Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

NCT ID: NCT01753076

Last Updated: 2017-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-20
• Study Completion Date: 2015-01-22

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis; efficacy; ozanezumab; safety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ozanezumab IV

Administered by IV route. Treatment period - 48 Weeks

Group Type: EXPERIMENTAL

Ozanezumab

Intervention Type: DRUG

Ozanezumab injection solution

Placebo

Normal saline by IV route. Treatment period - 48 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline (0.9% sodium chloride) infusion

Interventions

Ozanezumab

Ozanezumab injection solution

Intervention Type: DRUG

Placebo

Normal saline (0.9% sodium chloride) infusion

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Grand Rapids, Michigan, United States

GSK Investigational Site

Syracuse, New York, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Randwick, New South Wales, Australia

GSK Investigational Site

Herston, Queensland, Australia

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Lille, , France

GSK Investigational Site

Limoges, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Nice, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Bochum, North Rhine-Westphalia, Germany

GSK Investigational Site

Jena, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Turin, Piedmont, Italy

GSK Investigational Site

Verona, Veneto, Italy

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Utrecht, , Netherlands

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Preston, Lancashire, United Kingdom

GSK Investigational Site

Brighton, , United Kingdom

GSK Investigational Site

Edgbaston, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; Japan; Netherlands; South Korea; United Kingdom

References

Meininger V, Genge A, van den Berg LH, Robberecht W, Ludolph A, Chio A, Kim SH, Leigh PN, Kiernan MC, Shefner JM, Desnuelle C, Morrison KE, Petri S, Boswell D, Temple J, Mohindra R, Davies M, Bullman J, Rees P, Lavrov A; NOG112264 Study Group. Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2017 Mar;16(3):208-216. doi: 10.1016/S1474-4422(16)30399-4. Epub 2017 Jan 28.

Reference Type: DERIVED

PMID: 28139349 (View on PubMed)

Other Identifiers

112264

Identifier Type: -

Identifier Source: org_study_id