years before inclusion, including solid tumors, hematological malignancies (except lymphoproliferative disorder associated with the mixed cryoglobulinemia vasculitis), and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been treated or excized and cured)"
- If the hepatitis B core antibody (anti-HBc) is positive, the benefit/risk will be evaluated by an hepatologist before inclusion, and patient, if enrolled, will be monitored until the end of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter Randomized Double-blind Study Comparing the Efficacy and Safety of Rituximab in Combination With Corticosteroids to Corticosteroids Plus Placebo in the Treatment of Non-infectious Active Mixed Cryoglobulinemia Vasculitis
Multicenter randomized double-blind study comparing the efficacy and safety of rituximab in combination with corticosteroids to corticosteroids plus placebo in the treatment of non-infectious active mixed cryoglobulinemia vasculitis.
Read the detailed description
Cryoglobulinemia are responsible for systemic vasculitis, and the most frequently targeted organs are the skin, joints, kidneys and peripheral nervous system. Cryoglobulinemia vasculitis are associated with significant morbidity and mortality, and require therapeutic intervention. Management of non-infectious mixed cryoglobulinemia vasculitis is based on corticosteroids, plasma exchange, and/or immunosuppressants. These treatments are associated with frequent side effects. To date, no study has evaluated the efficacy and safety of these different therapeutic options, explaining the lack of recommendations.
Rituximab, a monoclonal antibody directed against CD20, has emerged as a novel therapeutic option in B-cell related disorders. Data from the French AutoImmunity and Rituximab (AIR) registry recently reported the positive effect of rituximab in non-infectious mixed cryoglobulinemia vasculitis. More recently, the multidisciplinary national French CryoVas survey also suggested a significant superiority of the combination corticosteroid plus rituximab compared to the corticosteroids alone in terms of complete clinical and immunological responses and corticosteroid sparing. However, no randomized controlled data addressing this issue has been published to date.
- Conditions
- Cryoglobulinemia, Systemic Vasculitis
- Being tested
- rituximab, Prednisone, Placebo
- Medical subject headings
- Cryoglobulinemia, Systemic Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
Prednisone treatment plus rituximab administered by slow intravenous infusion at 375 mg/m2 at D1, D8, D15 and D22.
PrednisoneDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| rituximab | Experimental | Prednisone treatment plus rituximab administered by slow intravenous infusion at 375 mg/m2 at D1, D8, D15 and D22. Receives: Drug: rituximab; Drug: Prednisone |
| placebo | Placebo comparator | Prednisone treatment plus placebo administered by slow intravenous infusion at day 1 (D1), D8, D15 and D22. Receives: Drug: Prednisone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete clinical response of vasculitis symptoms (yes-no, i.e. success-failure) with corticosteroid withdrawal (prednisone at 0 mg/day) at week (W) 24, with at least one clinical response at W4
The complete clinical response is defined by the remission of all affected organs involved at baseline and the absence of clinical relapse.
Measured: Week 24
Secondary outcomes (1)
Partial clinical response
Partial clinical response defined by an improvement of at least half of organ impairments present at baseline
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2015 (estimated)
- Study start17 Jul 2015
- Primary completion31 May 2018
- Study completion31 May 2018
Why it stopped: lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CryoglobulinemiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrice CACOUB, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02556866
- Sponsor's protocol ID
- P120122
- Other IDs
- 2013-000844-24
- Acronym
- ESBAM
- Status last verified
- Mar 2019
- First submitted
- 20 Jul 2015
- Last updated
- 18 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Randomized Double-blind Study Comparing the Efficacy and Safety of Rituximab in Combination With Corticosteroids to Corticosteroids Plus Placebo in the Treatment of Non-infectious Active Mixed Cryoglobulinemia Vasculitis
- ClinicalTrials.gov ID
- NCT02556866
- Acronym / sponsor ID
- ESBAM / P120122
- Conditions
- Cryoglobulinemia, Systemic Vasculitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of recruitment
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 17 Jul 2015 (actual)
- Primary completion
- 31 May 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 22 Sep 2015 (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.
Multicenter randomized double-blind study comparing the efficacy and safety of rituximab in combination with corticosteroids to corticosteroids plus placebo in the treatment of non-infectious active mixed cryoglobulinemia vasculitis.
Detailed description
Cryoglobulinemia are responsible for systemic vasculitis, and the most frequently targeted organs are the skin, joints, kidneys and peripheral nervous system. Cryoglobulinemia vasculitis are associated with significant morbidity and mortality, and require therapeutic intervention. Management of non-infectious mixed cryoglobulinemia vasculitis is based on corticosteroids, plasma exchange, and/or immunosuppressants. These treatments are associated with frequent side effects. To date, no study has evaluated the efficacy and safety of these different therapeutic options, explaining the lack of recommendations.
Rituximab, a monoclonal antibody directed against CD20, has emerged as a novel therapeutic option in B-cell related disorders. Data from the French AutoImmunity and Rituximab (AIR) registry recently reported the positive effect of rituximab in non-infectious mixed cryoglobulinemia vasculitis. More recently, the multidisciplinary national French CryoVas survey also suggested a significant superiority of the combination corticosteroid plus rituximab compared to the corticosteroids alone in terms of complete clinical and immunological responses and corticosteroid sparing. However, no randomized controlled data addressing this issue has been published to date.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rituximab | Experimental | Drug: rituximab, Drug: PrednisonePrednisone treatment plus rituximab administered by slow intravenous infusion at 375 mg/m2 at D1, D8, D15 and D22. |
| placebo | Placebo comparator | Drug: Prednisone, Drug: PlaceboPrednisone treatment plus placebo administered by slow intravenous infusion at day 1 (D1), D8, D15 and D22. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The patient must be at least 18 years of age or older, without any upper age limit
- Patient informed and agreed to participate, and gave informed consent,
- Patient with active cryoglobulinemia vasculitis define by positive cryoglobulinemia and a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement (no histological evidence needed if presence of purpura demonstrated),
- Patient with primary Sjögren's syndrome, systemic lupus erythematosus, or another auto-immune disease, or B-cell non-Hodgkin lymphoma (with cryoglobulinemia as the only therapeutic indication), or essential mixed cryoglobulinemia,
- Naive or relapsing patients, without modification (initiation or increase) of immunosuppressive therapy in the month prior the inclusion,
Key exclusion criteria (18 listed)
- Patient with a medium and small size vessels vasculitis unrelated to cryoglobulinemia (granulomatous with polyangiitis (Wegener's disease), microscopic polyangiitis, eosinophilic granulomatous with polyangiitis (Churg-Strauss syndrome), polyarteritis nodose, IgA vasculitis, hypersensitivity vasculitis, infectious vasculitis, hypocomplementemic urticarial vasculitis),
- Patient with a large size vessels vasculitis,
- Patient with non active cryoglobulinemia vasculitis,
- Patient with immunosuppressive therapy introduced or increased in the month prior to the inclusion,
- Patients receiving corticosteroid therapy > 0.5 mg/kg/d for more than one month before the inclusion or > 1 mg/kg/d for more than two weeks before the inclusion,
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 |
|---|---|---|
| rituximabPrednisone treatment plus rituximab administered by slow intravenous infusion at 375 mg/m2 at D1, D8, D15 and D22. | Drug | rituximab |
| Prednisone | Drug | placebo, rituximab |
| Placebo | Drug | placebo |
Primary outcome
Complete clinical response of vasculitis symptoms (yes-no, i.e. success-failure) with corticosteroid withdrawal (prednisone at 0 mg/day) at week (W) 24, with at least one clinical response at W4
Time frame: Week 24
The complete clinical response is defined by the remission of all affected organs involved at baseline and the absence of clinical relapse.
1 secondary outcome
Partial clinical response
Time frame: Week 24
Results and safety
The study was stopped early (reason given: lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2019.
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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.
Patrice CACOUB, MD, PhD 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 and Prednisone in people with Cryoglobulinemia and Systemic Vasculitis, 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 7 inclusion and 18 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: stopped early, as of the sponsor's last update on 18 Mar 2019. 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 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 was stopped early (reason given: lack of recruitment). Results are not available in the source record.
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?
Complete clinical response of vasculitis symptoms (yes-no, i.e. success-failure) with corticosteroid withdrawal (prednisone at 0 mg/day) at week (W) 24, with at least one clinical response at W4 (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2019; AzTrials last refreshed its copy on 7 Nov 2026.