Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study (ICA-GBS)

Guillian-Barre Syndrome (GBS) is the most frequent cause of acute neuromuscular weakness in the Western World and can occur at any age. GBS is a rpadily progressive 'inflammatory' disorder of the perihperal nerves often leading to sever paresis of the limbs. Most GBS patients also have sensory disturbances (tingling or dull feeling) and pain. Some patients also have double vision or problems with swallowing. GBS mau also involve the respiratory muscles, leading to insufficient ventilation and admission to an intensive care unit. GBS pateints have a vairable prognosis; 20-30% require mechnical ventilation for a period ranging from weeks to months, 20% are unable to walk after 6 months nad 3-5% dies. Progression of weakness in GBS is usually rapid and reaches its peak within 4 weeks in the majority of patients, but many develop their maximum deficit within 2 weeks. Thereafter, the patients have a variable prognosis.

GBS is a treatable disorder. Intravenous immunoglobulin (IVIg) 2g/kg administered in 5 days was shown to be effective when administered within the first two weeks after onset of symptoms, and is considered the treatment of choice by most experts in the field. Although the standard treatment for GBS is a single course of IVIg (2g/kg administered in 5 days), many patients fails to recover abd remain with substantial disability. Patients with GBS and especially those with a poor prognosis potentially may benefit from more powerful abd when possible a more mechanistically rational therapy.

Recent experimental evidence suggests that complement activation palys a crucial role in the development of neuromuscular weakness in GBS making complement inhibitors and regulators attracive therapeutic targets. Our hypothesis is that Eculizumab, with its function as a complement inhibitor, will be very effective in preventing progression of weakness in patients with GBS.

Study Overview

• Status: Unknown
• Conditions: Gullian Barre Syndrome
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Govindsinh Chavada; Email: govindsinh.chavada@glasgow.ac.uk
• Study Contact Backup: Name: Ian Anderson; Phone Number: 0141 201 2457; Email: ian.anderson2@ggc.scot.nhs.uk

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Recruiting
    • Southern General Hospital
    • Contact: Govindsinh Chavada; Email: govindsinh.chavada@glasgow.ac.uk
    • Contact: Amy Davidson, MBChB, BSc, MRCP; Email: amy.davidson2@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged >18 years diagnosed with GBS according to NINDS diagnostic criteria
• Onset of weakness due to GBS is less than 2 weeks ago
• Patients who are unable to walk unaided for >10 metres (grade >3 on GBS disability scale)
• Patients who are being considered for or already on IVIg treatment
• First dose of eculizumab must be started within 2 weeks from onset of weakness and any time during the IVIg treatment period
• Signed informed consent

Exclusion Criteria:

• Age <18 years
• Patients who are being considered for, or already on, plasma exchange
• Pregnancy or lactation
• Patients show clear clinical evidence of a polyneuropahty caused by e.g. diabetes mellitus (except mild sensory), alcoholism, severe vitamin deficiency, and porphyria
• Patients received immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycofenolatemofetil, tacrolimus, sirolimus or > 20 mg prednisolone daily) during the last month
• Patients known to have severe concurrent disease, like malignancy, severe cardiovascular disease, AIDS, severe COPD, TB
• Inability to comply with study related procedures or appointments during 6 months
• Any condition that in the opinion of the investigator could increase the patient's risk by participating in the study or confound the outcome of the study
• Related to the administration of eculizumab:

Unresoled Neisseria meningitidisinfection of history of meningococcal infection Unsuitable for antibiotic prophylaxis (e.g due to allergy) Known hypersensitivity to eculizumab, murine proteins or to any of the excipients Known or suspected hereditary complement deficiencies Women of child-bearing potential who are unwilling to use effective contraception during treatment and for 5 months after treatment is completed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched placebo, intravenously once a week
Experimental: Eculizumab; Eculizumab, 900 mg intravenously once a week	Drug: Eculizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the incidence of AE/SAEs after treatment with eculizumab and IVIg compared to placebo controls	Primary safety endpoint	6 months
Improvement of one or more grade in functional outcome (on the 6 point GBS disability scale) at 4 weeks	Primary efficacy endpoint	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of ventilatory support		8 weeks
Ability to walk unaided (GBS disability score 2) at 8 weeks		8 weeks
Time taken to improve by at least one grade (on the GBS disability scale)		8 weeks
Time taken to walk independently		1 year
Difference in GBS disability score at maximum disability completed with 6 months		6 months
Percentage of patients with a clinically relevant improvement in R-ODS score	An increase from Baseline in R-ODS score by at least 6 points on the centile metric score at 4 weeks and 6 months	6 months
Percentage of patients with a clinically relevant improvement in ONLS	Defined as an increase from baseline in ONLS score by at least 1 point at 4 weeks and 6 months	6 months
Requirement for ventilatory support (GBS disability score 5)		4 weeks
Occurrence of relapse		2 years
Dearth within the first 6 months		6 months

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow

Publications and helpful links

General Publications

• Davidson AI, Halstead SK, Goodfellow JA, Chavada G, Mallik A, Overell J, Lunn MP, McConnachie A, van Doorn P, Willison HJ. Inhibition of complement in Guillain-Barre syndrome: the ICA-GBS study. J Peripher Nerv Syst. 2017 Mar;22(1):4-12. doi: 10.1111/jns.12194.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): October 1, 2015
• Study Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 6, 2014
• First Posted (Estimate): January 7, 2014

Study Record Updates

• Last Update Posted (Estimate): September 23, 2014
• Last Update Submitted That Met QC Criteria: September 22, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Polyneuropathies; Syndrome; Guillain-Barre Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: GN12NE462