Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA)

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Brief Title

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

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.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

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)

Secondary Outcome

 Number of participants in each category of accrued duration of remission

Condition

Eosinophilic Granulomatosis With Polyangiitis

Intervention

Depemokimab

Study Arms / Comparison Groups

 Participants receiving depemokimab+placebo matching mepolizumab
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

160

Start Date

June 10, 2022

Completion Date

November 7, 2025

Primary Completion Date

October 10, 2025

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 who have been diagnosed with 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 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, 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 at Screening Visit 1.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

GSK Clinical Trials, 877-379-3718, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05263934

Organization ID

217102


Responsible Party

Sponsor

Study Sponsor

GlaxoSmithKline


Study Sponsor

GSK Clinical Trials, Study Director, GlaxoSmithKline


Verification Date

May 2022