Objective:

Characterize the pharmacokinetics, pharmacodynamics, efficacy, and safety of tanruprubart 30 mg/kg in participants with Guillain-Barré syndrome (GBS) from North America and Europe.

Background:

GBS is a neuromuscular emergency driven by classical complement activation that, despite current treatments, leads to significant morbidity and mortality in previously healthy individuals. Tanruprubart, a monoclonal antibody targeting C1q, the initiating molecule of classical complement, has been studied in a Phase 3, randomized, double-blind, placebo-controlled study in patients with GBS in southeast Asia. Tanruprubart 30 mg/kg was well tolerated and participants were 2.4 times more likely to be in a better state of health (GBS-DS; p=0.0058) versus placebo at Week 8 with rapid improvement in muscle strength (MRCss) from Week 1.

Design/Methods:

GBS-FORWARD is a multicenter, open-label, single-arm study of single intravenous administration tanruprubart 30 mg/kg in US and European participants recently diagnosed with GBS. Participants must be 12–85 years old, have a GBS diagnosis per NINDS criteria, with onset of GBS-related weakness ≤10 days before infusion on Day 1. Participants will remain hospitalized from screening until assessment completion on Day 8 or until medically cleared for release, whichever occurs later. Participants will have follow-up visits through Week 26 and receive best supportive care, omitting intravenous immunoglobulin or plasma exchange unless as a rescue treatment.

Results:

Approximately 30 participants are planned for enrollment. The primary objective is to characterize the pharmacokinetics of a single tanruprubart dose, which will enable comparison with pharmacokinetic data obtained from previous studies in participants from Southeast Asia. The study is powered to compare MRC sumscore at Week 1 with an IVIg-treated, external control group from the International GBS Outcome Study database.

Conclusions:

This study will add to the extensive body of evidence showing the benefit of tanruprubart in patients with GBS and confirm previous study findings in a population from North America and Europe.