Informations générales (source: ClinicalTrials.gov)
Multicenter Randomized Double-blind Study Comparing the 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) (TRIBECA)
Interventional
Phase 2
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
octobre 2021
octobre 2025
27 juin 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP Assistance publique - Hôpitaux de Paris | 18/04/2025 07:55:11 | Contacter | |||
| AP-HP - Hôpital Bicêtre | |||||
| AP-HP - Hôpital Europeen Georges Pompidou | |||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | |||||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | |||||
| AP-HP - Hôpital Necker-Enfants Malades | |||||
| AP-HP - Hôpital Saint Antoine | |||||
| AP-HP - Hôpital Tenon | |||||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| HOPITAL FOCH | David Saadoun, MD PhD | lundi 25 août 2025 | Contact (sur clinicalTrials) | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CH Blois - Blois - France | Bertrand Lioger, MD | Contact (sur clinicalTrials) | |||
| CH Nimes - Nimes - France | Olivier Moranne, MD | Contact (sur clinicalTrials) | |||
| CHU (Haut-Lévêque) - Bordeaux - France | Estibaliz Lazaro, MD | Contact (sur clinicalTrials) | |||
| CHU Caen - Caen - France | Achille Aouba, MD | Contact (sur clinicalTrials) | |||
| CHU La Conception - Marseille - France | Gilles Kaplanski, MD | Contact (sur clinicalTrials) | |||
| CHU Lille - Lille - France | Eric Hachulla, MD | Contact (sur clinicalTrials) | |||
| CHU Nantes - Nantes - France | Antoine Neel, MD | Contact (sur clinicalTrials) | |||
| CHU Starsbourg - Strasbourg - France | Jacques Eric Gottenberg, MD | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Toulouse - France | Stanislas Faguer, MD | Contact (sur clinicalTrials) | |||
| CHU Tours - Tours - France | Alexandra Audemard, MD | Contact (sur clinicalTrials) | |||
| CHU Valenciennes - Valenciennes - France | Thomas Quemeneur, MD | Contact (sur clinicalTrials) | |||
| Hopital Bicetre - Le Kremlin-Bicêtre - France | Xavier Mariette, MD | Contact (sur clinicalTrials) | |||
| Hopital Foch - Suresnes - France | Felix Ackermann, MD | Contact (sur clinicalTrials) | |||
| Hopital Henri Mondor - Créteil - France | Marc Michel, MD | Contact (sur clinicalTrials) | |||
| Hopital Saint Louis - Paris - France | Baptiste Hervier, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
The eligibility criteria will be checked at the inclusion/randomization visit. Patients
meeting the following criteria may be included in the study:
1. Age > 18 years
2. Written inform consent
3. 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
4. Affiliated to National French social security system
5. Having received Rituximab as induction therapy within 6 weeks (1 to 4 infusions,
dose at the discretion of the investigator)
6. Female subjects of childbearing potential must have a negative serum or urinary
pregnancy test at inclusion visit, and confirmed monthly while in study, out to at
least 92 days (5 half lives) post last dose.
7. 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:
1. 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
2. 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.
8. HIV negative serology ; negative HBs Ag test and HBc Ab test; HCV negative serology
or negative HCV RNA if positive HCV serology within 3 months before inclusion:
o In case of negative AgHBs and positive HBc Ab test, HBV DNA test must be negative;
AND Hepatitis B surveillance should be started (monthly HBsAg and HBV DNA testing
for the duration of the study treatment and at least every 12 weeks after treatment
is discontinued for the duration of study treatment. In addition, antiviral
prophylaxis should be started before the first administration of the study treatment
and continued until 12 months after completion of study treatment; HCV negative
serology or negative HCV RNA if positive HCV serology within 3 months before
inclusion
9. neutrophils (ANC) >1x109/L
Exclusion criteria :
Subjects will be not included from the study if they meet any of the following criteria:
1. Patient with a vasculitis unrelated to cryoglobulinemia
2. Patient with non active cryoglobulinemia vasculitis, at initiation of rituximab.
Patients with mixed inactive vasculitis following rituximab administration may be
included.
3. Excluded concomitant medications:
1. 365 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
2. 180 Days Prior to Investigational Medicinal Product (Belimumab or placebo)::
Intravenous cyclophosphamide
3. 30 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
4. Live vaccines within 30 days prior to baseline or concurrently with
Investigational Medicinal Product (Belimumab or placebo)
4. 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
5. 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
6. Have a Progressive multifocal leukoencephalopathy
7. Have a history of a primary immunodeficiency
9. Have a history of major organ transplant or hematopoietic stem cell/marrow
transplant or renal transplant
10. Infection history:
- Currently on any suppressive therapy for a chronic infection (such as tuberculosis,
pneumocystis, cytomegalovirus
- Infection requiring hospitalization and/or use of parenteral (IV or IM) antibiotics
(antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days
of the inclusion visit.
11. Have current drug or alcohol abuse or dependence, or a history of drug or
alcohol abuse or dependence within 365 days prior to the inclusion visit
12. Have a historically positive HIV test according to results obtained within 3
months prior to inclusion visit
13. Hepatitis status according to results obtained within 3 month prior to
inclusion visit :
- Positive test for hepatitis B RNA
- Positive test for Hepatitis C RNA
14. Have a history of a hypersensitivity or an anaphylactic reaction to parenteral
administration of Belimumab, corticosteroids or any excipients of the
treatments administered during the study
15. If Women of Child Bearing Potential (WCBP) are included please see special
instructions in Inclusion criteria
16. Pregnant or breast feeding women
17. Have any intercurrent significant medical or psychiatric illness that the
investigator considers would make the candidate unsuitable for the study
18. Patients under legal protection or unable to consent
19. Participation to another interventional study
The eligibility criteria will be checked at the inclusion/randomization visit. Patients
meeting the following criteria may be included in the study:
1. Age > 18 years
2. Written inform consent
3. 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
4. Affiliated to National French social security system
5. Having received Rituximab as induction therapy within 6 weeks (1 to 4 infusions,
dose at the discretion of the investigator)
6. Female subjects of childbearing potential must have a negative serum or urinary
pregnancy test at inclusion visit, and confirmed monthly while in study, out to at
least 92 days (5 half lives) post last dose.
7. 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:
1. 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
2. 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.
8. HIV negative serology ; negative HBs Ag test and HBc Ab test; HCV negative serology
or negative HCV RNA if positive HCV serology within 3 months before inclusion:
o In case of negative AgHBs and positive HBc Ab test, HBV DNA test must be negative;
AND Hepatitis B surveillance should be started (monthly HBsAg and HBV DNA testing
for the duration of the study treatment and at least every 12 weeks after treatment
is discontinued for the duration of study treatment. In addition, antiviral
prophylaxis should be started before the first administration of the study treatment
and continued until 12 months after completion of study treatment; HCV negative
serology or negative HCV RNA if positive HCV serology within 3 months before
inclusion
9. neutrophils (ANC) >1x109/L
Exclusion criteria :
Subjects will be not included from the study if they meet any of the following criteria:
1. Patient with a vasculitis unrelated to cryoglobulinemia
2. Patient with non active cryoglobulinemia vasculitis, at initiation of rituximab.
Patients with mixed inactive vasculitis following rituximab administration may be
included.
3. Excluded concomitant medications:
1. 365 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
2. 180 Days Prior to Investigational Medicinal Product (Belimumab or placebo)::
Intravenous cyclophosphamide
3. 30 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
4. Live vaccines within 30 days prior to baseline or concurrently with
Investigational Medicinal Product (Belimumab or placebo)
4. 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
5. 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
6. Have a Progressive multifocal leukoencephalopathy
7. Have a history of a primary immunodeficiency
9. Have a history of major organ transplant or hematopoietic stem cell/marrow
transplant or renal transplant
10. Infection history:
- Currently on any suppressive therapy for a chronic infection (such as tuberculosis,
pneumocystis, cytomegalovirus
- Infection requiring hospitalization and/or use of parenteral (IV or IM) antibiotics
(antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days
of the inclusion visit.
11. Have current drug or alcohol abuse or dependence, or a history of drug or
alcohol abuse or dependence within 365 days prior to the inclusion visit
12. Have a historically positive HIV test according to results obtained within 3
months prior to inclusion visit
13. Hepatitis status according to results obtained within 3 month prior to
inclusion visit :
- Positive test for hepatitis B RNA
- Positive test for Hepatitis C RNA
14. Have a history of a hypersensitivity or an anaphylactic reaction to parenteral
administration of Belimumab, corticosteroids or any excipients of the
treatments administered during the study
15. If Women of Child Bearing Potential (WCBP) are included please see special
instructions in Inclusion criteria
16. Pregnant or breast feeding women
17. Have any intercurrent significant medical or psychiatric illness that the
investigator considers would make the candidate unsuitable for the study
18. Patients under legal protection or unable to consent
19. Participation to another interventional study