Study NOG112264, a Phase II Study of Ozanezumab

INTERVENTION: Product Name: Ozanezumab Product Code: GSK1223249 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: Ozanezumab CAS Number: 1310680‐64‐8 Current Sponsor code: GSK1223249 Other descriptive name: Immunoglobulin G1, anti (protein Nogo A) (human Mus musculus monoclonal heavy chain), disulfide with human Mus musculus monoclonal light chain, dimer Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Amyotrophic Lateral Sclerosis (ALS) ; MedDRA version: 14.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: 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 Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS‐R). Primary end point(s): The primary endpoint is the joint rank scores for combined analysis of function and survival (also called joint rank analysis). Function is measured using the amyotrophic lateral sclerosis functional rating scale – revised (ALSFRS‐R); ; Secondary Objective: 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. Timepoint(s) of evaluation of this end point: ALSFRS‐R will be assessed every 4 weeks for 48 weeks. Primary endpoint evaluated at Week 48. SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints include: Change from Baseline in ALSFRS‐R, Slow Vital Capacity (SVC), Muscle Strength (HHD), Amyotrophic lateral sclerosis assessment questionnaire‐40 (ALSAQ‐40), EuroQoL – Short form EQ‐5D‐L, ; Proportion of clinical global impression ‐ improvement (CGI‐I) responders; Overall survival and progression free survival. Timepoint(s) of evaluation of this end point: Endpoints evaluation at Week 48 (and week 60 for overall survival). Actual assessments administered every 4 weeks or 3 months depending on assessment. INCLUSION CRITERIA: Deviations from inclusion criteria are not allowed because they can potentially jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory‐supported probable, probable, or definite criteria for a diagnosis of ALS according to the revised World Federation of Neurology El Escorial criteria [Rix Brooks, 2000]. 2. Onset of muscle weakness no more than 30 months before screening visit. 3. SVC of at least 65% predicted for gender, age, ethnicity and height at Screening. 4. If on riluzole, the dose must have been stable for at least 28 days prior to Baseline visit. 5. Age 18 – 80 years inclusive. 6. Female subjects may participate if they are