Clinical trial NCT01753076: Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Official title: Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic lateral sclerosis
efficacy
ozanezumab
safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-12-20
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
timeFrame: Week 48
Secondary outcomes:
measure: Change From Baseline in the ALSFRS-R Total Score at Week 48
timeFrame: Baseline and Week 48
measure: Rate of Decline Over Week 48 in the ALSFRS-R Total Score
timeFrame: Baseline to Week 48
measure: Change From Baseline in Slow Vital Capacity (SVC) at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48
timeFrame: Baseline and Week 48
measure: Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48
timeFrame: Week 48
measure: Overall Survival at Week 48 and Week 60
timeFrame: Week 48 and Week 60
measure: Progression-free Survival at Week 48
timeFrame: Week 48
measure: Change From Baseline in the EuroQol 5 Dimensions-5 Level Short Form (EQ-5D-5L) Utility Score at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48
timeFrame: Baseline and Week 48
Other outcomes:
Locations:
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: GSK Investigational Site
state: Michigan
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Lille cedex
country: France
facility: GSK Investigational Site
city: Limoges cedex
country: France
facility: GSK Investigational Site
city: Montpellier cedex 5
country: France
facility: GSK Investigational Site
city: Nice cedex 3
country: France
facility: GSK Investigational Site
city: Paris cedex 13
country: France
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Verona
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Preston
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
city: Edgbaston,
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.