Phase 3 Open-label with BIVV009 in Subjects with CAgD

  • Research type

    Research Study

  • Full title

    A PIVOTAL, OPEN-LABEL, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY OF BIVV009 IN PATIENTS WITH PRIMARY COLD AGGLUTININ DISEASE WHO HAVE A RECENT HISTORY OF BLOOD TRANSFUSION

  • IRAS ID

    235022

  • Contact name

    Shirley D'Sa

  • Contact email

    s.d'sa@nhs.net

  • Sponsor organisation

    Bioverativ USA Inc.

  • Eudract number

    2017-003538-10

  • Clinicaltrials.gov Identifier

    HAEM 36389 , NIHR CRN-CTMS ID

  • Duration of Study in the UK

    2 years, 6 months, 0 days

  • Research summary

    Research Summary

    Cold agglutinin disease (CAgD) is an autoimmune disease where the body recognises its own red blood cells as foreign and therefore produces antibodies against them. This interaction between the antibodies and red blood cells activates another compound of the immune system called Complement, which in normal conditions helps the body to fight infections and diseases. The activation of the Complement leads to the breakdown of the red blood cells and subsequently to anaemia. Generally, the exposure to cold temperatures triggers the clinical manifestations.

    Currently, there is no authorised medicinal product available to treat CAgD. The disease management is mainly supportive and involves blood transfusions and simply avoiding cold temperatures. Therefore, there is a significant need for novel therapy approaches to tackle the disease.

    The investigational drug BIVV009 has been developed to prevent the activation of the Complement. BIVV009 is a humanised monoclonal antibody, which has been made in the laboratory. BIVV009 can bind to the Complement, block its activity and prevent the breakdown of the red blood cells.

    The purpose of this study is to evaluate the safety and potential side effect triggered by BIVV009. The study will also assess the effectiveness of the study drug in improving the condition of patients affected by CAgD.

    The study consists of two phase treatments:
    - Part A where all the eligible patients will receive BIVV009 every two weeks by intravenous infusion during a 25 weeks period
    - Part B as a long-term safety and response durability phase, where patients at the end of the part A period will be able to continue with BIVV009 until the last patient enrolled in this period completes one year.

    The study could last for a minimum of 1.5 years including 6 weeks of screening for subject eligibility.

    In total, there will be about 20 subjects participating in this study around the world including approximately 2 from the UK.

    Summary of Results

    Sutimlimab (study drug) has been developed for the treatment of hemolysis in adult patients with cold agglutinin disease (CAD). This study was conducted in two parts to evaluated the safety, tolerability and durability of effect in patients with CAD.
    22 Patients completed Part A and rolled over into Part B, the longterm extension study.
    The data form Part B suggest that, with long-term treatment with sutimlimab, haemoglobin levels remain increased over baseline and haemolysis continues to be inhibited. Fatigue also remains improved.
    In contrast, once sutimlimab was no longer administered (as per protocol design), there was evidence of a return of haemolysis activity.
    A comprehensive medical review of the complete Adverse Event (AE) listing data was performed to identify AEs that might represent possible hypersensitivity or allergic reactions to sutimlimab.
    No Treatment Emerging AEs suggestive of anaphylaxis were reported.
    Two thromboembolic events were reported in 2 patients, but both were assessed by the Investigator as unrelated to the study drug (sutimlimab).
    There were no clinically meaningful trends in vital sign assessments.
    No patient had a shift from a normal to abnormal electrocardiogram (ECG that was reported as an AE).
    Overall, sutimlimab was generally well tolerated, with a safety profile consistent with previous studies.
    In conclusion, the results of Part B of the study, which had a duration of treatment ranging from 28 to 151 weeks, demonstrate consistent and sustained control of haemolysis, improvement in anaemia and quality of life and no new safety concerns, which supports the continued favourable risk-benefit profile of sutimlimab for the treatment of haemolysis in patients with CAD.

  • REC name

    London - Harrow Research Ethics Committee

  • REC reference

    17/LO/1920

  • Date of REC Opinion

    26 Feb 2018

  • REC opinion

    Further Information Favourable Opinion