Clinical trial NCT05263934: Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA)
Official title: A 52-week, Randomized, Double-blind, Double-dummy, Parallel-group, Multi-centre, Non-inferiority Study to Investigate the Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA) Receiving Standard of Care (SoC) Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Eosinophilic Granulomatosis With Polyangiitis
Keywords: Depemokimab
Mepolizumab
Eosinophilic Granulomatosis with Polyangiitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-03-03
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive either depemokimab plus placebo matching mepolizumab or mepolizumab plus placebo matching depemokimab
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory EGPA receiving SoC therapy.


Eligibility criteria: Inclusion Criteria:

* Participant (male or female) must be 18 years of age or older at the time of signing the informed consent.
* Participants who are \>=40 kilogram at Screening Visit 1.
* Participants with a documented diagnosis of EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia defined as \>1.0\*10\^9/Liter (L) and/or \>10 percentage (%) of leucocytes plus at least 2 of the following additional features of EGPA: a biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation, neuropathy, mono or poly (motor deficit or nerve conduction abnormality), pulmonary infiltrates, non-fixed, sino-nasal abnormality, cardiomyopathy (established by echocardiography or magnetic resonance imaging), glomerulonephritis (hematuria, red cell casts, proteinuria), alveolar hemorrhage (by bronchoalveolar lavage), palpable purpura, anti-neutrophil cytoplasmic antibodies positive Myeloperoxidase or Proteinase 3.
* History of relapsing OR refractory disease.
* Participants must be on a stable dose of oral prednisolone or prednisone of \>=7.5 mg/day (but not \>50 mg/day) for at least 4 weeks prior to Baseline (Visit 2).
* If participants receiving immunosuppressive therapy (excluding cyclophosphamide) the dosage must be stable for the 4 weeks prior to Baseline (Visit 2) and during the study.
* 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) OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1%.
* Capable of giving signed informed consent

Exclusion Criteria:

* Participants diagnosed with granulomatosis with polyangiitis; previously known as Wegener's granulomatosis or microscopic polyangiitis.
* Participants with organ-threatening EGPA as per EULAR criteria,
* Imminently life-threatening EGPA disease within 3 months prior to Screening (Visit 1).
* A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening.
* Participants with alanine aminotransferase \>2\*upper limit of normal (ULN) or if participant is on background methotrexate or azathioprine \>3\*ULN, aspartate aminotransferase \>2\*ULN or if participant is on background methotrexate or azathioprine \>3\*ULN, alkaline phosphatase \>=2.0\*ULN, total bilirubin \>1.5\*ULN (isolated bilirubin \>1.5\*ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%), 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 who have known, pre-existing, clinically significant system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
* Clinically significant abnormality in the hematological, biochemical or urinalysis screen at Visit 1.
* Chronic or ongoing active infectious disease requiring systemic treatment.
* Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
* A known immunodeficiency (e.g. human immunodeficiency virus \[HIV\]).
* Participants that, according to the investigator's medical judgment, are likely to have active coronavirus disease 2019 (COVID-19) infection. 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.
* Participants with a known allergy or intolerance to a monoclonal antibody or biologic therapy or any of the excipients of the investigational products.
* Participants who have a previous documented failure with anti-Interleukin-5 /Interleukin-5 receptor therapy. Participants who have received monoclonal antibodies (mAb) and who have not undergone the required washout periods, prior to Visit 1.
* Participants receiving any of the following: Oral corticosteroids: Participant requires an oral corticosteroid dose of \>50 mg/day prednisolone/prednisone in the 4-week period prior to Baseline (Visit 2), Intravenous (IV), intramuscular or subcutaneous (SC) corticosteroids in the 4-week period prior to Baseline (Visit 2), Omalizumab within 130 days prior to Screening (Visit 1), Cyclophosphamide (CYC): oral CYC within 4 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks prior to Baseline (Visit 2), if their total white blood cells is \>=4\*10\^9/L (measured using the local laboratory if necessary), Rituximab within 12 months prior to Screening (Visit 1); in addition, the Participant must have shown recovery of peripheral B-cell count to within the normal range, Tezepelumab and Dupilumab with a washout period of 5 half-lives prior to Screening Visit 1, IV or SC immunoglobulin within 6 months prior to Screening (Visit 1); For China and Japan only within 12 weeks prior to Screening (Visit 1), Interferon-alpha within 6 months prior to Screening Visit 1, Anti-tumor necrosis factor therapy within 12 weeks prior to Screening Visit 1, Anti-CD52 (alemtuzumab) within 6 months prior to Screening Visit 1.
* Participants with 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 in the 12-lead ECG central over-read from at Screening Visit 1.

Primary outcomes:
measure: Number of participants with remission (Birmingham Vasculitis Activity Score [BVAS] =0 and a dose of oral corticosteroid [OCS] less than or equal to [<=] 4 milligram [mg] per day)
timeFrame: Up to Week 52
Secondary outcomes:
measure: Number of participants in each category of accrued duration of remission
timeFrame: Up to Week 52
measure: Number of participants with total accrued duration of remission
timeFrame: Up to Week 52
measure: Time to first EGPA relapse
timeFrame: Up to Week 52
measure: Number of participants receiving in each category of mean OCS dose during the last 4 weeks of study treatment period (Weeks 49 to 52)
timeFrame: Weeks 49 to 52
measure: Number of participants achieving remission (BVAS = 0 and OCS <= 4mg/day) within the first 24 weeks with continued remission until Week 52
timeFrame: Up to Week 52
measure: Number of participants achieving remission using the European League against Rheumatism (EULAR) definition (BVAS = 0 and OCS <=7.5 mg/day) at Weeks 36 and 52
timeFrame: At Weeks 36 and 52
measure: Number of participants in each category of accrued duration of remission according to the EULAR definition of remission (BVAS = 0 plus OCS <=7.5 mg/day) over 52-week intervention period
timeFrame: Up to Week 52
measure: Number of participants with total accrued duration of remission according to the EULAR definition of remission
timeFrame: Up to Week 52
measure: Number of participants with remission (BVAS=0 and OCS <=7.5 mg/day) within the first 24 weeks with continued remission until Week 52
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Florida
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: San Miguel de Tucuman
country: Argentina
facility: GSK Investigational Site
city: Graz
country: Austria
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Beijing
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Hefei
country: China
facility: GSK Investigational Site
city: Kunming
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Qingdao
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shenyang
country: China
facility: GSK Investigational Site
city: Shenzhen
country: China
facility: GSK Investigational Site
city: Wenzhou
country: China
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha 8
country: Czechia
facility: GSK Investigational Site
city: Brest Cedex
country: France
facility: GSK Investigational Site
city: La Roche Sur Yon
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Montpellier cedex
country: France
facility: GSK Investigational Site
city: Nantes Cedex 1
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Suresnes
country: France
facility: GSK Investigational Site
city: Toulouse Cedex 9
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Bari
country: Italy
facility: GSK Investigational Site
city: Brescia
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Pisa
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Torrette AN
country: Italy
facility: GSK Investigational Site
city: Treviso
country: Italy
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
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: 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: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Leiden
country: Netherlands
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Malmo
country: Sweden
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: