Clinical Trial: JET-GBS - Japanese Eculizumab Trial for GBS

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A PROSPECTIVE, MULTI-CENTER, PHASE II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ECULIZUMAB IN SUBJECTS WITH GUILLAIN-BARRÉ SYNDROME

Brief Summary:

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that usually follows an antecedent infection and causes acute neuromuscular paralysis. GBS is currently classified into the two major subtypes: a classical demyelinating type and axonal variant type. Whereas in Europe and North America demyelinating GBS is the major subtype, in East Asia and Central and South America, axonal GBS is found in 30~65% of patients. Although the pathophysiology of GBS has not been fully understood, major advances have been made in understanding the pathophysiology particularly for the axonal form of GBS. It is now established that axonal GBS is caused by molecular mimicry of human gangliosides by the Campylobacter jejuni lipo-oligosaccharides. Autoantibodies bind to GM1 or GD1a at the nodes of Ranvier, activate complements, and disrupt sodium channel clusters and axo-glial junctions, resulting in the nerve conduction failure and muscle weakness. C. jejuni infection induces production of antibodies, which cross-react with gangliosides on the human nerve axolemma, and activate the complements, resulting in formation of membrane attack complex (MAC). The pathology leads to axonal degeneration.

The standard treatments for GBS are plasma exchange and intravenous immunoglobulin and the disease progression reaches its nadir within 4 weeks. However, during the acute phase, 18-28 % of the patients require artificial ventilation and 4.1-6.3 % of the patients die of complications. Recovery takes several months or years, and 16.7-19.7 % of the patients still require aid to walk one year after onset. Because of such serious disability of GBS patients, an alternative novel therapy that can prevent death during acute phase or severe sequelae is needed.

Eculizumab is a humanized monoclonal antibody of murine anti-human C5 antibody and speci

Detailed Summary:
Sponsor: Chiba University

Current Primary Outcome:

  • [Safety] Expressed frequency and severity of incidence of AE/SAEs after treatment with investigational product. [ Time Frame: 6 months ]
  • [Efficacy] Proportion of subjects who reach a score of FG2 or lower on the Hughes functional grading scale at week 4（Response Rate） [ Time Frame: 4 weeks ]


Original Primary Outcome:

  • The incidence of AE/SAEs after treatment with eculizumab and IVIg compared to placebo controls [ Time Frame: 6 months ]
  • Improvement of one or more grade in functional outcome (on the 6 point GBS disability scale) at 4 weeks [ Time Frame: 4 weeks ]


Current Secondary Outcome:

  • Proportion of subjects with improvement of one or more scores on the functional grading scale at each visit [ Time Frame: 6 months ]
  • Proportion of subjects who are able to walk unaided (FG2 or lower) at each visit [ Time Frame: 6 months ]
  • Duration required for improvement by at least one grade on the Hughes functional grading scale [ Time Frame: 6 months ]
  • 5. Change in the FG score between peak disability score and the scores at each visit [ Time Frame: 6 months ]
  • Proportion of subjects with a clinically relevant improvement in the R-ODS score. An increase in the R-ODS score (0-48) converted to the centile metric score (0-100) by at least six points at each visit [ Time Frame: 6 months ]
  • Proportion of subjects with a clinically relevant improvement in ONLS. (a decrease in the ONLS score from baseline by at least 1 point) at each visit [ Time Frame: 6months ]
  • Proportion and frequency of subjects who require ventilatory support (F 5) [ Time Frame: 4 weeks ]
  • Duration of ventilatory support [ Time Frame: 8 weeks ]
  • Occurrence of relapse from the start of the IP(Investigational Product) administration period until the end of the post IP period [ Time Frame: 2 years ]
  • Overall survival from the start of the IP administration period until the end of the post IP period (OS) [ Time Frame: 6 months ]
  • Change in grip strength at each visit from baseline [ Time Frame: 6 months ]
  • Change in results of the manual muscle test (MMT score) at each visit from baseline [ Time Frame: 6 months ]
  • Change in the rate and results of below measures on the nerve conduction test parameter from baseline:Median and ulnar nerve 's CMAP amplitude, distal latency, F wave latency , SNAP amplitude, motor sensory nerve conduction velocity [ Time Frame: 6 months ]
  • Change in vital capacity and % vital capacity at each visit from baseline [ Time Frame: 6 months ]
  • Proportion of patients who undergo re-administration of IVIg [ Time Frame: 6 months ]


Original Secondary Outcome:

  • 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: up to 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: 6months ]
    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 ]


Information By: Chiba University

Dates:
Date Received: July 7, 2015
Date Started: July 2015
Date Completion: October 2016
Last Updated: April 23, 2016
Last Verified: April 2016