A Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis (ALS)

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-003349-13-BE
• Date of registration: 02/10/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: A Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis - Ozanezumab Phase II study in patients with ALS
• Date of first enrolment: 06/12/2012
• Target sample size: 294
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003349-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, United Kingdom, United States

Contacts

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:
Deviations from inclusion criteria are not allowed because they can potentially jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. Therefore,
adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the revised World Federation of Neurology El Escorial criteria [Rix Brooks, 2000].
2. Onset of muscle weakness no more than 30 months before screening visit.
3. SVC of at least 65% predicted for gender, age, ethnicity and height at Screening.
4. If on riluzole, the dose must have been stable for at least 28 days prior to Baseline visit.
5. Age 18 – 80 years inclusive.
6. Female subjects may participate if they are of non-child-bearing potential or if they are of child-bearing potential and agree to satisfy one of the requirements for contraception listed in Appendix 4 (Section 11.4) during the study and 4 months
after the last dose to avoid pregnancy. Women of childbearing potential must have a negative pregnancy test and be non-lactating.
7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin = 1.5xULN.
8. 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).
9. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 279
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
Deviations from exclusion criteria are not allowed because they can potentially jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1. 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 or could have any other effect on the study efficacy or
safety assessments that in the opinion of the investigator would impact participation in the study.
2. Patients with primary lateral sclerosis, monomelic ALS, ALS Parkinsonism dementia complex.
3. Patients requiring non-invasive or mechanical ventilation (non-invasive ventilation for sleep apnoea is allowed subject to discussion with Medical Monitor).
4. Patients on diaphragmatic pacing.
5. Presence of any of the following clinical conditions:
a. Drug abuse or alcoholism (according to Diagnostic and Statistical Manual of Mental Disorders –Fourth Edition [DSM-IV] criteria).
b. Uncontrolled hypertension despite optimal antihypertensive treatment; unstable cardiovascular, pulmonary, renal, endocrine or hematologic condition; current malignancy.
c. Active major infectious disease e.g. systemic infections with visceral involvement (pneumonia, pyelonephritis, endocarditis) and/or septicaemia.
d. Unstable psychiatric illness, such as psychosis or untreated major depression, within 90 days of the Screening visit.
6. Subjects, who in the investigator's judgement, pose a significant suicide risk.
7. 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.
8. Subjects who have participated in a clinical trial involving receipt of a biopharmaceutical product (recombinant proteins, monoclonal antibodies, blood products, sera, allergens, and gene and cell therapy products) within 6 months prior to the first dosing day.
9. Patients who have received any type of vaccination within 2 weeks prior to study drug administration.
10. Chronic (>3 months) use of systemic immunosuppressants including systemic steroids.
11. Exposure to non-biological experimental agents (including investigational products and marketed medications used off-label) 1 month or 5 half-lives prior to Baseline visit (whichever is longer).
12. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 15.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Ozanezumab
Product Code: GSK1223249
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Ozanezumab
CAS Number: 1310680-64-8
Current Sponsor code: GSK1223249
Other descriptive name: Immunoglobulin G1, anti (protein Nogo A) (human Mus musculus monoclonal heavy chain), disulfide with human Mus musculus monoclonal light chain, dimer
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: 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.

Main Objective: 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 Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R).

Timepoint(s) of evaluation of this end point: ALSFRS-R will be assessed every 4 weeks for 48 weeks. Primary endpoint evaluated at Week 48.

Primary end point(s): The primary endpoint is the joint rank scores for combined analysis of function and survival (also called joint rank analysis). Function is measured using the amyotrophic lateral sclerosis functional rating scale – revised (ALSFRS-R)

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints include: Change from Baseline in ALSFRS-R, Slow Vital Capacity (SVC), Muscle Strength (HHD), Amyotrophic lateral sclerosis assessment questionnaire-40 (ALSAQ-40), EuroQoL – Short form EQ-5D-L, ; Proportion of clinical global impression - improvement (CGI-I) responders; Overall survival and progression free survival.

Timepoint(s) of evaluation of this end point: Endpoints evaluation at Week 48 (and week 60 for overall survival). Actual assessments administered every 4 weeks or 3 months depending on assessment.

Secondary ID(s)

NOG112264

Source(s) of Monetary Support

GlaxoSmithKline