NCT01254019已完成3 期
A Phase III, Randomized, Double Blind, Placebo-controlled Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Change From Baseline in Muscle Function Using the 6 Minute Walking Distance (6MWD) Test Assessed at Week 48
研究概览
简要总结
The purpose of this study is to determine whether GSK2402968 is effective in the treatment of ambulant boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation/deletion within the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping.
- •Males, aged at least 5 years, and with life expectancy of at least 1 year
- •Able to complete 6MWD test with minimal distance of at least 75m at each predrug visit. In addition, results of 6MWD must be within 20% of each other at each pre-drug visit
- •Receiving glucocorticoids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly for the duration of the study
- •QTc <450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), or <480 msec for subjects with Bundle Branch Block. Note: QTc may be either QTcB or QTcF, and machine read or manual overread.
- •Subjects, where appropriate, must be willing to use adequate contraception (condoms or abstinence) for the duration of the study and for at least 5 months after the last dose of study drug.
- •Willing and able to comply with all protocol requirements and procedures,
- •Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
- •French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
排除标准
- •Any additional missing exon for DMD that cannot be treated with GSK2402968
- •Current or history of liver or renal disease or impairment
- •Acute illness within 4 weeks of the first anticipated administration of study medication which may interfere with study assessments
- •Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, within 6 months of the first administration of study medication; and idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication.
- •Current or anticipated participation in any investigational clinical studies
- •Positive hepatitis B surface antigen, hepatitis C antibody test (if verified via RIBA or PCA testing), or human immunodeficiency virus (HIV) test at screening,
- •Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at Screening, the investigator should discuss inclusion of subject in the study with the medical monitor,
- •Children in Care. The definition of a Child in Care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.
研究组 & 干预措施
GSK2402968
Experimental
6mg/kg
干预措施: GSK2402968 6mg/kg/week (Drug)
Placebo
Experimental
dose-matched
干预措施: GSK2402968 6mg/kg/week (Drug)
结局指标
主要结局
Change From Baseline in Muscle Function Using the 6 Minute Walking Distance (6MWD) Test Assessed at Week 48
时间窗: Baseline (Day 0) and Week 48
During the 6MWD, participants were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told that they may stop earlier if they feel unable to continue. The total distance walked within 6 minutes (or until the participant stopped in case of early termination of the test), the 6MWD, was recorded in meters as well as any falls. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
次要结局
- Change From Baseline in the Linearized North Star Ambulatory Assessment (NSAA) Total Score at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in the 4 Stair Climb (Ascent) Velocity at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in the 10-meter Walk/Run Velocity at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in the Timed Function Test Rise From Floor at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in the 4 Stair Climb (Descent) Velocity at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in Muscle Strength (Total Score) at Week 48(Baseline (Day 0) and Week 48)
- Kaplan-Meier Estimates for Time to Loss of Ambulation(Week 48)
- Number of Participants Who Experienced Accidental Falls During 6MWD Assessments at Week 48(Week 48)
- Change From Baseline in Creatine Kinase Serum Concentrations at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in Pulmonary Function Test Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) at Week 48(Baseline (Day 0) and Week 48)
- Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48(Week 48)
- Change From Baseline in Pediatric Quality of Life (PedsQL) Total Score at Week 48(Baseline (Day 0) and Week 48)
- Change From Baseline in Pulmonary Function Test Peak Cough Flow (PCF) and Peak Flow (PF) at Week 48(Baseline (Day 0) and Week 48)
- Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48(Week 48)
- Change From Baseline in Health Utilities Index (HUI) Scores at Week 48(Baseline (Randomization Visit, Day 0) and Week 48)
- Number of Participants With Adverse Events (AE) and Severe Adverse Events (SAE)(Up to Follow-up (Week 68))
- Number of Participants With Vital Sign Data for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) and Heart Rate (HR) of Potential Clinical Concern (PCC) at Any Visit Post-Baseline(Up to Week 48)
- Number of Participants With Abnormal-clinically Significant Electrocardiogram (ECG) Findings at Any Visit Post-Baseline(Up to Week 48)
- Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline(Up to Week 48)
- Number of Participants With Coagulation Parameters of PCC at Any Visit Post-Baseline(Up to Week 48)
- Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline(Up to Week 48)
- Number of Participants With Urinalysis Data Outside the Reference Range (>Reference Range High) at Any Visit Post- Baseline(Up to Week 48)
- Plasma Concentrations of GSK2402968 Following Subcutaneous Administration(Randomization (Week 0 at 0.5, 1 and 3 hours), Week 8 (pre-dose, 1-4 hours), Week 12 (pre-dose, 1-4 hours), Week 24 (pre-dose, 1-4 hours), Week 36 (pre-dose, 1-4 hours), Week 47 (pre-dose, 1-4 hours))
研究者
研究点 (1)
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