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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

1 Sep 2022 → ongoing

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2023-510346-25-00

EudraCT number

2021-005692-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacogenetic, Efficacy, Pharmacokinetic, Safety, Pharmacodynamic, Therapy

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

Secondary objectives 1

1. To assess supportive evidence of the efficacy of depemokimab SC versus placebo on multiple clinical outcomes in participants with uncontrolled HES receiving SoC

Conditions and MedDRA coding

Hypereosinophilic Syndrome (HES)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Pharmaceuticals And Medical Devices Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient level data (PID) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at : https://www.gsk.com/en-gb/innovation/trials/data-transparency/ Supporting information: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR). Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications. Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for initial period of 12 months but an extension may be granted, when justified, for up to 6 months. URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 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.
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 <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.
6. 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.

Exclusion criteria 22

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. 13 - 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) is 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, based on investigator's discretion.
14. 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.
15. Non oral systemic corticosteroids: Participants who have received intravenous, intramuscular, or subcutaneous corticosteroids within 4- weeks prior to Visit 2.
16. 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.
17. 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.
18. ECG Assessment: QTcF ≥450 msec or QTcF ≥480 msec for participants with Bundle Branch Block at Screening Visit 1.
19. OCS responsiveness: Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
20. Alcohol/Substance Abuse
21. Pregnancy
22. Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of HES flares during the 52-week study intervention period

Secondary endpoints 4

1. Time to first HES flare (days)
2. At least one HES flare during the 52-week study intervention period
3. Change from Baseline to Week 52 in Brief Fatigue Inventory (BFI) item 3 weekly average score.
4. Change from Baseline to Week 24 in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 16

Locations

9 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 342 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications