Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Ozanezumab; Placebo
Intervention description: Ozanezumab injection solution; Normal saline (0.9% sodium chloride) infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 304.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Amyotrophic lateral sclerosis; efficacy; ozanezumab; safety

Summary:

      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.
    

Eligibility 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.