Multiple Doses of Anti-NOGO A in Relapsing Forms of Multiple Sclerosis

Phase 1

Terminated

• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Interventions: Other: Saline placebo; Drug: GSK1223249

• Registration Number: NCT01435993
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This study will investigate an experimental new drug, GSK1223249 in patients diagnosed with relapsing forms of multiple sclerosis. The study will specifically investigate safety (vital signs like heart rate, blood pressure, Magnetic Resonance Imaging (MRI), and other markers of health from blood samples), tolerability (any side effects that occur, if any), and pharmacokinetics (how the body processes the drug and how long the drug stays in the blood, and in cerebro-spinal fluid). The study will also investigate if patients' own immune system interacts with GSK1223249.

Detailed Description

This study will be a randomised, placebo-controlled, single-blind (Investigator and Subject), single and repeat ascending dose protocol, in multiple sclerosis patients. The study is designed to evaluate the safety, tolerability, pharmacokinetics, and any potential for immunogenicity of GSK1223249 (a monoclonal antibody raised against Nogo-A), given intravenously in Multiple Sclerosis patients. The study will also evaluate exploratory endpoints including para-clinical activity via magnetic resonance imaging, cerebrospinal fluid pharmacokinetics, and effect of repeat dose administration of GSK1223249 on disability. Furthermore MS symptoms, such as relapses and individual symptom severity will be closely monitored.

Study Timeline

• Study First Submitted: 2011-08-25
• Study Start: 2011-09-08
• Study First Submitted QC: 2011-09-15
• Study First Posted: 2011-09-19
• Primary Completion: 2012-01-23
• Study Completion: 2012-01-23
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-20
• Last Update Posted: 2020-11-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• Diagnosed with a relapsing form of MS .

• Using one of the following ongoing MS treatment strategies, defined as

  1. Currently receiving Beta-interferon/Copaxone for treatment of MS and have been receiving the current course of therapy for 3 or more months prior to screening, OR
  2. Not currently receiving disease modifying therapies for treatment of MS, and has not received such therapies for at least 3 months prior to screening.

• Demonstrated clinical activity in 2 years prior to screening, whilst receiving current/previous treatment regimen or prior to any treatment regimen

• Expanded Disability Status Scale (EDSS) score ≤6.0 at either the screening or baseline visit.

• Male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent.

• Body weight equal to or greater than: 50 kilogrammes

Exclusion Criteria

• Complications/History of other diseases that may impact on safety of patients enroling into the study.
• Liver function test outside normal range for patient population
• Treatment with methylprednisolone or any other systemic steroid, for a relapse or otherwise, within 30 days of screening
• Treatment in the past 6 months with any of the following agents: Fingolimod (Gilenya), methotrexate, mitoxantrone, azathioprine, or other small molecule immunosuppressants.
• History of anaphilaxis to protein based therapeutics or mono-clonal antibodies.
• Positive result for Hapatitis B, HIV, and/or drugs of abuse, or excessive alcohol consumption.
• Not able to undergo MRI scanning safely, or Gadolinium (contrast enhancing agents) during MRI.
• Other significant infections e.g. Tuberculosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Saline placebo	Saline slow (60 minutes) intravenous infusion
Active	GSK1223249	GSK1223249 slow (60 minutes) intravenous infusion

Primary Outcome Measures

Name	Time	Method
Safety	every 2-4 weeks over 7 months	• Changes in vital signs, ECG monitoring, blood chemistry, haematology, urinalysis, monitoring of AEs and MS relapses (number, incidence, severity)

Secondary Outcome Measures

Name	Time	Method
Cmax values and AUC(0-∞)	Pre-dose; 1hr; 6hr; 12hr; 48hr; Day7; Day13; Follow-up	Profile of Pharamcokinetics
Pharmacokinetics of GSK1223249 in cerebro-spinal fluid (CSF) in MS patients	Day7; or Day 29; or Day 35; or Day 85	Measurement of GSK1223249 in CSF
Immunogenicity of GSK1223249 in MS patients	Predose; Day 85; Day169; Day197	• Presence of antibodies to GSK1223249 to be assessed in serum samples using validated ECL assays.

Trial Locations

Locations (1)

GSK Investigational Site; 🇳🇴 Lørenskog, Norway