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

NCT ID: NCT02029378

Last Updated: 2014-09-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2016-03-31

Brief Summary

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.

Conditions

Gullian Barre Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Eculizumab

Eculizumab, 900 mg intravenously once a week

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

Placebo

Matched placebo, intravenously once a week

Group Type: PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

Eculizumab

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Southern General Hospital

Glasgow, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Govindsinh Chavada

Role: CONTACT

govindsinh.chavada@glasgow.ac.uk

Ian Anderson

Role: CONTACT

ian.anderson2@ggc.scot.nhs.uk

0141 201 2457

Facility Contacts

Govindsinh Chavada

Role: primary

govindsinh.chavada@glasgow.ac.uk

Amy Davidson, MBChB, BSc, MRCP

Role: backup

amy.davidson2@nhs.net

References

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.

Reference Type: DERIVED

PMID: 27801990 (View on PubMed)

Other Identifiers

GN12NE462

Identifier Type: -

Identifier Source: org_study_id