Informations générales (source: ClinicalTrials.gov)
A Phase 3 Randomized and Double-blind Controlled Trial Comparing the Efficacy and Safety of Subcutaneous Belimumab or Placebo in Addition to Rituximab in Adult Patients With Persistent or Chronic Immune Thrombocytopenia (ITP) (RITUX-PLUS 2)
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
novembre 2022
novembre 2027
29 juin 2024
Primary immune thrombocytopenia (ITP) is an autoimmune disease mainly mediated by
autoreactive B cells and the presence of pathogenic anti-platelet auto-antibodies that
enhance platelet destruction and impair platelet production. There are approximately
4,000 newly diagnosed ITP cases each year in France. For patients with a platelet count
of less than 30x109/L and/or bleeding symptoms, corticosteroids alone or in combination
with intravenous immunoglobulin (IVIg) is the standard first-line treatment. However,
approximately two-thirds of adult patients responding to this first-line treatment
relapse within days or weeks after corticosteroids withdrawal and overall, the course of
the disease is chronic in about 70% of the cases. The anti-CD20 monoclonal antibody
rituximab is commonly used off-label as a second-line therapy in many European countries
including France for adults with persistent (i.e., disease duration of more than 3
months) or chronic (disease duration of more than 12 months) ITP. Rituximab leads to an
overall response rate of only 40 % at 1 year but 29.5% of lasting (5 years and more)
response The investigators have shown that the absence of response to rituximab in ITP
could be explained by the settlement and expansion of long-lived autoreactive plasma
cells in the spleen made possible by the high amount of BAFF. Belimumab is a fully
humanized anti-BAFF/Blys monoclonal Ab licensed for SLE. Based on the preliminary results
of a phase 2 open prospective pilot study performed in our center combining rituximab
with i.v belimumab seems highly promising We hypothesized that combining subcutaneous
belimumab weekly over a 24 weeks period (Arm A) with rituximab is superior to rituximab
and subcutaneous placebo weekly over 24 weeks period (Arm B) to achieve an overall
response at W52.
The study design will be a prospective randomized, double-blind, multicenter
(international), superiority phase III clinical study
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Antoine Béclère | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Bicêtre | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Bichat | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Cochin | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Europeen Georges Pompidou | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| AP-HP - Hôpital Saint Antoine | MAHEVAS Matthieu | 18/04/2025 07:55:36 | Contacter | ||
| HOPITAL FOCH | MATHILDE ROUMIER | 05/05/2025 07:12:12 | Contacter | ||
Critères
Tous
Inclusion Criteria:
1. Age ≥ 18 years
2. Primary ITP defined according to the standard definition criteria (Rodeghiero, Blood
2008)
3. Previous response to corticosteroids and/or IgIV defined by a rise of platelet
levels > 30 x 109/L with at least a twofold increase from baseline levels followed
by a relapse.
4. Platelet count ≤ 30 x 109/L within the previous month or <50 x 109/L if presence of
haemorrhagic events or other reason left up to investigator discretion.
5. ITP duration of more than 2 months but less than 5 years from diagnosis.
6. Normal bone marrow smear for patients above 60 years of age
7. Negative pregnancy test results and effective contraception for women of
childbearing age Female subjects of childbearing potential must not become pregnant
and so must be sexually inactive by abstinence or use contraceptive methods with a
failure rate of < 1%.
Therefore, these women must have a negative serum pregnancy test at screening, and
confirmed monthly while in study (with serum or Urine test), out to at least 12
months (taking account of the longest half-life which is that of 29.7 days and
according to smPC) post last dose and agree to 1 of the following:
- Complete abstinence from intercourse from 2 weeks prior to administration of
the 1st dose of study agent until 16 weeks 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 16 weeks after the last dose of study agent
- Oral contraceptive, either combined or progestogen alone
- Injectable progestogen
- Implants of levonorgestrel or etonogestrel
- Estrogenic vaginal ring
- Percutaneous contraceptive patches
- Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure
rate as stated in the product label
- 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. Complete Vaccinal scheme against SARS-CoV2 according to the recommendations of the
health authorities
9. Gammaglobulin level ≥ 7 g/L
10. Informed consent
11. Affiliated to, or beneficiary of, a social security regime or similar
1. Age ≥ 18 years
2. Primary ITP defined according to the standard definition criteria (Rodeghiero, Blood
2008)
3. Previous response to corticosteroids and/or IgIV defined by a rise of platelet
levels > 30 x 109/L with at least a twofold increase from baseline levels followed
by a relapse.
4. Platelet count ≤ 30 x 109/L within the previous month or <50 x 109/L if presence of
haemorrhagic events or other reason left up to investigator discretion.
5. ITP duration of more than 2 months but less than 5 years from diagnosis.
6. Normal bone marrow smear for patients above 60 years of age
7. Negative pregnancy test results and effective contraception for women of
childbearing age Female subjects of childbearing potential must not become pregnant
and so must be sexually inactive by abstinence or use contraceptive methods with a
failure rate of < 1%.
Therefore, these women must have a negative serum pregnancy test at screening, and
confirmed monthly while in study (with serum or Urine test), out to at least 12
months (taking account of the longest half-life which is that of 29.7 days and
according to smPC) post last dose and agree to 1 of the following:
- Complete abstinence from intercourse from 2 weeks prior to administration of
the 1st dose of study agent until 16 weeks 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 16 weeks after the last dose of study agent
- Oral contraceptive, either combined or progestogen alone
- Injectable progestogen
- Implants of levonorgestrel or etonogestrel
- Estrogenic vaginal ring
- Percutaneous contraceptive patches
- Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure
rate as stated in the product label
- 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. Complete Vaccinal scheme against SARS-CoV2 according to the recommendations of the
health authorities
9. Gammaglobulin level ≥ 7 g/L
10. Informed consent
11. Affiliated to, or beneficiary of, a social security regime or similar
1. Splenectomy
2. Previous treatment with rituximab or any B-cell targeted therapy
3. Common variable immunodeficiency
4. Previous treatment with cyclophosphamide or ciclosporin
5. Inclusion in another clinical trial less than 3 months before inclusion
6. Previous anaphylactic shock to previous biologic therapy
7. Chronic or ongoing severe infection requiring treatment or hospitalization in the 60
days preceding inclusion.
8. Use of parenteral antibiotics within 60 days, current use of suppressive therapy for
chronic infection such as tuberculosis, pneumocystis, cytomegalovirus, HSZ, herpes
zoster, and atypical mycobacteria
9. Evidence of serious suicide risk including any history of suicidal behavior 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.
10. Psychiatric Illness impairing judgement.
11. Neutrophils count < 1,000/mm3 at inclusion
12. Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B
virus surface antigen or core antibody (HbsAg or HBcAb)
13. Impaired renal function as indicated by a serum creatinine level > 2 mg/dl
14. Liver function: AST (SGOT) and ALT (SGPT) ≥5xULN Total bilirubin ≥3 x ULN
15. New York Heart Classification III or IV heart disease
16. Previous history of malignancy in the last 5 years other than cutaneous carcinoma
17. Previous history of Progressive multifocal leukoencephalopathy
18. Previous history of major organ transplant or hematopoietic stem cell/marrow
transplant or renal transplant.
19. Alcohol or drug abuse or dependence, either current or within 1year
20. Pregnant or breast-feeding woman
21. Live, attenuated vaccinations must be administered at least 30 days before inclusion
in study
22. History of significant medical illness or clinically significant laboratory
abnormality (or planned surgical procedure) which in the opinion of the investigator
would interfere with the study procedures and / or assessments or compromise subject
safety
23. Body mass index > 40
24. PCR-confirmed SARS-CoV-2 infection
25. Vulnerable persons, under the protection of justice,
26. Persons deprived of their liberty by judicial or administrative decision,
27. Persons admitted to a health or social establishment for purposes other than
research,
28. Persons under legal protection (guardianship, curatorship),
29. Persons unable to express their consent