Actively Recruiting
Efficacy and Safety of Subcutaneous Belimumab or Placebo in Addition of Rituximab in Persistent or Chronic Immune Thrombocytopenia
Led by Assistance Publique - Hôpitaux de Paris · Updated on 2023-09-11
132
Participants Needed
1
Research Sites
260 weeks
Total Duration
On this page
Sponsors
A
Assistance Publique - Hôpitaux de Paris
Lead Sponsor
G
GlaxoSmithKline
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
CONDITIONS
Official Title
Efficacy and Safety of Subcutaneous Belimumab or Placebo in Addition of Rituximab in Persistent or Chronic Immune Thrombocytopenia
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Diagnosis of primary immune thrombocytopenia (ITP) according to standard criteria
- Previous response to corticosteroids and/or intravenous immunoglobulin followed by relapse
- Platelet count 30 x 10^9/L or less in the past month, or less than 50 x 10^9/L with bleeding or other reasons
- ITP duration between 2 months and 5 years from diagnosis
- Normal bone marrow smear for patients over 60 years old
- Negative pregnancy test and use of effective contraception for women of childbearing potential
- Complete COVID-19 vaccination as recommended by health authorities
- Gammaglobulin level of at least 7 g/L
- Signed informed consent
- Affiliated with or beneficiary of a social security or similar system
You will not qualify if you...
- Previous splenectomy
- Prior treatment with rituximab or any B-cell targeted therapy
- Common variable immunodeficiency
- Previous treatment with cyclophosphamide or ciclosporin
- Participation in another clinical trial within 3 months
- History of anaphylactic shock to biologic therapy
- Severe or ongoing infection requiring treatment or hospitalization in past 60 days
- Use of parenteral antibiotics within 60 days or suppressive therapy for chronic infections
- Serious suicide risk or recent suicidal behavior or ideation
- Psychiatric illness impairing judgment
- Neutrophil count below 1,000/mm3 at inclusion
- Positive HIV, hepatitis B or C infection tests
- Impaired kidney function with serum creatinine over 2 mg/dl
- Liver enzyme levels more than 5 times normal or bilirubin over 3 times normal
- Severe heart disease (NYHA class III or IV)
- History of cancer in last 5 years except cutaneous carcinoma
- History of progressive multifocal leukoencephalopathy
- History of major organ or stem cell transplant
- Current or recent alcohol or drug abuse
- Pregnant or breastfeeding women
- Live attenuated vaccines within 30 days before study
- Significant illness or lab abnormalities that interfere with study or safety
- Body mass index over 40
- Confirmed COVID-19 infection by PCR
- Vulnerable persons under legal protection or unable to consent
AI-Screening
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Trial Site Locations
Total: 1 location
1
Henri Mondor Hospital
Créteil, France, 9400
Actively Recruiting
Research Team
M
Matthieu MAHEVAS, Professor of medicine
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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