Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01753076
First received: December 17, 2012
Last updated: October 9, 2014
Last verified: October 2014
  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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Ozanezumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To assess the effect of ozanezumab on the function and survival of ALS patients [ Time Frame: Over 48 weeks ] [ Designated as safety issue: No ]
    The effect of ozanezumab on the function and survival of ALS patients will be measured by the joint rank scores for combined analysis of function and survival measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) over 48-weeks.


Secondary Outcome Measures:
  • Change from Baseline in amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS R) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from Baseline in Slow Vital Capacity (SVC) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from Baseline in Muscle Strength as measured by Hand Held Dynamometry (HDD) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of Clinical Global Impression - Improvement Scale (CGI-I) responders at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Overall Survival (at Week 48 and Week 60) [ Time Frame: Up to Week 48 and up to Week 60 ] [ Designated as safety issue: No ]
    Defined as time from randomisation to death or censored at Week 48 / Week 60 whichever comes first

  • Progression-free Survival [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Defined as time from randomisation to progression or death or censored at Week 48 whichever comes first

  • Change from Baseline to Week 48 in EuroQol-Short form (EQ 5D-L) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from Baseline to Week 48 in amyotrophic lateral sclerosis assessment questionnaire-40 (ALSAQ 40) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events (AEs) [ Time Frame: Throughout the study (screening upto follow-up) ] [ Designated as safety issue: No ]
    Number of subjects with incidence of AEs

  • Change from Baseline in vital signs (systolic blood pressure, diastolic blood pressure and heart rate) and weight [ Time Frame: up to Week 60 ] [ Designated as safety issue: No ]
  • Change from Baseline in routine laboratory tests [ Time Frame: up to Week 60 ] [ Designated as safety issue: No ]
  • Change from Baseline in electrocardiogram (ECG) parameters [ Time Frame: up to Week 60 ] [ Designated as safety issue: No ]
  • Plasma PK parameters at steady state [ Time Frame: W0, W2 (only part A), W4, W8, W12, W24, W36, W44, W48, W60 ] [ Designated as safety issue: No ]
    Estimates of individual ozanezumab PK parameters, including AUC(0-tau)ss, Cavgss, will be listed and summarized

  • Plasma concentrations of riluzole [ Time Frame: W0, W2 (only part A), W4, W8, W12, W24, W36, W44, W48, W60 ] [ Designated as safety issue: No ]
  • To assess the immunogenicity of IV ozanezumab [ Time Frame: W0, W12, W24, W36, W48 and Follow-up (W>=60) ] [ Designated as safety issue: No ]
    Incidence of anti-ozanezumab antibodies and relationship to trough concentration in serum will be measured

  • Rate of decline over 48 weeks in amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS R) total score [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 294
Study Start Date: December 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ozanezumab IV
Administered by IV route. Treatment period - 48 Weeks
Drug: Ozanezumab
Ozanezumab injection solution
Placebo Comparator: Placebo
Normal saline by IV route. Treatment period - 48 weeks
Drug: Placebo
Normal saline (0.9% sodium chloride) infusion

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01753076

  Show 35 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01753076     History of Changes
Other Study ID Numbers: 112264
Study First Received: December 17, 2012
Last Updated: October 9, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
The Netherlands: De Centrale Commissie Mensgebonden Onderzoek
France: Agence Nationale de Sécurité du Médicament et des produits de santé
United States: Institutional Review Board
Italy: Comitato Etico per la Sperimentazione, Azienda Ospedaliera Universitaria Integrata di Verona
Canada: Health Canada
Japan: Pharmaceuticals and Medical Devices Agency
Germany: Paul-Ehrlich-Institut
South Korea: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
efficacy
ozanezumab
Amyotrophic lateral sclerosis
safety

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on October 20, 2014