Last updated: 11/07/2018 04:35:36
Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Joint rank scores for combined analysis of function (amyotrophic lateral sclerosis functional rating scale revised [ALSFRS-R] score) and 48 week overall survival
Timeframe: Week 48
Secondary outcomes:
Change from Baseline in the ALSFRS-R total score at Week 48
Timeframe: Baseline and Week 48
Rate of decline over Week 48 in the ALSFRS-R total score
Timeframe: Baseline to Week 48
Change from Baseline in slow vital capacity (SVC) at Week 48
Timeframe: Baseline and Week 48
Change from Baseline in muscle strength as measured by Hand Held Dynamometry (HHD) score at Week 48
Timeframe: Baseline and Week 48
Number of clinical global impression-improvement scale (CGI-I) responders at Week 48
Timeframe: Week 48
Overall survival at Week 48 and Week 60
Timeframe: Week 48 and Week 60
Progression-free survival at Week 48
Timeframe: Week 48
Change from Baseline in the EuroQol 5 dimensions-5 level short form (EQ-5D-5L) utility score at Week 48
Timeframe: Baseline and Week 48
Change from Baseline in the amyotrophic lateral sclerosis assessment questionnaire-40 (ALSAQ-40) total score at Week 48
Timeframe: Baseline and Week 48
Interventions:
Drug: Ozanezumab
Drug: Placebo
Enrollment:
304
Observational study model:
Not applicable
Primary completion date:
2015-22-01
Time perspective:
Not applicable
Clinical publications:
Vincent Meininger, Angela Genge, Leonard H van den Berg, Wim Robberecht, Albert Ludolph, Adriano Chio, Seung H Kim, P Nigel Leigh,Matthew C Kiernan, Jeremy M Shefner, Claude Desnuelle, Karen E Morrison, Susanne Petri, Diane Boswell, Jane Temple, Rajat Mohindra, Matt Davies, Jonathan Bullman, Paul Rees, Arseniy Lavrov, on behalf of the NOG112264 Study Group*. Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(3):208-216.
Medical condition
Amyotrophic Lateral Sclerosis
Product
ozanezumab
Collaborators
Not applicable
Study date(s)
December 2012 to January 2015
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 80 years
Accepts healthy volunteers
No
- Patients with diagnosis of familial or sporadic ALS
- Onset of muscle weakness no more than 30 months before screening visit.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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).
Exclusion criteria:
- 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.
Trial location(s)
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44789
Status
Study Complete
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Study Complete
Location
GSK Investigational Site
Syracuse, New York, United States, 13210
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Preston, Lancashire, United Kingdom, PR2 9HT
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Study Complete
Location
GSK Investigational Site
Grand Rapids, Michigan, United States, 49503
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2015-22-01
Actual study completion date
2015-22-01
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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