Authorised Therapeutic confirmatory (Phase III) Hypereosinophilic Syndrome (HES)

A study to Investigate the efficacy and safety of Depemokimab compared with placebo in Adults with Hypereosinophilic Syndrome (HES)

EU CTIS ID: 2023-510346-25-00

What this study is testing

To evaluate the efficacy of depemokimab subcutaneous (SC) versus placebo in participants with uncontrolled HES receiving standard of care (SoC)

  • Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Participant must be ≥18 years of age, at the time of signing the informed consent.
  • Participants who are ≥40 kg at Screening Visit 1.
  • Participants who have a documented diagnosis of HES prior to Visit 2. HES diagnosis is based on: • blood eosinophilia of >1,500 eosinophils/μL on at least 2 occasions at ≥1 month interval, without a discernible non haematological secondary cause, and • signs or symptoms of organ involvement and/or dysfunction that can be directly related to eosinophilia
  • Flare history: A history of 2 or more HES flares within the past 12 months prior to Visit 1. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an addition or escalation in OCS or cytotoxic/immunosuppressive therapy. At least 1 HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
  • Male or female participants • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of non-childbearing potential (WONCBP) as defined in protocol Section 10.4, Appendix 4 OR • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in, Section 10.4, Appendix 4, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
  • Capable of giving signed informed consent as described in protocol Section 10.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

You likely can't join if

  • HES disease manifestations which in the opinion of the Investigator may put the participant at unacceptable risk from study participation or confound interpretation of efficacy or safety data. Specific consideration should be given to the participant's ability to comply with protocol requirements, including the list of prohibited therapies; exclusion criteria no. 13 - 16.
  • COVID-19: Participants that, according to the Investigator's medical judgment, are likely to have active COVID-19 infection should be excluded. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
  • Other concurrent medical conditions that may affect the participant's safety: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, cardiac or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
  • Hypersensitivity: Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product in protocol Section 6.1.
  • Monoclonal antibodies (mAb) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy, based on investigator's discretion.
  • mAbs: Participants who have received mAb within 30 days or 5 halflives, whichever is longer, prior to Visit 1 (other than approved mAbs for the treatment of COVID-19). If a participant has been treated with and responsive to biologics for HES, the participant should not stop the treatment for study eligibility purpose.
See the full eligibility criteria
Who can join
  • Participant must be ≥18 years of age, at the time of signing the informed consent.
  • Participants who are ≥40 kg at Screening Visit 1.
  • Participants who have a documented diagnosis of HES prior to Visit 2. HES diagnosis is based on: • blood eosinophilia of >1,500 eosinophils/μL on at least 2 occasions at ≥1 month interval, without a discernible non haematological secondary cause, and • signs or symptoms of organ involvement and/or dysfunction that can be directly related to eosinophilia
  • Flare history: A history of 2 or more HES flares within the past 12 months prior to Visit 1. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an addition or escalation in OCS or cytotoxic/immunosuppressive therapy. At least 1 HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
  • Male or female participants • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of non-childbearing potential (WONCBP) as defined in protocol Section 10.4, Appendix 4 OR • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in, Section 10.4, Appendix 4, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
  • Capable of giving signed informed consent as described in protocol Section 10.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
What rules you out
  • HES disease manifestations which in the opinion of the Investigator may put the participant at unacceptable risk from study participation or confound interpretation of efficacy or safety data. Specific consideration should be given to the participant's ability to comply with protocol requirements, including the list of prohibited therapies; exclusion criteria no. 13 - 16.
  • COVID-19: Participants that, according to the Investigator's medical judgment, are likely to have active COVID-19 infection should be excluded. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
  • Other concurrent medical conditions that may affect the participant's safety: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, cardiac or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
  • Hypersensitivity: Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product in protocol Section 6.1.
  • Monoclonal antibodies (mAb) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy, based on investigator's discretion.
  • mAbs: Participants who have received mAb within 30 days or 5 halflives, whichever is longer, prior to Visit 1 (other than approved mAbs for the treatment of COVID-19). If a participant has been treated with and responsive to biologics for HES, the participant should not stop the treatment for study eligibility purpose.
  • Non oral systemic corticosteroids: Participants who have received intravenous, intramuscular, or subcutaneous corticosteroids within 4- weeks prior to Visit 2.
  • Investigational medications/clinical study: • Participants who have received treatment with an investigational agent within 30 days or 5 drug half-lives whichever is longer, prior to Visit 1. The term "investigational" applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products. • Participants who are currently participating in any other interventional clinical study.
  • FIP1L1-PDGFRα Status: Participants who test positive for the FIP1L1-PDGFRα fusion gene (i.e., participants with the myeloid-variant HES are excluded). Blood sampling is required for all participants at Screening (Visit 1) for this test unless the documented result is available.
  • ECG Assessment: QTcF ≥450 msec or QTcF ≥480 msec for participants with Bundle Branch Block at Screening Visit 1.
  • OCS responsiveness: Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
  • Infection: • Participants with chronic or ongoing active infections requiring systemic treatment. • Participants with a pre-existing parasitic infestation within 6 months prior to Visit 1.
  • Alcohol/Substance Abuse
  • Pregnancy
  • Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
  • Immunodeficiency: Participants with a known immunodeficiency (e.g., HIV), other than that explained by the use of oral corticosteroid (OCS) or other therapy taken for HES.
  • Malignancy: • Participants with a history of or current lymphoma. • Participants with current malignancy or previous history of cancer in remission for less than 5 years prior to Visit 1. Participants that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded. • Participants with a haematologic malignancy with hypereosinophilia in which HES is not the primary diagnosis, e.g., chronic myeloid leukaemia, myelodysplastic syndrome, chronic eosinophilic leukaemia-not otherwise specified.
  • Liver disease: • Cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice. NOTE: Stable non cirrhotic chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) is acceptable if participant otherwise meets entry criteria.
  • Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
  • Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at Screening will be evaluated and current vasculitis must be excluded prior to randomization.
  • Eosinophilia of unknown significance: Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction.
  • Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA).

The study team makes the final eligibility decision.

Where it's taking place

  • Israel
  • Argentina
  • Korea, Republic of
  • Canada
  • United States
  • Hong Kong
  • United Kingdom
  • Mexico
  • Japan
  • China
  • Australia
  • Brazil

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Israel; Argentina; Korea, Republic of; Canada; United States; Hong Kong and 6 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.