Efficacy and Safety of Subcutaneous Belimumab or Placebo in Addition of Rituximab in Persistent or Chronic Immune Thrombocytopenia

Sponsor
Assistance Publique - Hôpitaux de Paris
Study ID
NCT05338190
Phase
PHASE3
Status
Recruiting
Apply to this trial

Conditions

  • Primary Immune Thrombocytopenia (ITP)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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

Key Dates

Start date
Nov 14, 2022
Status verified
Sep 2023
Primary completion
Nov 14, 2026
Completion
Nov 14, 2027

Study Design

Enrollment
132 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: ARM A
    Belimumab 200 mg subcutaneous weekly (i.e., every 7 days ±1 day) starting from day 0 through week 24 with 1 g intravenous of Rituximab 7 days and 21 days after the randomization.
  • Placebo Comparator: ARM B
    Placebo subcutaneous weekly (i.e., every 7 days ±1 day starting from day 0) starting from day 0 through week 24 with 1 g intravenous of Rituximab 7 days and 21 days after the randomization.

Primary Outcome Measure

The overall response rate (CR + R) in both arms at W52 [ Time Frame: Week 52 ]

Central Contacts

Related Studies