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

A Randomized, Single Blind, Placebo-controlled, Single Ascending Dose/Repeat Dose Cohort Study to Assess Safety, Tolerability, Pharmacokinetics and Immunogenicity of GSK1223249 in Patients With Relapsing Forms of Multiple Sclerosis.

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: GSK1223249; Other: Saline placebo

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Veneto
    • Verona, Veneto, Italy, 37134
      • GSK Investigational Site
• Norway
  • Lørenskog, Norway, 1478
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; GSK1223249 slow (60 minutes) intravenous infusion	Drug: GSK1223249; Intravenous infusion
Placebo Comparator: Placebo; Saline slow (60 minutes) intravenous infusion	Other: Saline placebo; placebo intravenous infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2011
• Primary Completion (Actual): January 23, 2012
• Study Completion (Actual): January 23, 2012

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: September 15, 2011
• First Posted (Estimate): September 19, 2011

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Multiple Sclerosis, Secondary-Progressive with relapses
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: 114840; 2010-022664-12 (EudraCT Number)