Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

Study Purpose:

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.

Study Status:

Not recruiting

Disease:

Amyotrophic Lateral Sclerosis

Study Type:

Interventional

Type of Intervention:

Drug

Intervention Name:

Ozanezumab, Placebo

Placebo:

Phase:

Phase 2

Study Chair(s)/Principal Investigator(s):

GSK Clinical Trials, GlaxoSmithKline

Clinicaltrials.gov ID:

NCT01753076

Neals Affiliated?

No

Coordinating Center Contact Information

United States

Full Study 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.

Study Sponsor:

GlaxoSmithKline

Participant Duration:

48 weeks

Estimated Enrollment:

304

Estimated Study Start Date:

12 / 20 / 2012

Estimated Study Completion Date:

01 / 22 / 2015

Posting Last Modified Date:

12 / 21 / 2017

Date Study Added to neals.org:

12 / 20 / 2012

Minimum Age:

18 Years

Maximum Age:

80 Years

Can participants use Riluzole?

Yes

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.

GSK Investigational Site

Boston, Massachusetts 02114
United States

GSK Investigational Site

Grand Rapids, Michigan 49503
United States

GSK Investigational Site

Syracuse, New York 13210
United States

GSK Investigational Site

Columbus, Ohio 43210
United States

GSK Investigational Site

Randwick, New South Wales 2031
Australia

GSK Investigational Site

Herston, Queensland 4029
Australia

GSK Investigational Site

Leuven 3000
Belgium

GSK Investigational Site

Calgary, Alberta T3M 1M4
Canada

GSK Investigational Site

London, Ontario N6A 5A5
Canada

GSK Investigational Site

Toronto, Ontario M4N 3M5
Canada

GSK Investigational Site

Montreal, Quebec H2L 4M1
Canada

GSK Investigational Site

Montreal, Quebec H3A 2B4
Canada

GSK Investigational Site

Lille cedex 59037
France

GSK Investigational Site

Limoges cedex 87042
France

GSK Investigational Site

Montpellier cedex 5 34295
France

GSK Investigational Site

Nice cedex 3 06202
France

GSK Investigational Site

Paris cedex 13 75651
France

GSK Investigational Site

Berlin 13353
Germany

GSK Investigational Site

Jena, Thueringen 07747
Germany

GSK Investigational Site

Hannover, Niedersachsen 30625
Germany

GSK Investigational Site

Bochum, Nordrhein-Westfalen 44789
Germany

GSK Investigational Site

Muenchen, Bayern 81675
Germany

GSK Investigational Site

Ulm, Baden-Wuerttemberg 89081
Germany

GSK Investigational Site

Torino, Piemonte 10126
Italy

GSK Investigational Site

Verona, Veneto 37134
Italy

GSK Investigational Site

Kanagawa 252-0380
Japan

GSK Investigational Site

Miyagi 980-8574
Japan

GSK Investigational Site

Osaka 560-8552
Japan

GSK Investigational Site

Seoul 110-744
Korea, Republic of

GSK Investigational Site

Seoul 133-792
Korea, Republic of

GSK Investigational Site

Seoul 136-705
Korea, Republic of

GSK Investigational Site

Utrecht 3584 CX
Netherlands

GSK Investigational Site

Preston, Lancashire PR2 9HT
United Kingdom

GSK Investigational Site

Brighton BN2 5BE
United Kingdom

GSK Investigational Site

Edgbaston, B15 2TT
United Kingdom