A 2-Part, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping With an Initial Multiple Ascending Dose Part A to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ENTR-601-45, Followed by Part B to Evaluate the Safety and Efficacy of ENTR-601-45 (ELEVATE-45)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 15
- 主要终点
- Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A and OL Period).
研究概览
简要总结
This is a study of the investigational medicine ENTR-601-45 in participants who have Duchenne muscular dystrophy (DMD), a rare genetic condition. The researchers want to: Test how safe ENTR-601-45 is, learn about any side effects, and look at the potential positive effects of ENTR-601-45, compared to placebo. Placebo looks like the investigational medicine but does not contain any active ingredient. In this summary ENTR-601-45 and placebo are both called study treatments.
The study has 2 parts: Part A: to evaluate if ENTR-601-45 is safe and to determine the best dose of ENTR-601-45 for Part B. Part B: to further evaluate the effect and safety of ENTR-601-45 at the dose determined in Part A. Participants will be able to roll into an open-label treatment period during which the safety and efficacy of extended dosing will be evaluated.
Participants will:
- Receive study treatment in the form of multiple intravenous (IV) infusions (slow injection) into a vein over the course of several weeks in Part A and in Part B
- Visit the clinic regularly for checkups and tests such as: blood and urine tests, physical examinations, questionnaires, muscle biopsies and exercise tests. Participants will have a muscle biopsy at the beginning of their participation and after their last dose to allow researchers to compare whether there have been changes in the muscle as a result of the study drug.
Participants are allowed to continue receiving their standard of care therapy for DMD during the study, as long as their health remains stable.
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
- 4 Years 至 20 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Genetic diagnosis of DMD and confirmed pathologic variant in the dystrophin gene amenable to exon 45 skipping as reviewed by a central genetic counselor.
- •Assigned male at birth with clinical signs compatible with Duchenne muscular dystrophy as determined by the investigator.
- •Part A: 4-20 years of age, inclusive.
- •Ambulatory Status Part A: ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) Entry as per protocol at Screening.
- •Adequate muscle for obtaining tissue biopsy as assessed by the investigator.
- •Other protocol-defined criteria apply.
排除标准
- •Any significant concomitant medical condition that might interfere with the ability to comply with protocol requirements.
- •Has an acute illness within 4 weeks prior to the first dose of study drug which may interfere with study measurements or jeopardize participant's safety.
- •Use of the following medications :
- •Prior or current treatment with any exon skipping therapy within the previous 12 months
- •Prior or current treatment with any gene therapy
- •Use of anti-coagulants, anti-thrombotics, or anti-platelet agents from 30 days prior to screening and until the end of the study
- •Use of an immunosuppressant (other than systemic or oral corticosteroid for DMD condition) from 30 days prior to screening until the end of the study.
- •Treatment with a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat from 30 days prior to screening until the end of the study
- •Laboratory abnormalities.
- •Daytime ventilator dependence or any use of invasive mechanical ventilation via tracheostomy.
- •Has an abnormal electrocardiogram (ECG) reading assessed as clinically significant by the investigator, and/or a QT interval with Fridericia correction method (QTcF) >450 msec at Screening or prior to the first dose of study drug on Day
- •Received any experimental or investigational drug, etc. within 3 months prior to first dose or within 5 half-lives (whichever is longer).
- •Other protocol-defined criteria apply.
研究组 & 干预措施
ENTR-601-45
intravenous infusion every 6 weeks
干预措施: ENTR-601-45 (Drug)
Placebo
intravenous infusion every 6 weeks
干预措施: ENTR-601-45 - matching placebo (Drug)
结局指标
主要结局
Number of participants with Treatment Emergent Adverse Events (TEAEs) according to study protocol (Part A and OL Period).
时间窗: From baseline through End of Study (up to 62 weeks).
Safety will be assessed by monitoring adverse events, physical examination, vital signs and clinical laboratory tests.
次要结局
- Change from baseline to End of OL Period in Timed Rise from Floor (Part A and OL Period).(Baseline, End of Study (up to 62 weeks))
- Change from baseline to End of OL Period in Timed 4-Stair Climb (4SC) (Part A and OL Period).(Baseline, End of Study (up to 62 weeks))
- Change from baseline to End of OL Period in 95th centile Stride Velocity (SV95C) (Part A and OL Period).(Baseline, End of Study (up to 62 weeks))
- Change from baseline to End of OL Period in North Star Ambulatory Assessment (NSAA) (Part A and OL Period)(Baseline, End of Study (up to 62 weeks))
- Change from baseline to End of OL Period in Performance of the Upper Limb v2.0 (PUL 2.0) (Part A and OL Period).(Baseline, End of Study (up to 62 weeks))
- Percent change from baseline to end of Part A in exon 45 skipping measured in muscle biopsy (Part A)(Baseline, End of Study (Up to 25 weeks))
- Anti-drug antibody (ADA) and anti-dystrophin antibody in serum (Part A and OL Period)(From baseline through End of Study (Up to 62 weeks).)
- Change from baseline to End of OL Period in 10-Meter Walk/Run (10MWR) (Part A and OL Period).(Baseline, End of Study (up to 62 weeks))
- Plasma, muscle, and urine concentration of ENTR-601-45 and its final metabolite (Part A and OL Period)(From baseline through End of Study (Up to 62 weeks).)
- Change from baseline to End of Part A in dystrophin by Western blot from muscle biopsy (Part A).(Baseline, End of Study (Up to 25 weeks))
- Change from baseline to End of Part A in dystrophin expression and localization from muscle biopsy (Part A).(Baseline, End of Study (Up to 25 weeks))