Hypereosinophilic Syndrome (HES) MedDRA version: 20.0 Level: PT Classification code 10048643 Term: Hypereosinophilic syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Depemokimab
Product Code: [GSK3511294]
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Depemokimab
CAS Number: 2243274-14-6
Current Sponsor code: GSK3511294
Con
Sponsors
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be =18 years of age, at the time of signing the informed consent. 2. Participants who are =40 kg at Screening Visit 1. 3. 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 4. 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 one 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. 5. 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 =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. 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. 14 - 16. 2. 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. 3. 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. 4. 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. 5. 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) are acceptable if participant otherwise meets entry criteria. 6. Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. 7. 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. 8. Eosinophilia of unknown significance: Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction. 9. Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). 10. 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. 11. 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. 12. 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. 13. Monoclonal antibodies (mAb) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy. 14. mAbs: Participants who have received mAb within 30 days or 5 half-lives, whichever is longer, prior to Visit 1. If a participant has been treated with and responsive to bi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of depemokimab subcutaneous (SC) given every 6 months versus placebo in participants with uncontrolled HES receiving standard of care (SoC);Secondary Objective: To assess supportive evidence of the efficacy of depemokimab SC given every 6 months versus placebo on multiple clinical outcomes in participants with uncontrolled HES receiving SoC;Primary end point(s): Frequency of HES flares during the 52-week study intervention period;Timepoint(s) of evaluation of this end point: Defined within the primary endpoint description | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to first HES flare (days) • At least one HES flare during the 52-week study intervention period • Change from Baseline to Week 52 in weekly average score of Brief Fatigue Inventory (BFI) item 3;Timepoint(s) of evaluation of this end point: Defined within the secondary endpoints description | — |
Countries
Argentina, Australia, Belgium, Brazil, China, Czechia, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Limited
Outcome results
None listed