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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01753076




Registration number
NCT01753076
Ethics application status
Date submitted
17/12/2012
Date registered
20/12/2012
Date last updated
21/12/2017

Titles & IDs
Public title
Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Scientific title
Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Secondary ID [1] 0 0
112264
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ozanezumab
Treatment: Drugs - Placebo

Experimental: Ozanezumab IV - Administered by IV route. Treatment period - 48 Weeks

Placebo comparator: Placebo - Normal saline by IV route. Treatment period - 48 weeks


Treatment: Drugs: Ozanezumab
Ozanezumab injection solution

Treatment: Drugs: Placebo
Normal saline (0.9% sodium chloride) infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Change From Baseline in the ALSFRS-R Total Score at Week 48
Timepoint [1] 0 0
Baseline and Week 48
Secondary outcome [2] 0 0
Rate of Decline Over Week 48 in the ALSFRS-R Total Score
Timepoint [2] 0 0
Baseline to Week 48
Secondary outcome [3] 0 0
Change From Baseline in Slow Vital Capacity (SVC) at Week 48
Timepoint [3] 0 0
Baseline and Week 48
Secondary outcome [4] 0 0
Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48
Timepoint [4] 0 0
Baseline and Week 48
Secondary outcome [5] 0 0
Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48
Timepoint [5] 0 0
Week 48
Secondary outcome [6] 0 0
Overall Survival at Week 48 and Week 60
Timepoint [6] 0 0
Week 48 and Week 60
Secondary outcome [7] 0 0
Progression-free Survival at Week 48
Timepoint [7] 0 0
Week 48
Secondary outcome [8] 0 0
Change From Baseline in the EuroQol 5 Dimensions-5 Level Short Form (EQ-5D-5L) Utility Score at Week 48
Timepoint [8] 0 0
Baseline and Week 48
Secondary outcome [9] 0 0
Change From Baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48
Timepoint [9] 0 0
Baseline and Week 48

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/01/2015
Sample size
Target
Accrual to date
Final
304
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Herston
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
France
State/province [9] 0 0
Lille cedex
Country [10] 0 0
France
State/province [10] 0 0
Limoges cedex
Country [11] 0 0
France
State/province [11] 0 0
Montpellier cedex 5
Country [12] 0 0
France
State/province [12] 0 0
Nice cedex 3
Country [13] 0 0
France
State/province [13] 0 0
Paris cedex 13
Country [14] 0 0
Germany
State/province [14] 0 0
Baden-Wuerttemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Bayern
Country [16] 0 0
Germany
State/province [16] 0 0
Niedersachsen
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Thueringen
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Italy
State/province [20] 0 0
Piemonte
Country [21] 0 0
Italy
State/province [21] 0 0
Veneto
Country [22] 0 0
Japan
State/province [22] 0 0
Kanagawa
Country [23] 0 0
Japan
State/province [23] 0 0
Miyagi
Country [24] 0 0
Japan
State/province [24] 0 0
Osaka
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Netherlands
State/province [26] 0 0
Utrecht
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Lancashire
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Brighton
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Edgbaston,

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT01753076
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01753076