Phase 3 Study of Ravulizumab in Thrombotic Microangiopathy Associated with a Trigger

  • Research type

    Research Study

  • Full title

    A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants Who Have Thrombotic Microangiopathy Associated with a Trigger

  • IRAS ID

    1003675

  • Contact name

    Zeeshan Khawaja

  • Sponsor organisation

    Alexion Pharmaceuticals, Inc.

  • Eudract number

    2020-005328-13

  • Clinicaltrials.gov Identifier

    NCT04743804

  • Research summary

    Research Summary

    Thrombotic Microangiopathy (TMA) is a rare, potentially life-threatening condition caused by damage to blood vessels and destruction of the red blood cells and activation of platelets. This results in clots in the small blood vessels, which can damage the kidneys, heart, lungs and brain. TMA can be associated with underlying diseases or ‘triggers’, including infection, autoimmune disease, stem cell transplant, malignant hypertension, organ transplant, drugs, lupus and cancer.

    Current treatment may include withdrawal of conditions that causes the TMA; treatment of symptoms; therapies that reduce the activity of the patient’s immune system; or supportive care including dialysis and transfusions.

    The purpose of this double-blind study is to determine whether treatment with Ravulizumab (which targets part of the complement system that leads to the damage to blood vessels) is effective in treating adult patients with TMA associated with a trigger. Not all of the triggers listed above will be evaluated in this study.

    Participants who meet all eligibility criteria will be randomised in a 1:1 ratio to ravulizumab plus best-support care (BSC) or placebo plus BSC for approximately 6 months (26 weeks). Ravulizumab or placebo will be administered via an intravenous (IV) infusion on 4 separate occasions during this time.

    The study includes screening assessments, a 26 week treatment period (13 study visits) and a 26 week follow-up period (3 study visits). Assessments include physical examinations, vital signs, an ECG, blood and urine sample collection for testing, a stool sample (or rectal swab) and completion of quality of life questionnaires. If recommended by the study doctor a vaccination against meningitis infection may be given. The total study duration will be up to 54 weeks.

    Approximately 100 participants will participate worldwide (11 - 22 patients from 11 hospitals in the UK).

    Summary of Results

    The information collected in this study was insufficient to show that ravulizumab was more effective than placebo in fully resolving TMA in adult participants. Due to the difficulty of enrolling participants in the study, the decision was made to end the study early with only 16 participants. The study results were inconclusive because the number of participants was too small. The majority of side effects were thought by study doctors to be not related to ravulizumab.
    Complete study results are available to read at the following clinical study register(s):
    www.clinicaltrials.gov
    Use the study number NCT04743804 to search for more information on this website.
    www.clinicaltrialsregister.eu
    Use the study number 2020-005328-13 to search for more information on this website.

  • REC name

    East of Scotland Research Ethics Service REC 2

  • REC reference

    21/ES/0041

  • Date of REC Opinion

    12 May 2021

  • REC opinion

    Further Information Favourable Opinion