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

• ClinicalTrials.gov Identifier: NCT04752566
• Recruitment Status: Completed
• First Posted: February 12, 2021
• Results First Posted: February 9, 2024
• Last Update Posted: February 9, 2024
• Sponsor: Alexion Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Alexion Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: February 9, 2021
• First Posted Date: February 12, 2021
• Results First Submitted Date: June 6, 2023
• Results First Posted Date: February 9, 2024
• Last Update Posted Date: February 9, 2024
• Actual Study Start Date: March 8, 2021
• Actual Primary Completion Date: August 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 6, 2023)

Time to First Reaching a Hughes Functional Grade (FG) Score <=1 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: February 9, 2021): Time To First Reaching A Hughes FG Score ≤ 1 [ Time Frame: Up to Week 24 ]

Current Secondary Outcome Measures (submitted: June 6, 2023)

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

Original Secondary Outcome Measures (submitted: February 9, 2021)

• Proportion Of Participants With A Hughes FG Score ≤ 1 [ Time Frame: Week 24 ]
• Proportion Of Participants With A Hughes FG Score Improvement Of ≥ 3 [ Time Frame: Week 24 ]
• Proportion Of Participants With A Hughes FG Score ≤ 1 [ Time Frame: Week 8 ]
• Incidence Of Treatment-emergent Adverse Events [ Time Frame: Up to Week 24 ]
• Free Complement Component 5 In Serum [ Time Frame: Week 24 ]
• Hemolytic Complement Activity In Serum [ Time Frame: Week 24 ]
• Length Of Stay In The Hospital [ Time Frame: Up to Week 24 ]
• Duration Of Ventilator Support [ Time Frame: Up to Week 24 ]
• Concentration Of Eculizumab In Serum [ Time Frame: Up to Week 24 ]
• Incidence Of Antidrug Antibodies [ Time Frame: Up to Week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Eculizumab in Guillain-Barré Syndrome
• Official Title: 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)

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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Guillain-Barre Syndrome

Intervention

• Biological: Eculizumab
  Eculizumab will be administered via IV infusion once a week for 4 weeks.
  Other Name: Soliris
• Drug: Placebo
  Placebo will be administered via IV infusion once a week for 4 weeks.

Study Arms

• Experimental: Eculizumab
  Participants will receive eculizumab.
  Intervention: Biological: Eculizumab
• Placebo Comparator: Placebo
  Participants will receive placebo.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 9, 2021): 57
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 3, 2022
• Actual Primary Completion Date: August 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04752566
• Other Study ID Numbers: ECU-GBS-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Alexion Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alexion Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alexion Pharmaceuticals, Inc.
• Verification Date: May 2023