Phase 3 with BIVV009/Placebo in Subjects with CAgD

• Research type

  Research Study

• Full title

  A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF BIVV009 IN PATIENTS WITH PRIMARY COLD AGGLUTININ DISEASE WITHOUT A RECENT HISTORY OF BLOOD TRANSFUSION

• IRAS ID

  236323

• Contact name

  Shirley D'Sa

• Contact email

  s.d'sa@nhs.net

• Sponsor organisation

  Bioverativ USA Inc.

• Eudract number

  2017-003539-12

• Clinicaltrials.gov Identifier

  HAEM 36512 , NIHR CRN- CPMS ID

• Duration of Study in the UK

  3 years, 0 months, 6 days

• Research summary

  Summary of Research

  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. Complement activation leads to the breakdown of the red blood cells and subsequently to anaemia. Generally, exposure to cold temperatures triggers the clinical manifestations.

  Currently, there is no authorised medicinal product available to treat CAgD. 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 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 effects triggered by BIVV009 compared to placebo (similar to the study drug without the active component) . 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 following randomization will receive either BIVV009 or placebo every two weeks by intravenous infusion during a 25 week period.
  -Part B open-label period as a long-term safety and response durability phase, where patients at the end of the part A period will receive 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.

  There will be about 40 subjects participating in this study including approximately 4 from UK.

  Summary of Results

  BIVV009-04 (this study) participants first received sutimlimab or placebo in a 1:1 allocation (Part A) followed by an open-label period (Part B) where everyone received sutimlimab, and designed to evaluate the efficacy and safety of sutimlimab in symptomatic patients with primary Cold Agglutinin Disease (CAD) with no recent history of blood transfusion.
  The results of Part B of this study demonstrated that sutimlimab continues to prevent hemolysis and improves anemia during the extended treatment duration in Part B in both groups of patients. The favorable effect on the markers of hemolysis in patients who switched from placebo reached the extent seen in patients who continued sutimlimab within the first weeks of treatment in Part B. Effects on bilirubin, hemoglobin, and FACIT-Fatigue were maintained throughout the treatment period in patients who continued sutimlimab and in patients who switched from placebo to sutimlimab were maintained after the favorable effect of sutimlimab was achieved. The 9-week safety follow-up (SFU) period following the final dose of sutimlimab, showed that sutimlimab was generally well tolerated. One fatal Treatment Emerging Serious Adverse Effect (TESAE) of squamous cell carcinoma of lung was reported. Treatment with sutimlimab was discontinued in this subject due to this event. The patient later died due to the event approximately 50 days after the last dose of sutimlimab. The event was assessed as not related to sutimlimab by the Investigator.
  In Part B, the type and frequency of TEAEs were generally consistent with the underlying disease indication, reported medical history, and an older medically complex patient population. During the 9-week SFU period, most TEAEs were attributed to worsening of underlying CAD.
  No TEAEs suggestive of serious hypersensitivity or anaphylactic reactions associated with sutimlimab administration were reported. Two thromboembolic events assessed as nonserious and non-related TEAEs were reported.
  Identified clinically significant laboratory abnormalities were generally consistent with the underlying disease indication or other screening/baseline values or were transient/intermittent in nature. No patterns or trends were observed.
  Only minimal interruption of the conduct of the study due to the COVID-19 pandemic occurred and this was considered to have no impact on the analyses.
  In conclusion, the results of Part B of the study demonstrate sustained inhibition of hemolysis, favorable effect on Quality Of Life and acceptable safety profile for sutimlimab, which supports the long-term positive risk-benefit profile of sutimlimab for the treatment of hemolysis in patients with CAD.

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  17/LO/1921

• Date of REC Opinion

  26 Feb 2018

• REC opinion

  Further Information Favourable Opinion