Phase 3 paediatric study of Avatrombopag in Immune Thrombocytopenia

  • Research type

    Research Study

  • Full title

    A Phase 3b, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial with an Open-label Extension Phase to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Thrombocytopenia in Pediatric Subjects with Immune Thrombocytopenia for ≥6 Months

  • IRAS ID

    1003418

  • Contact name

    John Grainger

  • Contact email

    John.Grainger@mft.nhs.uk

  • Sponsor organisation

    Dova Pharmaceuticals, Inc.

  • Eudract number

    2020-003232-24

  • Clinicaltrials.gov Identifier

    NCT04516967

  • Research summary

    Lay summary of study results: Researchers were looking for a way to treat a condition called primary immune thrombocytopenia (ITP). Immune thrombocytopenia (ITP) is a rare blood disorder that causes a shortage of platelets in the blood. Platelets are blood cells that help stop bleeding. With ITP, the body’s defense system called the immune system mistakes the platelets for foreign substances and destroys the platelets.

    There are 2 types of ITP:
    • With Primary ITP, low platelet count is not caused by another disease.
    • With Secondary ITP, low platelet count is caused by another disease or condition (such as an infection).
    People with a low platelet count may have problems such as getting a bruise easily, nosebleeds, or bleeding gums. They may also feel tired and have a hard time with daily life or school activities.

    In this study, researchers wanted to find out if avatrombopag, the test drug, is safe and can help with low platelets caused by primary ITP in young people (1 to 17 years old).

    At the start of this study, avatrombopag had been approved in Europe and the United States of America (USA) to treat certain types of thrombocytopenia (low platelet count) in adults.

    This study was done in 2 parts. Each part had its own main goal.
    • Part 1: To find out if avatrombopag given for up to 12 weeks could lead to a higher platelet count than placebo
    The placebo looked like avatrombopag but did not contain any medication.
    Part 1 results led to avatrombopag getting approved in the USA to treat ITP in children (from 1 year old and above).

    • Part 2: To find out if avatrombopag given for up to 2 years is safe
    This report includes the results of Part 2 of the study.

    Participants took avatrombopag or placebo in Part 1 for up to 12 weeks by mouth. Then, researchers checked if participants met the requirements to join Part 2.
    All participants took avatrombopag by mouth for up to 2 years in Part 2.

    Participants had health checks to monitor their safety. The study doctors asked how the participants were feeling and took their blood samples for testing.

    People could join the study if they met all the study requirements, such as:
    • They were between 1 year and 17 years old before starting Part 1.
    • They had primary ITP lasting for 6 months or longer and a recent blood test that showed fewer than 30,000 platelets per microliter of blood. Microliter is a unit of measurement.

    A total of 75 participants joined Part 1 and received avatrombopag or placebo. The study took place in Europe and North America. A total of 73 participants continued to Part 2 and received avatrombopag for 2 years.

    The most common side effects in Part 2 were:
    • Headache in 3 out of 73 participants (4%)
    • Pain in the belly in 2 out of 73 participants (3%)
    • Nausea (feeling sick) in 2 out of 73 participants (3%)
    • Too many platelets in the blood in 2 out of 73 participants (3%)

    A total of 3 participants did not finish Part 2 because of side effects. These side effects were:
    • Blood clot in the deep veins in the body (deep vein thrombosis or DVT) − 1 participant
    • Feeling of tingling or numbness (“pins and needles”) and difficulty speaking because of weak speech muscles − 1 participant
    • Disorder of the bone marrow (soft tissue in the bones) and a blood test that showed high levels of 2 proteins called “lactate dehydrogenase” and “aspartate aminotransferase” (high levels of these proteins could be a sign of liver irritation) − 1 participant

    The most common serious side effect in Part 2 was too many platelets in the blood. This was seen in 2 out of 73 participants (3%).
    No participant died during the study.

    In Part 2, researchers found that avatrombopag was safe and well tolerated when taken for up to 2 years by participants 1 year to 17 years old with primary ITP lasting for 6 months or longer.

    Immune thrombocytopenia is a condition where there is a shortage of blood cells called
    platelets due to the body’s immune system attacking and destroying these cells. Platelets
    are needed for normal blood clotting. Avatrombopag is a medication that is approved in
    Europe and the USA to treat certain types of thrombocytopenia in adults, but in this study
    we would like to test the medicine in children and young adults to see how well it works
    and how safe it is. There remains an unmet medical need for new treatment options for
    paediatric patients with this condition.
    The study is planned to involve 72 children and young adults who have immune
    thrombocytopenia.
    Depending on the participant’s age the study medication will be given as either a tablet
    or a powder to be added to food or drink. The study will be conducted in 2 parts. In the
    first part of the study (called the Core Phase) participants will receive either
    avatrombopag or placebo in a 3:1 ratio. In the second part of the study (called the
    Extension Phase) all participants will receive avatrombopag.
    Participation in the study will last for a total of up to 29 months (i.e. 2 years and 5
    months).
    The Core Phase lasts for up to 5 months. In this part of the study participants will be
    asked to visit the study site twice in the first week, and then every week for 12 weeks.
    Participants will be asked to take the study medicine during this 12 week period.
    If participants enter the Extension Phase, after they complete treatment in the Core
    Phase they will immediately begin the Extension Phase. Participants will be asked to visit
    the study site every month for 2 years. Participants will be asked to take the study
    medicine during this period.

  • REC name

    London - Westminster Research Ethics Committee

  • REC reference

    20/LO/1195

  • Date of REC Opinion

    30 Dec 2020

  • REC opinion

    Further Information Favourable Opinion