A Study to Evaluate the Efficacy and Safety of Eculizumab in Guillain-Barré Syndrome

Phase 3

Completed

Conditions: Guillain-Barre Syndrome

Interventions: Biological: Eculizumab
Drug: Placebo

Registration Number: NCT04752566

Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary: This is a Phase 3, prospective, multicenter, placebo controlled, double blind, randomized study to investigate the efficacy and safety of eculizumab in participants with severe GBS, defined using the Hughes Functional Grade (FG) scale as progressively deteriorating FG3 or FG4/FG5 within 2 weeks from onset of weakness due to GBS.

This study will be conducted only at sites in Japan.

Detailed Description: Eligible participants will be randomized to receive intravenous (IV) infusion of eculizumab or placebo at a 2:1 ratio. All participants will be on concomitant IV immunoglobulin G (Ig) therapy as per standard of care.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

Inclusion Criteria

Participants who meet the GBS criteria.
Participants who were able to run prior to onset of GBS symptoms.
Participants with onset of weakness due to GBS < 2 weeks before screening.
Participants unable to walk unaided for ≥ 5 meters (progressively deteriorating FG3 or FG4 to FG5).
Participants who are already on IVIg or deemed eligible for and who will start IVIg.
Participants who can start their first dose of study drug before the end of the IVIg treatment period.

Exclusion Criteria

Participants who have previously received or are currently receiving treatment with complement modulators.
Participants who have been administered another investigational product within 30 days or 5 half-lives (whichever is longer) prior to providing consent or are currently participating in another interventional study.
Participants who have received rituximab within 12 weeks prior to screening.
Participants who are being considered for or are already on plasmapheresis.
Participants who have received immunosuppressive treatment during the 4 weeks prior to providing consent.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eculizumab	Eculizumab	Participants will receive eculizumab.
Placebo	Placebo	Participants will receive placebo.

Primary Outcome Measures

Name	Time	Method
Time to First Reaching a Hughes Functional Grade (FG) Score <=1	Up to Week 24	The mobility of the participants was evaluated on a 7 point disability functional grade scale and described as Hughes FG score of 0 (Healthy, no signs or symptoms of Guillain-Barré syndrome); 1 (Minor signs or symptoms and able to run); 2 (Able to walk 5 metre (m) across an open space without assistance); 3 (Able to walk 5 m across an open space with the help of one person and waist-level walking-frame, stick, or sticks); 4 (Chairbound/bedbound: unable to walk as in 3); 5 (Requiring assisted ventilation \[for at least part of day or night\]) and 6 (Dead), where higher numbers indicate more severe impairment. The Kaplan-Meier estimate of time to event of FG\<=1 is reported. Time (days) to first event=Date of first event-Date of first dose+1. Participants who discontinued early without achieving FG \<= 1 were censored at the date of discontinuation. Participants who completed the study without achieving FG\<=1 were censored at the date of study completion.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With A Hughes Functional Grade (FG) Score <=1	Week 8, Week 24	The mobility of the participants was evaluated on a 7 point disability FG scale and described as Hughes FG score of 0 (Healthy, no signs or symptoms of Guillain-Barré syndrome); 1 (Minor signs or symptoms and able to run); 2 (Able to walk 5 m across an open space without assistance); 3 (Able to walk 5 m across an open space with the help of one person and waist-level walking-frame, stick, or sticks); 4 (Chairbound/bedbound: unable to walk as in 3); 5 (Requiring assisted ventilation \[for at least part of day or night\]) and 6 (Dead), where higher numbers indicate more severe impairment. If a participant had an FG score \<= 1 prior to or at Week 8 and Week 24, respectively, then the participant is considered a responder. Otherwise, participants discontinued prior to Week 8 and Week 24 or with an FG score \> 1 at Week 8 and Week 24 are nonresponders, respectively.
Free Complement Component 5 in Serum	Week 24
Number of Participants Who Required Mechanical Ventilator Support	Up to Week 24	For participants with more than 1 episode of the same support, the total duration across all episodes was summarized.
Number of Participants With A Hughes Functional Grade Score Improvement of >=3	Week 24	The mobility of the participants was evaluated on a 7 point disability FG scale and described as Hughes FG score of 0 (Healthy, no signs or symptoms of Guillain-Barré syndrome); 1 (Minor signs or symptoms and able to run); 2 (Able to walk 5 m across an open space without assistance); 3 (Able to walk 5 m across an open space with the help of one person and waist-level walking-frame, stick, or sticks); 4 (Chairbound/bedbound: unable to walk as in 3); 5 (Requiring assisted ventilation \[for at least part of day or night\]) and 6 (Dead), where higher numbers indicate more severe impairment. Participants with a change from baseline in FG score (value at Week 24 - baseline value) \<= -3 were considered a responder. Participants with change from baseline \> -3 and participants who discontinued prior to Week 24 were considered non-responders.
Hemolytic Complement Activity in Serum	Week 24
Length of Stay in the Hospital	Up to Week 24	For participants with multiple hospitalizations, the total duration of all hospitalizations was summarized.
Concentration of Eculizumab in Serum	Up to Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Week 24	TEAEs were defined as an adverse event (AE) with onset on or after the first dose of the study drug. An AE is any untoward medical occurrence in a participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Number of Participants With Positive Antidrug Antibodies	Up to Week 12