A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Depemokimab in Adults With Hypereosinophilic Syndrome (HES)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 109
- 试验地点
- 94
- 主要终点
- Frequency of HES flares
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This will be a double-blind study with respect to allocation of depemokimab or placebo to participants. All site staff, participants, and investigator will be blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who are greater than or equal (>=) 40 kilogram (kg) at Screening Visit
- •Participants who have a documented diagnosis of HES prior to Visit
- •A history of 2 or more HES flares within the past 12 months prior to Visit
- •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.
排除标准
- •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
- •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
- •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
- •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
- •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.
研究组 & 干预措施
Placebo
All participants in this arm will receive placebo.
干预措施: Placebo (Other)
Depemokimab
All participants in this arm will receive depemokimab.
干预措施: Depemokimab (Drug)
结局指标
主要结局
Frequency of HES flares
时间窗: Up to 52 weeks
A HES flare is defined as either: a HES-related clinical manifestation based on a physician documented change in clinical signs or symptoms resulting in the need for the following : An increase in the maintenance systemic corticosteroid dose by at least 10 mg/day (prednisone/prednisolone equivalent) for at least 5 days, and/or an increase in or addition of any cytotoxic and/or immunosuppressive HES therapy. OR 2 or more courses of blinded active oral corticosteroid (OCS) during the intervention period. The frequency of HES flares will be calculated for each participant as the number of unique starting dates for HES flares.
次要结局
- Change from Baseline to Week 52 in weekly average score of Brief Fatigue Inventory (BFI) item 3 (worst fatigue in last 24 hours)(Baseline and up to Week 52)
- Time to first HES flare(Up to 52 weeks)
- Number of participants with at least one HES flare during the 52-week study intervention period(Up to 52 weeks)