NCT01753076

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
304

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2012

Geographic Reach
11 countries

35 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 17, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 20, 2012

Completed
Same day until next milestone

Study Start

First participant enrolled

December 20, 2012

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 22, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 22, 2015

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

April 19, 2017

Completed
Last Updated

December 21, 2017

Status Verified

November 1, 2017

Enrollment Period

2.1 years

First QC Date

December 17, 2012

Results QC Date

December 1, 2016

Last Update Submit

November 27, 2017

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosisefficacyozanezumabsafety

Outcome Measures

Primary Outcomes (1)

  • Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival

    The joint rank score is a combined assessment of function and survival. Function is assessed using change from Baseline in the ALSFRS-R total score. To calculate joint rank scores, every participant was compared with all other participants in a pair wise manner and assigned a score of -1, 0 or 1 based on their relative outcomes. A subject's joint rank score is the sum of their scores across the pair wise comparisons. The . The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing. Lower scores of ALSFRS-R reflect greater impairment.

    Week 48

Secondary Outcomes (9)

  • Change From Baseline in the ALSFRS-R Total Score at Week 48

    Baseline and Week 48

  • Rate of Decline Over Week 48 in the ALSFRS-R Total Score

    Baseline to Week 48

  • Change From Baseline in Slow Vital Capacity (SVC) at Week 48

    Baseline and Week 48

  • Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48

    Baseline and Week 48

  • Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48

    Week 48

  • +4 more secondary outcomes

Study Arms (2)

Ozanezumab IV

EXPERIMENTAL

Administered by IV route. Treatment period - 48 Weeks

Drug: Ozanezumab

Placebo

PLACEBO COMPARATOR

Normal saline by IV route. Treatment period - 48 weeks

Drug: Placebo

Interventions

OzanezumabDRUG

Ozanezumab injection solution

Ozanezumab IV
PlaceboDRUG

Normal saline (0.9% sodium chloride) infusion

Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Grand Rapids, Michigan, 49503, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Herston, Queensland, 4029, Australia

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Calgary, Alberta, T3M 1M4, Canada

Location

GSK Investigational Site

London, Ontario, N6A 5A5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4M1, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3A 2B4, Canada

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Limoges, 87042, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nice, 06202, France

Location

GSK Investigational Site

Paris, 75651, France

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44789, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07747, Germany

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Turin, Piedmont, 10126, Italy

Location

GSK Investigational Site

Verona, Veneto, 37134, Italy

Location

GSK Investigational Site

Kanagawa, 252-0380, Japan

Location

GSK Investigational Site

Miyagi, 980-8574, Japan

Location

GSK Investigational Site

Osaka, 560-8552, Japan

Location

GSK Investigational Site

Utrecht, 3584 CX, Netherlands

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 133-792, South Korea

Location

GSK Investigational Site

Seoul, 136-705, South Korea

Location

GSK Investigational Site

Preston, Lancashire, PR2 9HT, United Kingdom

Location

GSK Investigational Site

Brighton, BN2 5BE, United Kingdom

Location

GSK Investigational Site

Edgbaston, B15 2TT, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 28139349DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ozanezumab

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline
866-435-7343

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 17, 2012

First Posted

December 20, 2012

Study Start

December 20, 2012

Primary Completion

January 22, 2015

Study Completion

January 22, 2015

Last Updated

December 21, 2017

Results First Posted

April 19, 2017

Record last verified: 2017-11

Locations

FR(5)US(4)GB(3)AU(2)DE(6)KR(3)NL(1)BE(1)IT(2)JP(3)CA(5)