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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by NHS Greater Glasgow and Clyde
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:
NCT02029378
First received: January 6, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Gullian Barre Syndrome
Drug: Eculizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study

Resource links provided by NLM:


Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:
  • Determine the incidence of AE/SAEs after treatment with eculizumab and IVIg compared to placebo controls [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Primary safety endpoint

  • Improvement of one or more grade in functional outcome (on the 6 point GBS disability scale) at 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Primary efficacy endpoint


Secondary Outcome Measures:
  • Ability to walk unaided (GBS disability score 2) at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Time taken to improve by at least one grade (on the GBS disability scale) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Time taken to walk independently [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Difference in GBS disability score at maximum disability completed with 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Percentage of patients with a clinically relevant improvement in R-ODS score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    An increase from Baseline in R-ODS score by at least 6 points on the centile metric score at 4 weeks and 6 months

  • Percentage of patients with a clinically relevant improvement in ONLS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Defined as an increase from baseline in ONLS score by at least 1 point at 4 weeks and 6 months

  • Requirement for ventilatory support (GBS disability score 5) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Duration of ventilatory support [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Occurrence of relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Dearth within the first 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab
Eculizumab, 900 mg intravenously once a week
Drug: Eculizumab
Placebo Comparator: Placebo
Matched placebo, intravenously once a week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT02029378

Contacts
Contact: Govindsinh Chavada govindsinh.chavada@glasgow.ac.uk
Contact: Ian Anderson 0141 201 2457 ian.anderson2@ggc.scot.nhs.uk

Locations
United Kingdom
Southern General Hospital Not yet recruiting
Glasgow, United Kingdom, G51 4TF
Contact: Govindsinh Chavada       govindsinh.chavada@glasgow.ac.uk   
Contact: Amy Davidson, MBChB, BSc, MRCP       amy.davidson2@nhs.net   
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
  More Information

No publications provided

Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT02029378     History of Changes
Other Study ID Numbers: GN12NE462
Study First Received: January 6, 2014
Last Updated: January 6, 2014
Health Authority: United Kingdom: National Health Service

Additional relevant MeSH terms:
Syndrome
Guillain-Barre Syndrome
Disease
Pathologic Processes
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Polyneuropathies
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014