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

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ClinicalTrials.gov Identifier: NCT02029378
Recruitment Status : Unknown
Verified September 2014 by NHS Greater Glasgow and Clyde.
Recruitment status was:  Recruiting
First Posted : January 7, 2014
Last Update Posted : September 23, 2014
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Tracking Information
First Submitted Date  ICMJE January 6, 2014
First Posted Date  ICMJE January 7, 2014
Last Update Posted Date September 23, 2014
Study Start Date  ICMJE September 2014
Estimated Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2014)
  • Determine the incidence of AE/SAEs after treatment with eculizumab and IVIg compared to placebo controls [ Time Frame: 6 months ]
    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 ]
    Primary efficacy endpoint
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2014)
  • Ability to walk unaided (GBS disability score 2) at 8 weeks [ Time Frame: 8 weeks ]
  • Time taken to improve by at least one grade (on the GBS disability scale) [ Time Frame: 8 weeks ]
  • Time taken to walk independently [ Time Frame: 1 year ]
  • Difference in GBS disability score at maximum disability completed with 6 months [ Time Frame: 6 months ]
  • Percentage of patients with a clinically relevant improvement in R-ODS score [ Time Frame: 6 months ]
    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 ]
    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 ]
  • Duration of ventilatory support [ Time Frame: 8 weeks ]
  • Occurrence of relapse [ Time Frame: 2 years ]
  • Dearth within the first 6 months [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study
Official Title  ICMJE Inhibition of Complement Activation (Eculizumab) in Guillain-Barre Syndrome Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Gullian Barre Syndrome
Intervention  ICMJE Drug: Eculizumab
Study Arms  ICMJE
  • Experimental: Eculizumab
    Eculizumab, 900 mg intravenously once a week
    Intervention: Drug: Eculizumab
  • Placebo Comparator: Placebo
    Matched placebo, intravenously once a week
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-Barré syndrome: the ICA-GBS study. J Peripher Nerv Syst. 2017 Mar;22(1):4-12. doi: 10.1111/jns.12194.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 6, 2014)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2016
Estimated Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02029378
Other Study ID Numbers  ICMJE GN12NE462
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NHS Greater Glasgow and Clyde
Study Sponsor  ICMJE NHS Greater Glasgow and Clyde
Collaborators  ICMJE University of Glasgow
Investigators  ICMJE Not Provided
PRS Account NHS Greater Glasgow and Clyde
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP