NOGO-A in Multiple Sclerosis FTIH

Study Overview
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Brief Summary
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The drug being tested in this study is GSK1223249. The drug works by inhibiting a protein that prevents nerve growth. The trial is expected to involve approximately 36 patients. The study objective is to investigate the tolerability, safety and the way the body handles GSK1223249 after a range of single doses in patients with Multiple Sclerosis (MS).

Detailed Description
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This is a phase I study of GSK1223249. The study design is randomized, placebo-controlled, double-blind, sequential dose escalation, single dose administration. Approximately 36 patients with relapsing forms of Multiple Sclerosis (having had at least two relapses over the previous 24 months, OR at least one relapse within the last 12 months, OR having had at least one documented gadolinium-enhancing lesion on brain magnetic resonance imaging (MRI) within 12 months prior to Screening) will be enrolled.

Official Title
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A Randomized, Single-blind (Investigator and Subject), Placebo-controlled, Single Ascending Dose Study Exploring the Preliminary Safety, Tolerability, and Pharmacokinetics of GSK1223249 Administered by Intravenous (IV) Infusion to Subjects With Relapsing Forms of Multiple Sclerosis, Not on Disease Modifying Therapy

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Placebo
* Drug: GSK1223249


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suitable as determined by the Principal Investigator, based on his/her overall evaluation. A patient with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Diagnosed with a relapsing form of MS defined as either Relapsing Remitting MS according to revised McDonald Criteria [McDonald, 2001; Polman, 2005] plus any one of the following: Occurrence of at least one relapse in the previous 12 months OR at least 2 relapses in the previous 24 months OR at least one documented Gd-enhancing lesion by magnetic resonance imaging (MRI) within 12 months prior to screening. OR -Secondary Progressive MS, plus any one of the following: Occurrence of at least one relapse in the previous 12 months OR at least 2 relapses in the previous 24 months OR at least one documented Gd-enhancing lesion by magnetic resonance imaging (MRI) within 12 months prior to screening. Expanded Disability Status Scale (EDSS) score ≤5.5 Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent. Exclusion Criteria: Abnormal baseline blood tests Treatment with interferon-beta-1b (Betaferon), interferon-beta-1a (Rebif or Avonex), or glatiramer acetate (Copaxone) within 90 days of dosing. Treatment with methylprednisolone or any other systemic steroids within 60 days of dosing. Treatment within the past 12 months or currently with any of the following agents: cyclosporine, azathioprine, methotrexate, cladribine, natalizumab (Tysabri®) or other monoclonal antibodies, murine protein, T-cell vaccination, plasmapheresis, IVI gG, ,stem cell transplantation. History of intolerance to acetominophen, ibuprofen, naproxen or any other non-steroidal anti-inflammatory agent which would preclude use of at least one of these during the study. Previous history of anaphylaxis, severe allergic reaction, or hypersensitivity to albumin or a protein-based therapeutic, including natalizumab (Tysabri) or any other monoclonal antibody. History of hypersensitivity to any of the components of the formulation. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result. Patients with evidence of dementia or psychiatric illness which, in the Investigator's opinion, is likely to prevent them from a full understanding of and/or compliance with the study requirements and procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving GSK1223249 in cohort 1<br>Eligible subjects will receive intravenous infusion of GSK1223249 with a starting dose of 0.02 milligrams per kilograms, followed by 0.2, 2, 10 and 30 milligrams per kilograms, administered by a programmable syringe pump. | Drug: GSK1223249<br>* I.V. Infusion<br>|
| Placebo Comparator: Subjects receiving placebo in cohort 1<br>Eligible subjects will receive intravenous infusion of placebo, administered by a programmable syringe pump. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Subjects receiving GSK1223249 in cohort 2<br>Eligible subjects will receive intravenous infusion of GSK1223249 with a dose of 0.2 milligrams per kilograms administered by a programmable syringe pump. | Drug: GSK1223249<br>* I.V. Infusion<br>|
| Placebo Comparator: Subjects receiving placebo in cohort 2<br>Eligible subjects will receive intravenous infusion of placebo, administered by a programmable syringe pump. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Subjects receiving GSK1223249 in cohort 3<br>Eligible subjects will receive intravenous infusion of GSK1223249 with a dose of 2 milligrams per kilograms administered by a programmable syringe pump. | Drug: GSK1223249<br>* I.V. Infusion<br>|
| Placebo Comparator: Subjects receiving placebo in cohort 3<br>Eligible subjects will receive intravenous infusion of placebo, administered by a programmable syringe pump. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Subjects receiving GSK1223249 in cohort 4<br>Eligible subjects will receive intravenous infusion of GSK1223249 with a dose of 10 milligrams per kilograms administered by a programmable syringe pump. | Drug: GSK1223249<br>* I.V. Infusion<br>|
| Placebo Comparator: Subjects receiving placebo in cohort 4<br>Eligible subjects will receive intravenous infusion of placebo, administered by a programmable syringe pump. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Subjects receiving GSK1223249 in cohort 5<br>Eligible subjects will receive intravenous infusion of GSK1223249 with a dose of 30 milligrams per kilograms administered by a programmable syringe pump. | Drug: GSK1223249<br>* I.V. Infusion<br>|
| Placebo Comparator: Subjects receiving placebo in cohort 5<br>Eligible subjects will receive intravenous infusion of placebo, administered by a programmable syringe pump. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The preliminary safety and tolerability of single doses of GSK1223249 | changes in Vital signs, Electocardiogram, safety laboratory samples, adverse event (AE), neurological examination and MS relapses | screening, baseline (pre-dose) and up to 84 days post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single dose pharmacokinetics. | (AUC(0-∞) | screening, baseline (pre-dose) and up to 84 days post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, GSK1223249, Pharmacokinetics, Single dose escalation, anti-GSK1223249 antibodies, Multiple Sclerosis