OCEAN (depemOkimab effiCacy Eosinophilic grAnulomatosis with polyaNgiitis)

Overview

About this study

The primary objective of the study is to evaluate the effectiveness of depemokimab 200 mg SC every 26 weeks compared with mepolizumab 300 mg SC every 4 weeks in participants with relapsing or refractory EGPA receiving Standard of Care (SoC) therapy with the endpoint of remission (i.e., a Birmingham Vasculitis Activity Score (BVAS)=0 and a dose of oral corticosteroids (OCS) ≤ 4mg/day) at both Week 36 and Week 52.

The aim of this study is to investigate the effectiveness and safety of depemokimab 200 mg (administered as 100 mg x 2) SC injections every 26 weeks compared with mepolizumab 300 mg (administered as 100 mg x 3) SC injections every 4 weeks in participants with relapsing or refractory EGPA receiving SoC therapy, over a 52-week intervention period.

Depemokimab is a humanised, affinity matured monoclonal antibody that blocks human interleukin-5 (IL-5) binding to its receptor. Depemokimab is being developed as a long‑acting subcutaneous injectable anti-IL-5 (anti-IL-5) therapy and is expected to deliver an efficacy and safety profile similar to the current anti-IL-5 therapies with a reduced dosing frequency (once every 26 weeks).

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 07/03/2024. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ulrich Specks, M.D.

Open for enrollment

Contact information:

Michael Stachowitz

(507) 284-4862

Stachowitz.Michael@mayo.edu

More information

Publications

Publications are currently not available