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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: November 13, 2014
Last verified: November 2014

December 17, 2012
November 13, 2014
December 2012
May 2015   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01753076 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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
Not Provided
Not Provided
 
Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Amyotrophic Lateral Sclerosis
  • Drug: Ozanezumab
    Ozanezumab injection solution
  • Drug: Placebo
    Normal saline (0.9% sodium chloride) infusion
  • Experimental: Ozanezumab IV
    Administered by IV route. Treatment period - 48 Weeks
    Intervention: Drug: Ozanezumab
  • Placebo Comparator: Placebo
    Normal saline by IV route. Treatment period - 48 weeks
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
294
May 2015
May 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Canada,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   United Kingdom
 
NCT01753076
112264
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP