PDY16370-CAD

• Research type

  Research Study

• Full title

  A multicenter, phase 1b, open label, nonrandomized, single dose study evaluating the safety, tolerability and activity of BIVV020 in adults with cold agglutinin disease.

• IRAS ID

  272817

• Contact name

  Martin A. Solberg

• Contact email

  Martin.Solberg@sanofi.com

• Sponsor organisation

  Bioverativ USA Inc.

• Eudract number

  2019-001844-22

• Duration of Study in the UK

  2 years, 0 months, 1 days

• Research summary

  Summary of Research

  Cold agglutinin disease is an autoimmune haemolytic anaemia caused by IgM-induced CP activation.

  BIVV020 is a humanized monoclonal antibody that binds to and selectively inhibits the activated form of human serine protease complement component 1, s subcomponent (C1s). BIVV020 is a second generation classical complement inhibitor.

  This study will provide clinical data on the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BIVV020 in adults with CAD to facilitate the dose/dosing regimen selection for future clinical studies with BIVV020. The starting dose for this study is based on nonclinical data and will be further supported by an ongoing single dose study in healthy human volunteers.

  Summary of Results

  1) General information about the study Why the study was done?
  In this study, researchers wanted to find out how safe and tolerable a single dose of SAR445088 is after it was given as an intravenous (into the vein) infusion to adults with CAD, and to see whether it had any effect on the disease.

  What is the complement system or complement?
  The complement system is part of what is known as the innate immune system and consists of a network of many different proteins. When complement proteins are activated, this system helps to clear from the body causes of infections.

  What is cold agglutinin disease?
  Cold agglutinin disease is a disease that occurs when complement proteins are inappropriately activated. Under low environmental temperature, proteins (cold agglutinins) are activated by the complement system. The cold agglutinins then bind to red blood cells and form clumps, which will cause red blood cells to break down.

  Where and when the study took place
  This study took place in Germany, Italy, Netherlands, Norway, and United Kingdom. It started in June 2020 and ended in December 2021.

  Who took part in the study?
  Who was allowed to take part in the study Both men and women were allowed to participate in the study:
  • Be 18 years or older
  • Had cold agglutinin disease
  • Had a low level of oxygen-carrying protein (hemoglobin) in blood
  • Had a high level of byproduct of red blood cell breakdown (bilirubin)
  • Had been vaccinated against diseases that could happen when the complement system is blocked (SAR445088 affects the complement system)

  Who was not allowed to take part in the study People were not allowed to participate in the study if they had at least one of the following:
  • If the cold agglutinin disease of this person was caused by an infection, another autoimmune disease called rheumatological disease, serious blood problems, or cancer.
  • If he/she had any infection within 1 month before screening
  • If he/she had an autoimmune disease called systemic lupus erythematosus

  About the people who took part in the study In total, 12 people took part:
  • In the group of people taking dose 1, they were from:
  - Germany: 3 people
  - Italy: 1 people
  - Norway: 1 people
  - United Kingdom: 1 people
  • In the group of people taking dose 2, they were from:
  - Italy: 1 people
  - Netherlands: 3 people
  - United Kingdom: 2 people

  3) What medicines were studied?
  About the study medicine [SAR445088]
  This is a new medicine being developed. It is designed to treat cold agglutinin disease (CAD, a rare autoimmune disease where the body’s natural guard system mistakenly attacks blood cells and causes red blood cells to break down). SAR445088 is designed to block a part of the complement system and prevent the damage to the red blood cells.

  How was the medicine given?
  This study was “open label”. This means that both the people taking part and the study doctors knew who was given which dose of SAR445088. The medicine was injected directly into the vein.

  Doses tested:
  In this study, dose 1 or dose 2 were given as a single dose to people by the intravenous route.

  4) What were the side effects?
  Different methods for presenting safety data exist. In this summary, we use the method required by the European Medicines Agency for this sort of document. We summarize the side effects that happened during the study. This means that we describe the health problems that people had and that the study doctor thought might be related to the medicine used in the study (including the dummy medicine). Study results are also presented in other places, and available to the public, using different reference methods.

  What are “medical problems” and “side effects”?
  Researchers looked at both of these during this study:
  • New medical problems - all problems related to someone’s health (for example, a headache) that happen after the study has started. The study doctor does not know if it has been caused by the study medicine or caused by something else.
  • Side effects - These are health problems that happen to a study participant during the course of the study. These health problems are called “side effects” because the study doctor thinks they might be related to the medicine used in the study.

  What did the study find out?
  In this study, researchers looked at the numbers of participants who had one or more new medical problems after having taken SAR445088. In total, all 6 people (100%) in the group taking dose 1 had new medical problems, and 5 people (83%) in the group taking dose 2 had new medical problems.

  How many people had side effects?
  In this study, 3 out of 6 people (50%) in the group taking dose 1 had side effects, none of the people in the group taking dose 2 had any side effects.

  Were any of the side effects serious?
  A side effect is considered serious if it:
  • leads to death or is life-threatening, or
  • causes the study participant to go to the hospital or to stay longer in the hospital, or
  • causes permanent damage, or
  • causes a health problem in the study participant’s baby, or
  • is considered as an important medical problem putting the study participant in danger.
  In this study, none of the side effects were considered serious.

  What were the most common non-serious side effects?
  The most common non-serious side effect in people taking dose 1 was blue lips (2 out of 6 people, 33%). None of people taking dose 2 had any non-serious side effects.

  What do these results tell us?
  These results show that SAR445088 was generally safe and well tolerated at a single dose of dose 1 and dose 2 in people with cold agglutinin disease.

  5) How has this study helped people?
  In this study, researchers wanted to find out if medicine SAR445088 could be used safely, that the participants tolerated the drug well without causing too many side effects, and whether it had any effect on the disease itself. The medicine was tested on adults with cold agglutinin disease.

  Overall, the results suggested that generally SAR445088 was safe and well tolerated by people during the time they took the medicine. The results also showed an increase in hemoglobin levels as well as decreased levels of bilirubin in most of the study participants.

  6) Where can I find more information about this study?
  Results of clinical studies may be available to the public in different places, and in many countries. As explained in Section 4, study results presented in other places use different reference methods.

  If you want more information, and if it is available, then you will need to use the study reference numbers. The list below provides those numbers, used by different organizations around the world:
  Study number: PDY16370
  Sponsor product code: SAR445088
  EudraCT number: 2019-001844-22
  ClinicalTrials.gov identifier: NCT04269551 Investigational New Drug (IND) number: 143193 World Health Organization (WHO) Universal Trial Number (UTN): U1111-1233-0831

  More information on this study may be found by performing an internet search in available search engine(s), with study identifier PDY16370.

  7) Who sponsored this study?
  Sponsor: Sanofi

• REC name

  London - London Bridge Research Ethics Committee

• REC reference

  20/LO/0163

• Date of REC Opinion

  20 Apr 2020

• REC opinion

  Further Information Favourable Opinion