Depemokimab in Participants With Hypereosinophilic Syndrome, Efficacy, and Safety Trial

Official title

A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Depemokimab in Adults With Hypereosinophilic Syndrome (HES)

Overview

This is a 52-week, randomized, placebo-controlled, double-blind, parallel group, multicenter study of depemokimab in adults with uncontrolled HES receiving standard of care (SoC) therapy. The study will recruit patients with a confirmed diagnosis of HES and who are on stable HES therapy for at least 4 weeks prior to randomization (Visit 2). Eligible participants must have uncontrolled HES with a history of repeated flare (≥2 flares in the previous 12 months) and blood eosinophil count of ≥1,000 cells/ microliter (μL) during Screening. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an escalation in therapy. Participants who meet the inclusion and exclusion criteria will be randomized in a 2:1 ratio to receive either depemokimab or placebo while continuing their SoC HES therapy.

Interventions

• Drug Depemokimab
  Depemokimab will be administered.
• Other Placebo
  Matching placebo will be administered.

Primary outcome measures

• Frequency of HES flares [Time frame: Up to 52 weeks]

Secondary outcome measures (3)

• Time to first HES flare [Time frame: Up to 52 weeks]
• Number of participants with at least one HES flare during the 52-week study intervention period [Time frame: Up to 52 weeks]
• Change from Baseline to Week 52 in weekly average score of Brief Fatigue Inventory (BFI) item 3 (worst fatigue in last 24 hours) [Time frame: Baseline and up to Week 52]

Eligibility criteria

Inclusion criteria

• Participants who are greater than or equal (>=) 40 kilogram (kg) at Screening Visit 1.
• Participants who have a documented diagnosis of HES prior to Visit 2.
• A history of 2 or more HES flares within the past 12 months prior to Visit 1.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a) woman of non-childbearing potential (WONCBP) Or b) woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of less than (<) 1 percentage (%).
• Capable of giving signed informed consent.

Exclusion criteria

• Participants with 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.
• Participants with chronic or ongoing active infections requiring systemic treatment or a pre-existing parasitic infestation within 6 months prior to Visit 1.
• Participants with a known immunodeficiency (e.g., Human Immunodeficiency Virus \[HIV\]), other than that explained by the use of OCS or other therapy taken for HES.
• 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.
• Cirrhosis or current unstable liver or biliary disease per investigator assessment.
• Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
• Participants with current diagnosis of vasculitis.
• Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction.
• Clinical diagnosis of Eosinophilic granulomatosis with polyangiitis (EGPA).
• Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product.
• Participants who have a previous documented failure with anti-interleukin (IL)-5/5R therapy.
• Participants who have received monoclonal antibodies (mAb) within 30 days or 5 half-lives, whichever is longer, prior to Visit 1.
• Participants who test positive for the FIP1L1-PDGFRα fusion gene.
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) ≥450 milliseconds (msec) or QTcF ≥480 msec for participants with Bundle Branch Block at Screening Visit 1.
• Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
• Participants who are pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 11 centers

• GSK Investigational Site — San Diego
• GSK Investigational Site — Atlanta
• GSK Investigational Site — Boston
• GSK Investigational Site — Southfield
• GSK Investigational Site — Rochester
• GSK Investigational Site — Manhasset
• GSK Investigational Site — Cincinnati
• GSK Investigational Site — Columbus
• … and 3 more centers

Japan · 11 centers

• GSK Investigational Site — Aomori
• GSK Investigational Site — Aomori
• GSK Investigational Site — Chiba
• GSK Investigational Site — Gifu
• GSK Investigational Site — Hyōgo
• GSK Investigational Site — Kanagawa
• GSK Investigational Site — Miyagi
• GSK Investigational Site — Tokyo
• … and 3 more centers

South Korea · 10 centers

• GSK Investigational Site — Gwangju
• GSK Investigational Site — Jeonju
• GSK Investigational Site — Kangwondo
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• … and 3 more centers

China · 9 centers

• GSK Investigational Site — Beijing
• GSK Investigational Site — Changsha
• GSK Investigational Site — Guangzhou
• GSK Investigational Site — Guangzhou
• GSK Investigational Site — Harbin
• GSK Investigational Site — Nanchang
• GSK Investigational Site — Shanghai
• GSK Investigational Site — Suzhou
• … and 1 more center

Italy · 9 centers

• GSK Investigational Site — Bologna
• GSK Investigational Site — Catania
• GSK Investigational Site — Milan
• GSK Investigational Site — Naples
• GSK Investigational Site — Novara
• GSK Investigational Site — Pavia
• GSK Investigational Site — Roma
• GSK Investigational Site — Treviso
• … and 1 more center

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Florida
• GSK Investigational Site — La Plata
• GSK Investigational Site — Mar del Plata
• GSK Investigational Site — Quilmes

Brazil · 4 centers

• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — Blumenau
• GSK Investigational Site — Rio de Janeiro
• GSK Investigational Site — Sorocaba

Czechia · 4 centers

• GSK Investigational Site — Brno-Bohunice
• GSK Investigational Site — Hradec Králové
• GSK Investigational Site — Prague
• GSK Investigational Site — Ústí nad Labem

Mexico · 3 centers

• GSK Investigational Site — Guadalajara
• GSK Investigational Site — Monterrey
• GSK Investigational Site — Veracruz

Romania · 3 centers

• GSK Investigational Site — Bucharest
• GSK Investigational Site — Bucharest
• GSK Investigational Site — Cluj-Napoca

Canada · 2 centers

• GSK Investigational Site — Ottawa
• GSK Investigational Site — Toronto

Germany · 2 centers

• GSK Investigational Site — Bad Bramstedt
• GSK Investigational Site — Mannheim

Greece · 2 centers

• GSK Investigational Site — Athens
• GSK Investigational Site — Rio Patras

Israel · 2 centers

• GSK Investigational Site — Ramat Gan
• GSK Investigational Site — Tel Aviv

Poland · 2 centers

• GSK Investigational Site — Chęciny
• GSK Investigational Site — Lodz

Australia · 1 center

• GSK Investigational Site — Garran

Belgium · 1 center

• GSK Investigational Site — Brussels

Denmark · 1 center

• GSK Investigational Site — Odense C

Hong Kong · 1 center

• GSK Investigational Site — Pokfulam

United Kingdom · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05334368 · 217013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗