A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF 06939926 FOR THE TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 114
- 试验地点
- 94
- 主要终点
- Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
研究概览
简要总结
The study will evaluate the safety and efficacy of gene therapy in boys with DMD. It is a randomized, double-blind, placebo-controlled study with two thirds of participants assigned to gene therapy. The one third of participants who are randomized to the placebo arm will have an opportunity for treatment with gene therapy at the beginning of the second year.
详细描述
The study will assess the efficacy of PF-06939926 gene therapy on ambulatory function while also monitoring its safety. Approximately 99 boys with DMD will be enrolled and randomly assigned to one of two groups: approximately two thirds will be in Cohort 1 and receive gene therapy at the start of the study; approximately one third will be in Cohort 2 and receive placebo at the start of the study and receive gene therapy after one year, as long as it remains safe to do so. The treatment (PF-06939926 gene therapy or placebo) will be given as an intravenous infusion lasting up to 2 hours.
The study includes boys who are at least 4 years old and less than 8 years old (including 7 year olds up until their 8th birthday). All boys will need to be on a daily dose of glucocorticoids (prednisone, prednisolone, or deflazacort) for at least 3 months prior to enrolling and to stay on daily glucocorticoids for the first 2 years of the study. All boys will need to be negative for neutralizing antibodies against AAV9, as measured by the test done for the study as part of screening.
The primary outcome of the study will be assessed at 52 weeks. All participants will be followed in the study for 15 years after treatment with gene therapy. Participants who received fordadistrogene movaparvovec in Pfizer studies C3391001 and C3391008 or are currently enrolled in Pfizer study C3391011 will be allowed to roll over into the long-term safety follow-up period of this study and will be considered Cohort 3.
The study medication, all medical tests associated with the study, and the visits to the study sites are free of charge. Participants will also be supported for travel costs associated with study visits.
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
The study will be quadruple blind.
入排标准
- 年龄范围
- 4 Years 至 7 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of Duchenne muscular dystrophy by prior genetic testing
- •Receiving a stable daily dose (at least 0.5 mg/kg/day prednisone or prednisolone, or at least 0.75 mg/kg/day deflazacort) for at least 3 months prior to Screening
- •Ambulatory, as assessed by protocol-specified criteria
排除标准
- •Positive test performed by Pfizer for neutralizing antibodies to AAV9
- •Any treatment designed to increase dystrophin expression within 6 months prior to screening (e.g., Translarna™, EXONDYS 51™, VYONDYS 53™)
- •Any prior treatment with gene therapy
- •Any non-healed injury that may impact functional testing (eg NSAA)
- •Abnormality in specified laboratory tests, including blood counts, liver and kidney function
- •Any of the following genetic abnormalities in the dystrophin gene:
- •Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR
- •A deletion that affects both exon 29 and exon 30;OR
- •A deletion that affects any exons between 56-71, inclusive.
研究组 & 干预措施
Cohort 1
Approximately two thirds of participants will be randomized to Cohort 1.
干预措施: Placebo (Other)
Cohort 1
Approximately two thirds of participants will be randomized to Cohort 1.
干预措施: PF-06939926 (Genetic)
Cohort 2
Approximately one third of participants will be randomized to Cohort 2.
干预措施: Placebo (Other)
Cohort 2
Approximately one third of participants will be randomized to Cohort 2.
干预措施: PF-06939926 (Genetic)
结局指标
主要结局
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
时间窗: Baseline, Week 52
The NSAA was a 17-item test that graded performance of various functional skills using the following scale: 0 (unable to achieve independently), 1 (modified method but achieves goal independent of physical assistance from another), and 2 ("normal"- no obvious modification of activity). Total score was calculated as the sum of all 17 individual item responses and ranged from 0 (worst) to 34 (fully independent function) with higher scores indicating better function. Baseline NSAA total score is defined as the last non-missing NSAA total score collected prior to Year 1 drug administration.
次要结局
- Change From Baseline in Percent Normal Dystrophin Expression Level in Muscle Biopsies by Liquid Chromatography Mass Spectrometry (LC-MS) Based on LLQV Peptide at Week 52(Baseline, Week 52)
- Change From Baseline in Percent of Muscle Fibers Expressing Mini-Dystrophin in Muscle Biopsies by Immunofluorescence at Week 52(Baseline, Week 52)
- Change From Baseline in Serum Creatine Kinase (CK) Concentration at Week 52(Baseline, Week 52)
- Least Square Mean of Proportion of Skills Gained Based on the Individual Items of the NSAA at Week 52(Baseline, Week 52)
- Least Square Mean of Proportion of Skills Either Improved or Maintained Based on the Individual Items of the NSAA at Week 52(Baseline, Week 52)
- Change From Baseline in 10 Meter Run/Walk Velocity at Week 52(Baseline, Week 52)
- Change From Baseline in Rise From Floor Velocity at Week 52(Baseline, Week 52)
- Change From Baseline in Modified Pediatric Outcome Data Collection Instrument (PODCI)- Transfer and Basic Mobility Core Scale at Week 52(Baseline, Week 52)
- Change From Baseline in Modified PODCI- Sports and Physical Functioning Core Scale at Week 52(Baseline, Week 52)