A Phase III Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Patients With Guillain-Barré Syndrome
Overview
- Phase
- Phase 3
- Intervention
- Crovalimab
- Conditions
- Guillain-Barré Syndrome
- Sponsor
- Hoffmann-La Roche
- Primary Endpoint
- Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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)
Arms & Interventions
Crovalimab
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.
Intervention: Crovalimab
Crovalimab
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.
Intervention: Intravenous immunoglobulin therapy
Placebo
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.
Intervention: Placebo
Placebo
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.
Intervention: Intravenous immunoglobulin therapy
Outcomes
Primary Outcomes
Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24
Time Frame: 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).
Secondary Outcomes
- Percentage of Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Responders at Week 24(Week 24)
- Time to Recover Independent Walking Assessed Using the 10-Meter Walk Test (10-MW)(Up to approximately 52 weeks)
- Percentage of Participants with Treatment Emergent Adverse Events(Up to approximately 52 weeks)
- Functional Outcome on GBS-DS at Week 8(Week 8)
- Duration of Ventilator Support(Randomization to Week 24)
- Percentage of Participants with Anti-Drug Antibodies to Crovalimab(Up to approximately 52 weeks)
- Mean Post-Recovery Time(Randomization to Week 24)
- Percentage of Participants with Treatment Emergent Adverse Events Leading to Study Drug Discontinuation(Up to approximately 52 weeks)
- Serum Concentrations of Crovalimab(From Day 1 up to Week 52)