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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Guillain-Barre Syndrome	Biological: Eculizumab; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: March 8, 2021
• Actual Primary Completion Date: August 3, 2022
• Actual Study Completion Date: August 3, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. Free Complement Component 5 in Serum [ Time Frame: Week 24 ]
5. Hemolytic Complement Activity in Serum [ Time Frame: Week 24 ]
6. 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.
7. 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.
8. Concentration of Eculizumab in Serum [ Time Frame: Up to Week 24 ]
9. Number of Participants With Positive Antidrug Antibodies [ Time Frame: Up to Week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Japan

Clinical Trial Site

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

Sponsors and Collaborators

Alexion Pharmaceuticals, Inc.

  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals, Inc.:

Study Protocol  [PDF] October 28, 2021

Statistical Analysis Plan  [PDF] June 30, 2022

More Information

• Responsible Party: Alexion Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04752566
• Other Study ID Numbers: ECU-GBS-301
• First Posted: February 12, 2021
• Results First Posted: February 9, 2024
• Last Update Posted: February 9, 2024
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Alexion Pharmaceuticals, Inc.:

Eculizumab; Soliris; Alexion; C5 Inhibition Therapy

Additional relevant MeSH terms:

Guillain-Barre Syndrome; Syndrome; Disease; Pathologic Processes; Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Eculizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs