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:
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