Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis - Full Text View

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:

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Genetic and Rare Diseases Information Center resources: Amyotrophic Lateral Sclerosis

U.S. FDA Resources

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 ]


Enrollment:	294
Study Start Date:	December 2012
Estimated Study Completion Date:	January 2015
Primary Completion Date:	November 2014 (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

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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:	January 29, 2015
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency 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: Food and Drug Administration 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 Amyotrophic lateral sclerosis ozanezumab 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 February 27, 2015