Efficacy and Safety of Belimumab in the Treatment of Non-infectious Active Cryoglobulinemia Vasculitis Compared to Placebo. TRIBECA STUDY (Treatment nd BElimumab in Cryoglobulinemia Associated Vasculitis)

NCT04629144 | Recruiting Phase 2 DMC

• 1 other identifier: APHP180351
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 20

Brief Summary

Cryoglobulinemia vasculitis (CV) is a systemic immune-mediated small vessel vasculitis. Rituximab proved effective on main vasculitis signs, with a complete clinical response of 65%. However, CV relapse is noted in up to 40% of patients. Following rituximab, serum Blys concentration significantly increased and may favor relapses. Tribeca is a multicentre randomized controled study comparing safety and efficacy of belimumab to placebo in non infectious cryoglobulinemia vasculitis.

Conditions

Vasculitis; Cryoglobulinemia

Keywords

Belimumab; Vasculitis; Cryoglobulinemia; Non-infectious

Outcome Measures

Primary Outcomes (1)

• Complete clinical response rate at week 25 with corticosteroid withdrawal at week 12

  Complete clinical response is defined by remission of all affected organs involved at baseline and the absence of clinical relapse. * Skin and articular remissions * Renal remission * Neurological remission * Digestive remission * Cardiac remission * Central nervous system remission * Pulmonary remission

  Week 25

Secondary Outcomes (28)

• Safety W25

  Week 25

• Safety W48

  Week 48

• Response W13

  Week 13

• Response W25

  Week 25

• Response W48

  Week 48

Other Outcomes (5)

• Immunomonitoring W13

  Week 13

• Immunomonitoring W25

  Week 25

• Immunomonitoring W48

  Week 48

Study Arms (2)

Belimumab

EXPERIMENTAL

Belimumab administered subcutaneously 200mg weekly from week 1 to week 24.

Drug: Belimumab

Placebo

PLACEBO COMPARATOR

Placebo of Belimumab administered subcutaneously weekly from week 1 to week 24.

Drug: Placebo

Interventions

Belimumab DRUG

Belimumab administered subcutaneously 200mg weekly from week 1 to week 24. Both arms will have the same corticosteroid tapering scheme, with an initial dose of 30 mg/day. The following schedule of reduction of prednisone will apply to both groups as long as the disease is inactive: * 30 mg/day week (W)0-W2, * 20 mg/day W2-W4 * 15 mg/day W4-W6, * 10 mg/day W6-W8, * 5 mg/day W8-W10 Between W10-W12 the strategy for stopping glucocorticoids is left to the investigator's discretion. Stopping glucocorticoid therapy at W12. At each step, the prednisone dose will be reduced only in the absence of signs of vasculitis activity.

Belimumab

Placebo DRUG

Both arms will have the same corticosteroid tapering scheme, with an initial dose of 30 mg/day. The following schedule of reduction of prednisone will apply to both groups as long as the disease is inactive: * 30 mg/day week (W)0-W2, * 20 mg/day W2-W4 * 15 mg/day W4-W6, * 10 mg/day W6-W8, * 5 mg/day W8-W10 Between W10-W12 the strategy for stopping glucocorticoids is left to the investigator's discretion. Stopping glucocorticoid therapy at W12. At each step, the prednisone dose will be reduced only in the absence of signs of vasculitis activity.

Placebo

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Written inform consent
• Active mixed cryoglobulinemia vasculitis, at initiation of rituximab, define by a. a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement , b. history of positive cryoglobulinemia and/or positive Rheumatoid factor associated with low C4 complement level , and/or a monoclonal component (IgM Kappa) and/or a histologal proof of vasculitis in the affected organs
• Affiliated to National French social security system
• Having received Rituximab as induction therapy within 6 weeks (1 to 4 infusions, dose at the discretion of the investigator)
• For subjects with reproductive potential (male or female), a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study from 2 weeks prior to administration of the 1st dose of study agent until 92 days after the last dose of study agent. Therefore the subjects agree to 1 of the following:
• Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 92 days after the last dose of study agent (Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception) OR
• Consistent and correct use of 1 of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 92 days after the last dose of study agent o Oral contraceptive, either combined or progestogen alone o Injectable progestogen o Implants of levonorgestrel or etonogestrel o Estrogenic vaginal ring o Percutaneous contraceptive patches o Intrauterine device (IUD) or intrauterine system (IUS) with \<1% failure rate as stated in the product label
• o Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records
• Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception.
• neutrophils (ANC) \>1x109/L

You may not qualify if:

• Subjects will be not included from the study if they meet any of the following criteria:
• Patient with a vasculitis unrelated to cryoglobulinemia
• Patient with non active cryoglobulinemia vasculitis, at initiation of rituximab. Patients with mixed inactive vasculitis following rituximab administration may be included.
• Excluded concomitant medications:
• days Prior to Investigational Medicinal Product (Belimumab or placebo):: Any biologic investigational agent (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131) Investigational agent applies to any drug not approved for sale in the country in which it is being used
• Days Prior to Investigational Medicinal Product (Belimumab or placebo):: Intravenous cyclophosphamide
• Days Prior to Investigational Medicinal Product (Belimumab or placebo): (or 5 half lives, whichever is greater) Any non-biologic investigational agent Investigational agent applies to any drug not approved for sale in the country in which it is being use
• Live vaccines within 30 days prior to baseline or concurrently with Investigational Medicinal Product (Belimumab or placebo)
• Have a history of malignant neoplasm within the last 5 years, other than carcinoma in situ of the cervix or excised basal cell, squamous cell carcinoma of the skin and low grade hemopathy with no indication for a specific treatment
• Have evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk
• Have a Progressive multifocal leukoencephalopathy
• Have a history of a primary immunodeficiency
• \. Have a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant
• \. Infection history:
• Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (20)

CH Blois

Blois, France

RECRUITING

CHU (Haut-Lévêque)

Bordeaux, France

RECRUITING

CHU Caen

Caen, France

RECRUITING

Hopital Henri Mondor

Créteil, France

NOT YET RECRUITING

Hopital Bicetre

Le Kremlin-Bicêtre, France

RECRUITING

CHU Lille

Lille, France

RECRUITING

CHU La Conception

Marseille, France

RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CH Nimes

Nîmes, France

RECRUITING

Hopital de La Pitié Salpetriere AP-HP

Paris, France

RECRUITING

Hopital Européen Georges Pompidou

Paris, France

RECRUITING

Hopital Necker

Paris, France

RECRUITING

Hopital Saint Antoine

Paris, France

RECRUITING

Hopital Saint Louis

Paris, France

RECRUITING

Hopital Tenon

Paris, France

RECRUITING

CHU Starsbourg

Strasbourg, France

RECRUITING

Hopital Foch

Suresnes, France

RECRUITING

CHU Toulouse

Toulouse, France

RECRUITING

CHU Tours

Tours, France

RECRUITING

CHU Valenciennes

Valenciennes, France

RECRUITING

MeSH Terms

Conditions

Vasculitis; Cryoglobulinemia

Interventions

belimumab

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

David Saadoun, MD PhD

CONTACT

142499742; david.saadoun@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 16, 2020
• Study Start: October 20, 2021
• Primary Completion: April 20, 2025
• Study Completion: October 20, 2025
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

FR (20)