Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 1
- 主要终点
- Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
研究概览
简要总结
This is a 48-week, randomised, multi-centre, double-blind, placebo-controlled, parallel group investigation of the efficacy and safety of intravenous (IV) ozanezumab (GSK1223249) compared to placebo in subjects with Amyotrophic Lateral Sclerosis (ALS). Following a screening period of up to four weeks, eligible subjects will be randomised (1:1) to receive IV placebo or 15 milligram (mg)/ kilogram (kg) IV ozanezumab every 2 weeks for a period of 48 weeks with a follow-up visit around 14 weeks after the last infusion. A total of approximately 294 eligible subjects will be randomised from approximately 37 centers worldwide. The primary objective is to assess the effect of ozanezumab on the physical function and survival of ALS subjects over a treatment period of 48 weeks. Function will be measured using the ALS Functional Rating Scale - Revised (ALSFRS-R). Secondary objectives include the evaluation of other clinical outcomes associated with ALS (respiratory function, muscle strength, progression free survival and overall survival) in support of the primary objective. Quality of life, safety, tolerability, immunogenicity and pharmacokinetics (ozanezumab and riluzole) will also be assessed.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with diagnosis of familial or sporadic ALS
- •Onset of muscle weakness no more than 30 months before screening visit.
- •Slow Vital Capacity (SVC) of at least 65% predicted for gender, age, ethnicity and height at Screening.
- •If on riluzole, the dose must have been stable for at least 28 days prior to Baseline visit.
- •Age 18 - 80 years inclusive.
- •Female subjects may participate if they are of non-child-bearing potential or if they are of child-bearing potential they must agree to use the approved contraceptive methods
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2x upper limit of normal (ULN); alkaline phosphatase and bilirubin <=1.5xULN.
- •QTc (both QTcB and QTcF) <450 milliseconds (msec) or <480 msec for subjects with Bundle Branch Block at Screening and Baseline (average from triplicate ECGs).
排除标准
- •Patients with other neuromuscular disorders (including a history of polio) which in the opinion of the investigator could have contributed to the muscular atrophy or weakness caused by ALS
- •Patients with primary lateral sclerosis, monomelic ALS, ALS Parkinsonism dementia complex.
- •Patients requiring non-invasive or mechanical ventilation (non-invasive ventilation for sleep apnoea is allowed subject to discussion with Medical Monitor)
- •Patients on diaphragmatic pacing.
- •Presence of any of the following clinical conditions: Drug abuse or alcoholism, uncontrolled hypertension, active major infectious disease, unstable psychiatric illness within 90 days of the Screening visit
- •Subjects, who in the investigator's judgement, pose a significant suicide risk. - Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), positive Hepatitis B surface antigen or Hepatitis C antibody test.
- •Subjects who have participated in a clinical trial involving receipt of a biopharmaceutical product within 6 months prior to the first dosing day.
- •Exposure to non-biological experimental agents 1 month or 5 half-lives prior to Baseline visit (whichever is longer).
- •History of sensitivity to ozanezumab, or components thereof, or a history of other allergies that, in the opinion of the investigator, contraindicates participation in the study.
研究组 & 干预措施
Ozanezumab IV
Administered by IV route. Treatment period - 48 Weeks
干预措施: Ozanezumab (Drug)
Placebo
Normal saline by IV route. Treatment period - 48 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
时间窗: Week 48
The joint rank score is a combined assessment of function and survival. Function is assessed using change from Baseline in the ALSFRS-R total score. To calculate joint rank scores, every participant was compared with all other participants in a pair wise manner and assigned a score of -1, 0 or 1 based on their relative outcomes. A subject's joint rank score is the sum of their scores across the pair wise comparisons. The . The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing. Lower scores of ALSFRS-R reflect greater impairment.
次要结局
- Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48(Week 48)
- Change From Baseline in Slow Vital Capacity (SVC) at Week 48(Baseline and Week 48)
- Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48(Baseline and Week 48)
- Overall Survival at Week 48 and Week 60(Week 48 and Week 60)
- Change From Baseline in the ALSFRS-R Total Score at Week 48(Baseline and Week 48)
- Change From Baseline in the EuroQol 5 Dimensions-5 Level Short Form (EQ-5D-5L) Utility Score at Week 48(Baseline and Week 48)
- Rate of Decline Over Week 48 in the ALSFRS-R Total Score(Baseline to Week 48)
- Progression-free Survival at Week 48(Week 48)
- Change From Baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48(Baseline and Week 48)