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

A Phase 3, Prospective, Multicenter, Double Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Eculizumab in Patients With Guillain-Barré Syndrome (GBS)

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.

Study Overview

• Status: Completed
• Conditions: Guillain-Barre Syndrome
• Intervention / Treatment: Biological: Eculizumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyo-ku, Japan, 113-8519
    • Clinical Trial Site
  • Chiba, Japan, 260-8677
    • Clinical Trial Site
  • Fuchu, Japan, 183-0042
    • Clinical Trial Site
  • Fukuoka, Japan, 814-0180
    • Clinical Trial Site
  • Gifu, Japan, 501-1194
    • Clinical Trial Site
  • Hiroshima, Japan, 730-8518
    • Clinical Trial Site
  • Kagoshima, Japan, 890-8520
    • Clinical Trial Site
  • Kawagoe, Japan, 350-8550
    • Clinical Trial Site
  • Kawasaki, Japan, 216-8511
    • Clinical Trial Site
  • Kitakyushu, Japan, 807-8556
    • Clinical Trial Site
  • Kobe, Japan, 650-0047
    • Clinical Trial Site
  • Kumamoto, Japan, 860-8556
    • Clinical Trial Site
  • Kurashiki, Japan, 710-8602
    • Clinical Trial Site
  • Kyoto, Japan, 602-8566
    • Clinical Trial Site
  • Matsumoto, Japan, 390-8621
    • Clinical Trial Site
  • Mibu, Japan, 321-0293
    • Clinical Trial Site
  • Mitaka, Japan, 181-8611
    • Clinical Trial Site
  • Nagoya, Japan, 466-8560
    • Clinical Trial Site
  • Niigata, Japan, 951-8520
    • Clinical Trial Site
  • Nishinomiya, Japan, 663-8501
    • Clinical Trial Site
  • Osakasayama, Japan, 589-8511
    • Clinical Trial Site
  • Sagamihara, Japan, 252-0375
    • Clinical Trial Site
  • Sapporo, Japan, 060-8648
    • Clinical Trial Site
  • Sendai, Japan, 983-8520
    • Clinical Trial Site
  • Ube, Japan, 755-8505
    • Clinical Trial Site
  • Yokohama, Japan, 236-0004
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo.	Drug: Placebo; Placebo will be administered via IV infusion once a week for 4 weeks.
Experimental: Eculizumab; Participants will receive eculizumab.	Biological: Eculizumab; Eculizumab will be administered via IV infusion once a week for 4 weeks.; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Reaching a Hughes Functional Grade (FG) Score <=1	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.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With A Hughes Functional Grade (FG) Score <=1	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.	Week 8, Week 24
Number of Participants With A Hughes Functional Grade Score Improvement of >=3	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.	Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	Day 1 up to Week 24
Free Complement Component 5 in Serum		Week 24
Hemolytic Complement Activity in Serum		Week 24
Length of Stay in the Hospital	For participants with multiple hospitalizations, the total duration of all hospitalizations was summarized.	Up to Week 24
Number of Participants Who Required Mechanical Ventilator Support	For participants with more than 1 episode of the same support, the total duration across all episodes was summarized.	Up to Week 24
Concentration of Eculizumab in Serum		Up to Week 24
Number of Participants With Positive Antidrug Antibodies		Up to Week 12

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Actual): August 3, 2022
• Study Completion (Actual): August 3, 2022

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Eculizumab; Soliris; Alexion; C5 Inhibition Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Polyneuropathies; Chronic Disease; Post-Infectious Disorders; Syndrome; Guillain-Barre Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: ECU-GBS-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No