A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)

NCT05494619 | Withdrawn Phase 3 FDA Drug

• 2 other identifiers: BN431182021-002968-49
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab compared with placebo as an add-on therapy to intravenous immunoglobulin (IVIg) in participants with severe GBS.

Conditions

Guillain-Barré Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24

  The Guillain-Barré Syndrome disability score (GBS DS) is used to assess the degree of functional disability of study participants. The scale consists of seven grades of functional disability ranging from 0 (healthy with no symptoms attributable to GBS) to 6 (death).

  Week 24

Secondary Outcomes (9)

• Time to Recover Independent Walking Assessed Using the 10-Meter Walk Test (10-MW)

  Up to approximately 52 weeks

• Functional Outcome on GBS-DS at Week 8

  Week 8

• Percentage of Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Responders at Week 24

  Week 24

• Mean Post-Recovery Time

  Randomization to Week 24

• Duration of Ventilator Support

  Randomization to Week 24

Study Arms (2)

Crovalimab

EXPERIMENTAL

Participants will receive a single intravenous (IV) infusion of crovalimab on Day 1 based on body weight, followed by crovalimab subcutaneous (SC) injection on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, intravenous immunoglobulin (IVIg) background therapy will be administered once a day (QD) for 5 days.

Drug: Crovalimab; Drug: Intravenous immunoglobulin therapy

Placebo

PLACEBO COMPARATOR

Participants will receive a single IV infusion of placebo on Day 1 based on body weight, followed by placebo SC injections on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, IVIg background therapy will be administered QD for 5 days.

Drug: Placebo; Drug: Intravenous immunoglobulin therapy

Interventions

Crovalimab DRUG

Crovalimab will be administered at a dose of 1000 milligrams (mg) IV (for participants with body weight ≥ 40 kilograms (kg) and \<100 kg) or 1500 mg IV (for participants with body weight ≥ 100 kg) on Day 1, followed by crovalimab 340 mg SC injections on Days 2, 8, 15 and 22 in all participants.

Crovalimab

Placebo DRUG

Placebo will be administered IV on Day 1 at a dose of 1000 mg for participants with body weight ≥ 40 kg to \< 100 kg, or 1500 mg for participants with body weight ≥ 100 kg. It will be administered SC on Days 2, 8, 15, and 22 at a dose 340 mg in all participants.

Placebo

Intravenous immunoglobulin therapy DRUG

All participants will receive background therapy of IVIg at a dose of 400 milligrams/kilograms (mg/kg) QD for 5 days.

Crovalimab; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body weight \>= 40 kg at screening
• Confirmed diagnosis of GBS according to National Institute of Neurological Disorders and Stroke (NINDS) classification system
• Onset of weakness due to GBS within 2 weeks before randomization
• Able to start the first dose of blinded study drug within 2 weeks of onset of weakness
• Able to climb a flight of stairs prior to GBS
• Unable to walk independently for \>=10 meters (FG \>=3) with deteriorating weakness as per investigator judgment, or FG 4 or FG 5 on the GBS-DS. These criteria must be satisfied during screening.
• Undergoing or starting IVIg treatment (400 mg/kg QD for 5 days) prior to first blinded study drug administration. Participants must be able to receive the first dose of blinded study drug before the final dose of IVIg during the 5-day period of IVIg treatment.
• A record of vaccination (\<=3 years) against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumonia prior to initiation of blinded study drug, in accordance with most current local guidelines as applicable for patients with complement deficiency.
• Adequate hepatic and renal function
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for up to 11 months after the final dose of study treatment.

You may not qualify if:

• Clear clinical and historical evidence of significant or disabling acute or chronic peripheral neuropathy of alternative etiology, chronic inflammatory demyelinating polyneuropathy, severe vitamin deficiency, porphyria, or diagnosis of Charcot Marie Tooth disease or other genetic neuropathy
• History of requiring a permanent aid to walk prior to GBS
• Treatment with plasmapheresis or PLEX after GBS diagnosis, or a plan to receive this treatment
• Receipt of systemic immunosuppressive treatment within 4 weeks prior to randomization
• Known or suspected hereditary complement deficiency
• Known or suspected immune deficiency
• Recent use (up to five half-lives) of treatment with complement inhibitors (e.g., 10 weeks for eculizumab, 41 weeks for ravulizumab)
• History of Neisseria meningitidis infection within 12 months prior to screening and up to first blinded study drug administration (Day 1)
• Contraindication that would prevent use of any class of antibiotics as Neisseria meningitides prophylaxis
• Immunization with a live attenuated vaccine within 1 month before first blinded study drug administration (Day 1)
• Participants who have been partially or fully vaccinated against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation.
• Recent SARS-CoV-2 infection (defined by a positive PCR test within the 2-week period prior to screening), or ongoing symptoms of active COVID-19
• Any systemic bacterial, viral, or fungal infection ongoing at screening and up to the first blinded study drug administration (Day 1) which, in the investigators' judgment, is active and could potentially be worsened by immunosuppression
• Current hepatitis B, hepatitis C, or HIV infection
• History of malignancy within 5 years prior to screening and up to the first blinded study drug administration (Day 1)

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical Co., Ltd. (Sponsor in Taiwan and Japan): collaborator

MeSH Terms

Conditions

Guillain-Barre Syndrome

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 10, 2022
• Study Start: November 30, 2022
• Primary Completion: March 19, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: December 15, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share