NCT07673809招募中1 期
Multicenter, Single-blind, Randomized, Placebo-controlled Study of a Single Intravenous Infusion of a Gene Therapy Product GNR-097 in Pediatric Patients With Duchenne Muscular Dystrophy
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AO GENERIUM
- 入组人数
- 32
- 试验地点
- 6
- 主要终点
- Number and percentage of participants with treatment-emergent adverse events (AEs), AEs of special interest and serious adverse events (SAEs)
研究概览
简要总结
The study will evaluate the tolerability, safety and efficacy of gene therapy product in boys with Duchenne muscular dystrophy (DMD). In Phase I the participants will be included in two sequential dose cohorts with increasing doses of the investigational product. Based on the results of Phase I, the dose of the investigational product for use in Phase II will be determined. Phase II is a randomized, single-blind, placebo-controlled study. The participants who are randomized to the placebo arm will have an opportunity for treatment with gene therapy at the beginning of the second year.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 9 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent for participation in the trial.
- •Ambulatory boys aged 4-9 years with a documented diagnosis of DMD and clinical manifestations of the disease.
- •A frameshift mutation or nonsense mutation in the DMD gene.
- •Сreatine phosphokinase level >5000 U/L.
- •Binding antibody titer to AAV9 ≤1:50 [method: ELISA].
- •The patient is able to interact with the study physician and perform tests to assess functional activity.
- •Results of functional activity assessment tests at screening (at least in one of the two attempts performed on different days):
- •NSAA ≥22;
- •time to rise from a supine position without using surrounding objects or furniture <5 sec;
- •6MWT distance ≥350 m.
- •The patient received oral glucocorticosteroids at a stable dose for ≥12 weeks prior to signing the Informed Consent Form, and it is planned that glucocorticosteroids will be continued during the screening stage and after the patient's inclusion in the study.
- •For patients receiving deflazacort at study entry: switching the patient from deflazacort to prednisolone, in the opinion of the investigator, will not result in a significant deterioration in the patient's health.
- •The patient has been immunized with a vaccine against meningococcal serotypes A, C, Y, W135 (and B, if available) no later than 4 weeks prior to administration of GNR-097/placebo, and the immunization period expires no more than three months after the expected date of administration of GNR-097/placebo.
排除标准
- •Hypersensitivity to any component of GNR-097 or placebo.
- •Patient with cognitive impairment or a sedentary lifestyle that, in the opinion of the investigator, may interfere with the development or manifestation of motor activity.
- •Mutations in exons 8 and/or 9 of the DMD gene; for patients planned for inclusion in Cohort A, additionally: mutations in exons 1-17 and/or 59-71 of the DMD gene.
- •Clinical signs of cardiomyopathy, including left ventricular ejection fraction (Simpson) <40% based on echocardiography performed during screening.
- •Contraindications to magnetic resonance imaging.
- •History of any autoimmune disease, with the exception of drug-compensated autoimmune thyroiditis.
- •History of tuberculosis; positive or indeterminate result of Diaskintest® TigraTest® or T-SPOT.TB screening.
- •Positive results of tests for hepatitis B, hepatitis C, or HIV screening.
- •Acute infectious diseases that resolved less than 4 weeks before administration of GNR-097/placebo.
- •Immunization with a live attenuated vaccine less than 3 months before administration of GNR-097/placebo OR immunization with any inactivated vaccine less than 4 weeks before administration of GNR-097/placebo.
- •Abnormal laboratory parameters:
- •GGT level is more than three upper limits of normal;
- •total bilirubin >50.0 μmol/L (except for patients with a confirmed diagnosis of Gilbert's syndrome);
- •creatinine >160.0 μmol/L;
- •hemoglobin <80 or >180 g/L;
- •white blood cell count >18,500/μL;
- •platelet count below the lower limit of normal.
- •History of taking antisense oligonucleotides, ataluren, gene therapy using vector constructs, or cell therapy.
- •Use of immunosuppressive drugs other than glucocorticosteroids less than 12 weeks prior to signing the Informed Consent Form.
- •Participation in clinical trials less than 6 months prior to signing the Informed Consent Form.
- •Unwillingness or inability of the patient and/or their parent/legal guardian to comply with the protocol requirements and/or the trial procedures.
- •Other diseases or conditions not listed above that, in the opinion of the physician investigator and/or the Sponsor, prevent the patient from participating in the trial, including for safety reasons.
研究组 & 干预措施
Placebo followed by GNR-097
Placebo Comparator
In Phase II participants will receive matching placebo IV infusion on Day 1. Then, they will have the opportunity to receive a single IV infusion of GNR-097 at the beginning of the second year.
干预措施: Placebo followed by GNR-097 (Genetic)
GNR-097
Experimental
Participants will receive single intravenous (IV) infusion of GNR-097 on Day 1.
干预措施: GNR-097 (Genetic)
结局指标
主要结局
Number and percentage of participants with treatment-emergent adverse events (AEs), AEs of special interest and serious adverse events (SAEs)
时间窗: Baseline to End of Study (Week 104)
AEs of special interest include immune-mediated myositis, myocarditis, thrombotic microangiopathy and hemolytic uremic syndrome
次要结局
未报告次要终点
研究者
研究点 (6)
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