NCT02851797已完成3 期
Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
Italfarmaco42 个研究点 分布在 11 个国家目标入组 179 人开始时间: 2017年6月6日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 179
- 试验地点
- 42
- 主要终点
- Mean Change From Baseline in 4 Standard Stairs (4SC) Climb After 18 Months of Treatment
研究概览
简要总结
Primary Objective
The primary objective of the study was to establish the effects of givinostat versus placebo administered chronically over 18 months to slow disease progression in ambulant DMD subjects.
Secondary Objectives
The secondary objectives of this study were:
- To assess the safety and tolerability of givinostat versus placebo administered chronically in DMD subjects
- To evaluate the PK profile of givinostat administered chronically in DMD subjects
- To evaluate the impact on quality of life (QoL) and activities of daily living of givinostat versus placebo administered chronically.
详细描述
This was a phase 3, randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of givinostat in ambulant subjects with DMD. This study included ambulant male paediatric subjects aged ≥ 6 years at baseline affected by DMD.
A total of 179 male ambulant subjects was randomized 2:1 (givinostat: placebo).
Subjects were stratified for their concomitant use of steroids in 4 strata:
- Deflazacort daily regimen
- Deflazacort intermittent regimen
- Other steroids daily regimen
- Other steroids intermittent regimen. The study duration was planned to be 19 months.
Givinostat or placebo oral suspension (10 mg/mL) was administered orally as 2 oral doses daily while the subject were in fed state, according to the child's weight.
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
- 6 Years 至 17 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Are an ambulant male aged ≥6 years at randomisation with DMD characteristic clinical symptoms or signs (e.g., proximal muscle weakness, Gowers' maneuver, elevated serum creatinine kinase level) already present at screening;
- •Have DMD diagnosis confirmed by genetic testing;
- •Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to local regulations);
- •Are able to complete 2 Four Stairs Climb test (4SC) screening assessments; the results of these tests must be within ±1 second of each other;
- •Have the mean of 2 screening 4SC assessments ≤8 seconds;
- •Have time to rise from floor between ≥3 and <10 seconds at screening
- •Have manual muscle testing (MMT) of quadriceps at screening Grade ≥- 3;
- •Have used systemic corticosteroids for a minimum of 6 months immediately prior to the start of study treatment, with no significant change in corticosteroids type or dosage or dosing regimen (excluding changes related to body weight change) for a minimum of 6 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
- •Subjects must be willing to use adequate contraception.
排除标准
- •Have exposure to another investigational drug within 3 months prior to the start of study treatment;
- •Have exposure to idebenone within 3 months prior to the start of study treatment;
- •Have exposure to any dystrophin restoration product (e.g., Ataluren, Exon skipping) within 6 months prior to the start of study treatment;
- •Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to the start of study treatment (e.g., growth hormone); Vitamin D, calcium, and any other supplements will be allowed as long as their intake has been stable for 3 months prior to the start of study treatment; Testosterone will also be allowed if it is used as a replacement therapy for the treatment of delayed puberty, and testosterone dose and regimen have been stable for at least 6 months and circulating testosterone levels are within the normal ranges for the subject's age;
- •Have surgery that might have an effect on muscle strength or function within 3 months before study entry or planned surgery at any time during the study;
- •Loss of ≥30 degrees of plantar flexion from the normal range of movement at the ankle joint due to contracture (i.e. fixed loss of more than 10 degrees of plantar flexion from plantigrade, assuming normal range of dorsiflexion of 20 degrees;
- •Change in contracture treatment such as serial casting, contracture control devices, night splints, stretching exercises (passive, active, self) within 3 months prior to enrollment, or expected need for such intervention during the study;
- •Have presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results;
- •Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD;
- •Have platelets count at screening < Lower Limit of Normal (LLN);
- •Have symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction <50% at screening;
- •Have a current or history of liver disease or impairment;
- •Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN);
- •Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit;
- •Have a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
- •Have a baseline QTcF >450 msec, or history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome);
- •Have a psychiatric illness/social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures;
- •Have any hypersensitivity to the components of study medication;
- •Have a sorbitol intolerance or sorbitol malabsorption, or have the hereditary form of fructose intolerance.
- •Have contraindications to MRI or MRS (e.g., claustrophobia, metal implants, or seizure disorder).
- •At the discretion of the Investigator, subjects not meeting inclusion/exclusion criteria may be re-screened twice with an interval of at least 3 months between assessments.
研究组 & 干预措施
givinostat
Active Comparator
Givinostat oral suspension (10 mg/mL) twice daily
干预措施: givinostat (Drug)
placebo
Placebo Comparator
Placebo oral suspension (10 mg/mL) twice daily
干预措施: placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in 4 Standard Stairs (4SC) Climb After 18 Months of Treatment
时间窗: Baseline and 18 months
The time (in seconds) to climb 4 standard-sized stairs is a TFT that represents stair-climbing ability. The test was evaluated by qualified functional evaluators (ie, physiotherapists) who were different from the site personnel who reviewed subjects' safety results. The test was performed in a standardised manner described in a specific site manual. Baseline 4SC was the measurement taken at the randomization assessment, unless this was missing, in which case baseline was taken as the last non missing value recorded prior to or on the date of first study treatment. The shorter the time, the better the outcome.
次要结局
- Mean Change From Baseline in Time to Rise From Floor After 18 Months of Treatment(Baseline and 18 months)
- Cumulative Loss of Function on the NSAA(over 18 months)
- Mean Change From Baseline in the Six-minute Walking Test (6MWT) After 18 Months of Treatment(Baseline and 18 months)
- Mean Change From Baseline in Vastus Lateralis Muscle Fat Fraction (VL MFF) at 18 Months(Baseline and 18 months)
- Evaluation of Acceptability/Palatability of the Oral Suspension(Week 4, EOS, early withdrawal)
- Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE(Baseline through end of study, that is the end of 18° month)
- Mean Change From Baseline in Total North Star Ambulatory Assessment (NSAA) Score After 18 Months of Treatment(Baseline and 18 months)
- Mean Change From Baseline of Muscle Strength Normalized Overtime(Baseline and 18 months)
研究者
研究点 (42)
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