A Phase 2/3, Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Two-Part Study With Open-Label Extension (OLE) to Assess the Efficacy and Safety of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Ashibio Inc
- 入组人数
- 92
- 试验地点
- 3
- 主要终点
- Number of New HO Lesions as Assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)]
研究概览
简要总结
This study is researching an experimental drug called andecaliximab. The study will include pediatric and adult patients with fibrodysplasia ossificans progressiva (FOP). The study will evaluate how safe and effective andecaliximab is in patients with FOP.
The study is looking at several research questions, including:
- Safety of andecaliximab in participants with FOP
- Whether andecaliximab reduces the number of new heterotopic bone lesions (Heterotopic Ossification; HO)
- Whether andecaliximab reduces the number or severity of flare-ups
- Pharmacokinetics/pharmacodynamics (PK/PD): How much study drug is in your blood at different times and its impact on blood biomarker(s)
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
详细描述
The ASH-FOP-201 Study consists of 2 parts: Part 1 is a Lead-in Study to assess safety, PK/PD and preliminary efficacy; Part 2 is the Main Study, a Phase 2/3 randomized, double-blind, placebo-controlled trial.
Part 1 is composed of Part 1a, a Na18F positron emission tomography (PET)/computed tomography, less head (CT) Study in up to 6 participants age ≥ 15 years, and Part 1b, a flare-up Study in up to 6 participants ≥ 12 years of age. Participants enrolled in Part 1 will be randomized to one of two dose levels for 13 weeks. Participants in Part 2 will be randomized to one of two dose levels of drug vs. placebo during the 52 week trial. All participants in Part 1 or Part2 will receive study drug in the extension period of the trial.
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)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Body weight <10kg
- •Known non-healed fracture at time of Study Day
- •Planned surgery within the timeframe of the study duration or still recovering from recent surgery.
- •Respiratory compromise that requires use of supplemental oxygen.
- •Participant has
- •Known monogenic disorder other than FOP.
- •Bone or mineral disorder unrelated to FOP.
- •Malignancy (within the past 5 years, except non-melanoma skin cancer, cervical carcinoma in situ, or ductal carcinoma in situ [DCIS]).
- •Known active infection (including fungal, bacterial, mycobacterial, or viral infection including COVID19)
- •Uncontrolled hypoparathyroidism or hyperparathyroidism.
- •Per participant report or chart review (no testing required): Uncontrolled hyperthyroidism
- •Use of the following medication:
- •Systemic corticosteroids with a prednisone equivalent of >10mg/day within 1 week of Study Day
- •If the participant requires chronic use of >10mg/day prednisone equivalent of corticosteroids, eligibility will be discussed with the Sponsor.
- •NSAIDs of higher than doses recommended by the May 2022 ICCFOP guidelines within 1 week of Study Day
- •If the participant requires chronic use of NSAIDs at doses higher than those recommended by the May 2022 ICCFOP guidelines doses, eligibility will be discussed with the Sponsor.
- •Current or chronic use of tetracycline drugs (e.g., tetracycline, demeclocycline, doxycycline, or minocycline).
- •Chronic use of any of unproven therapies for FOP.
- •Palovarotene
- •Within 1 month of Study Day 1 for all participants
- •Within 2 years of Study Day 1 for female participants <8 years of age Or male participants <10 years of age
- •Treatment with another investigational product within 5 half lives of last dose at the time of Study Day 1 or 1 month, whichever is longer.
- •History of allergy or hypersensitivity to andecaliximab or its excipients.
- •Significant current laboratory abnormalities
- •Breastfeeding, pregnant, or planning pregnancy.
- •Those of childbearing potential unwilling to agree to abstain from sexual activity that could result in pregnancy or unwillingness to use acceptable birth control during the study and for 90 days after the last dose.
- •Simultaneous participation in another clinical trial involving another investigational product.
- •Significant medical condition or disability or biochemical or hematologic abnormalities that in the opinion of the Investigator would expose the participant to undue risk, prevent the conduct of study procedures, or confound the study results.
- •Note: Other protocol defined Inclusion/Exclusion Criteria apply
研究组 & 干预措施
Part 1a: PET/CT Study
a 13-week double-blind (Investigator and Participant blinded; Sponsor unblinded) Study to assess the impact of two dose levels of andecaliximab administered subcutaneously (SC), once-a-week (QW) in participants age ≥ 15 years, with FOP on a number of outcomes including Safety, Pharmacokinetic (PK) and pharmacodynamic (PD) and the change from baseline of Na18F uptake in HO lesions by PET/CT scan, and Patient Reported Outcomes (PROs).
干预措施: Andecaliximab (Drug)
Part 1b: Flare-up Study
a 13-week double-blind (Investigator and Participant blinded; Sponsor unblinded) study to assess the impact of two dose levels of andecaliximab administered SC QW in participants ≥12 years of age with a recent history of frequent flare-up episodes on a number of outcomes including safety, PK/PD, and flare-up incidence and symptoms and PROs.
干预措施: Andecaliximab (Drug)
Part 2: Main Study
1-year (52-week) double-blind (Investigator, participant, and sponsor all blinded), placebo-controlled study of andecaliximab Dose level A or B (or age adjusted) SC QW or placebo in pediatric and adult patients with FOP. The Main Study will enroll approximately 80 participants, randomized in a 1:1:1 ratio to andecaliximab Dose level A or B (or age adjusted) SC QW or placebo.
干预措施: Placebo (Drug)
Part 2: Main Study
1-year (52-week) double-blind (Investigator, participant, and sponsor all blinded), placebo-controlled study of andecaliximab Dose level A or B (or age adjusted) SC QW or placebo in pediatric and adult patients with FOP. The Main Study will enroll approximately 80 participants, randomized in a 1:1:1 ratio to andecaliximab Dose level A or B (or age adjusted) SC QW or placebo.
干预措施: Andecaliximab (Drug)
结局指标
主要结局
Number of New HO Lesions as Assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)]
时间窗: Week 27 and 53
Low dose WBCT-LH (whole body CT less head) is used to create detailed images of soft tissues and bones.
次要结局
- Percent change from baseline in Na18F standardized uptake value maximum (SUVmax) of up to 7 individual HO lesion(s) per participant active at baseline as assessed by Na18F PET/CT (Part 1a).(Week 14)
- Number of days during which a flare-up is experienced by the participant as reported by the participant(Week 14, 27 and 53)
- Number of Participants With Serious Treatment-Emergent Adverse Events (Serious TEAEs)(Week 27 and 53)
- Change in patient quality of life as assessed by the EuroQol 5 dimensions questionnaire with a 5-level scale (EQ-5D-5L)(Week 27 and 53)
- Change in HO volume over time as assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)](Week 27 and 53)
- Change in patient joint involvement as assessed by Investigator using Cumulative Analog Joint Involvement Scale (CAJIS)(Week 27 and 53)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Week 27 and 53)
- Number of Participants With TEAEs by Severity(Week 27 and 53)
- Change in HO volume over time as assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)] (Part 1a)(Week 14)
- Number of flare-ups as reported by the participant(Week 14, 27 and 53)
- Number of flare-ups as reported by the participant and confirmed by the Principal Investigator(Week 14, 27 and 53)