Clinical trial NCT05334368: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hypereosinophilic Syndrome
Keywords: Depemokimab
Hypereosinophilic Syndrome
DESTINY
Monoclonal antibody
Anti-interleukin -5
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-04-19
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study.
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Frequency of HES flares
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Time to first HES flare
timeFrame: Up to 52 weeks
measure: Number of participants with at least one HES flare during the 52-week study intervention period
timeFrame: Up to 52 weeks
measure: Change from Baseline to Week 52 in weekly average score of Brief Fatigue Inventory (BFI) item 3 (worst fatigue in last 24 hours)
timeFrame: Baseline and up to Week 52
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Southfield
country: United States
facility: GSK Investigational Site
state: Michigan
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: Quilmes
country: Argentina
facility: GSK Investigational Site
city: Garran
country: Australia
facility: GSK Investigational Site
state: Australian Capital Territory
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Blumenau
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Sorocaba
country: Brazil
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Changsha
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Harbin
country: China
facility: GSK Investigational Site
city: Nanchang
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Suzhou
country: China
facility: GSK Investigational Site
city: Wuhan
country: China
facility: GSK Investigational Site
city: Brno - Bohunice
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Rio Patras
country: Greece
facility: GSK Investigational Site
city: Pokfulam
country: Hong Kong
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Catania
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Novara
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Treviso
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Aomori
country: Japan
facility: GSK Investigational Site
city: Aomori
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
city: Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Jeonju
country: Korea, Republic of
facility: GSK Investigational Site
city: Kangwondo
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Veracruz
country: Mexico
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: