A Phase 3, Parallel-Group Treatment, Blinded, Randomized, Placebo-Controlled Study To Assess The Efficacy And Safety Of Pegtibatinase Administered Subcutaneously In Addition To Standard Of Care In Participants With Classical Homocystinuria Due To Cystathionine Beta Synthase Deficiency (HARMONY)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 57
- 主要终点
- Change from baseline in plasma tHcy levels
研究概览
简要总结
The purpose of this study is to measure efficacy and safety of pegtibatinase treatment compared with placebo in participants with classical HCU receiving standard of care. Study details include:
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Total Study duration: up to 38 weeks
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Screening:
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Initial Screening duration: up to 4 weeks
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Pre-treatment Diet Standardization Period duration: up to 6 weeks
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Blinded Treatment Duration: 24 weeks
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2-week blinded dose titration period
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22-week blinded assessment period
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Safety Follow-Up: 4 weeks after last dose (as applicable for those not enrolling in the long term extension study, ENSEMBLE)
详细描述
Overall Design:
This global Phase 3 multi-center, multi-national, randomized, blinded, placebo-controlled study will be conducted in participants with classical CBS deficient HCU receiving standard of care who continue to have tHcy levels ≥50 μM. The total study duration will be up to 38 weeks. Approximately 70 participants (35 per arm) will be randomized to receive active drug or placebo (1:1 allocation).
Screening:
Participants will enter into a 2-phase Screening period of up to 10 weeks:
- Initial Screening: up to 4-week period during which participants will be assessed for eligibility
- Pre-treatment Diet Standardization Period (DSP): After meeting initial eligibility criteria, participants will begin a pre treatment DSP of up to 6 weeks. The DSP is intended to help minimize variability in protein intake and supplements throughout the randomized portion of the study.
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
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be ≥12 to ≤65 years of age, at the time of signing the informed consent
- •Must have a diagnosis of classical HCU based on clinical, biochemical, and/or molecular genetic testing
- •Plasma tHcy ≥80 µM at Screening visit, with allowance for up to 18 participants who may be enrolled with a Screening plasma tHcy ≥50 to <80 µM
- •Participants who can become pregnant must have a negative pregnancy test before starting the study and must use a highly effective form of birth control (less than 1% risk of pregnancy per year) during the study and for at least 4 weeks after the last dose.
- •Willing to maintain a generally stable diet for the duration of the study (unless changes are required based on medical/safety reasons)
- •Willing to maintain generally stable intake and doses of betaine, pyridoxine, and medical food for the duration of the study (unless changes are required based on medical/safety reasons)
排除标准
- •Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorder of cobalamin metabolism
- •Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU).
- •History of major thrombotic event (eg, cerebrovascular accident, myocardial infarction, pulmonary embolism) in the previous 6 months.
- •Body weight ≥160 kg.
- •Use or planned use of any injectable drugs containing PEG (excluding PEG-containing vaccines)
- •Any previous exposure to pegtibatinase and/or previous participation in a clinical study that included administration of pegtibatinase or pegtarviliase
- •Prior severe immune reaction to a PEG-containing product
研究组 & 干预措施
placebo
干预措施: Placebo (Other)
pegtibatinase
干预措施: Pegtibatinase (Drug)
结局指标
主要结局
Change from baseline in plasma tHcy levels
时间窗: Weeks 6 - 12
The change from baseline in plasma tHcy levels averaged over Weeks 6 through 12 in participants receiving standard of care and treated with pegtibatinase as compared to participants receiving standard of care and placebo
次要结局
- Plasma tHcy levels(Weeks 16 - 24)