An Open-Label Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of a Single Dose of ANX005 in Participants With Guillain-Barré Syndrome

The primary objective is to characterize the pharmacokinetic profile of a single dose of ANX005 30 mg/kg in participants recently diagnosed with Guillain-Barré syndrome from North America and Europe. This evaluation is clinically relevant to establish the drug disposition and exposure characteristics in the acute phase of this immune-mediated polyneuropathy, informing appropriate dosing strategies for this patient population.

The secondary objectives include:

• To characterize the pharmacodynamic profile of a single dose of ANX005 30 mg/kg in participants recently diagnosed with Guillain-Barré syndrome from North America and Europe

• To compare the efficacy of a single dose of ANX005 30 mg/kg on muscle strength in participants recently diagnosed with Guillain-Barré syndrome from North America and Europe relative to an external IGOS established benchmark

This clinical trial enrolled a total of **20 participants** recently diagnosed with **Guillain-Barré Syndrome** (GBS). The study population included both **male and female** participants aged **12 through 85 years** at the time of enrollment, encompassing adolescents, adults, and elderly individuals. Participants were selected based on a confirmed diagnosis of GBS according to the National Institute of Neurological Disorders and Stroke (NINDS) Diagnostic Criteria, with onset of GBS-related weakness occurring within 10 days or less before the first infusion. Eligible participants were required to have a GBS Disability Scale (GBS-DS) score of 3, 4, or 5 at screening and prior to treatment initiation, indicating moderate to severe functional impairment. Female participants of childbearing potential were required to use acceptable contraceptive methods during the study and for at least 30 days following study drug administration. All participants were expected to abstain from drugs of abuse during the study period and to undergo drug testing if substance use was suspected. The trial required participants to be capable of complying with all study requirements, completing protocol-related procedures and evaluations both during hospitalization and at outpatient follow-up visits, and providing written informed consent or assent.

This is an open-label, single-arm clinical trial designed to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and safety of a single dose of **ANX005** (tanruprubart), a **humanised IgG4 monoclonal antibody against C1q**, in participants with **Guillain-Barré syndrome**. The study is classified as a **Phase III** trial. The investigational medicinal product will be administered as a single **intravenous infusion** at a dose of **30 mg/kg**. The trial does not employ randomization or blinding procedures, as all participants will receive the active treatment in an open-label fashion.

The primary objective is to characterize the **pharmacokinetic profile** of ANX005 following a single dose administration in participants recently diagnosed with Guillain-Barré syndrome from North America and Europe. Secondary objectives include assessment of pharmacodynamic effects, specifically changes in **free C1q protein concentration** and **complement pathway activity** in serum, as well as evaluation of efficacy through the **Medical Research Council sumscore** change from baseline. The primary endpoints focus on **noncompartmental pharmacokinetic parameters** measured in serum through Week 2, while secondary endpoints assess pharmacodynamic markers through Week 2 and clinical efficacy at Week 1.

Eligible participants include male or female individuals aged 12 through 85 years who meet the **National Institute of Neurological Disorders and Stroke diagnostic criteria** for Guillain-Barré syndrome. Key inclusion criteria require onset of GBS-related weakness within 10 days or less before the planned infusion on Day 1, and a **GBS Disability Score** of 3, 4, or 5 at screening and before infusion. Participants must be able to comply with all study requirements, including completion of protocol-related procedures and evaluations during hospitalization and at outpatient follow-up visits. Female participants of childbearing potential must use acceptable contraception methods during the study and for at least 30 days following study drug infusion.

The trial is scheduled to commence recruitment in January 2026, with an estimated completion date in August 2026. Participants will undergo a screening visit to confirm eligibility and establish baseline measurements. Following enrollment, the investigational product will be administered on Day 1 during the initial hospitalization period. Subsequent follow-up visits will occur through Week 2 for intensive pharmacokinetic and pharmacodynamic assessments, with additional evaluations extending beyond this period to monitor clinical outcomes and safety parameters. The end-of-study visit will mark the completion of all protocol-specified assessments and the conclusion of participant involvement in the trial. Conditions that may lead to early termination from the study include withdrawal of consent, development of safety concerns requiring discontinuation, inability to comply with study procedures, or at the discretion of the investigator if continued participation is not in the best interest of the participant.

The experimental medicinal product in this clinical trial is **ANX005**, a **humanised IgG4 monoclonal antibody against C1q**. The active substance is classified as a protein of other origin. ANX005 is manufactured by Annexon, Inc. and has been designated as an **orphan drug** under the designation number EMA/OD/0000139967. The pharmaceutical form is an **intravenous infusion** solution.

ANX005 is administered as a **single dose** via **intravenous infusion**. The dosage is **30 mg/kg** based on body weight. The maximum daily dose is 30 mg/kg, which also represents the maximum total dose for the treatment period. The treatment period is limited to 1 day, reflecting the single-dose administration schedule.

The study is designed as an **open-label** trial to evaluate the **pharmacokinetics**, **pharmacodynamics**, **efficacy**, and **safety** of ANX005 in participants recently diagnosed with **Guillain-Barré syndrome**. The primary objective focuses on characterizing the pharmacokinetic profile of the single dose of ANX005 at 30 mg/kg in participants from North America and Europe. The role of ANX005 in this trial is classified as a test product, indicating its investigational nature in this therapeutic context.

Efficacy will be assessed through a combination of pharmacodynamic, clinical, and functional parameters. The primary endpoints include noncompartmental pharmacokinetic parameters of ANX005 in serum through Week 2. Secondary efficacy endpoints comprise change from baseline in free C1q protein concentration in serum through Week 2, change from baseline in percent complement pathway activity in serum through Week 2, and Medical Research Council sumscore change from baseline at Week 1. These measurements will evaluate both the pharmacodynamic effects of the investigational medicinal product on complement pathway components and the clinical improvement in muscle strength in participants with Guillain-Barré syndrome. The assessments will be conducted at specified timepoints including Week 1 and Week 2, with baseline measurements serving as the reference point for evaluating changes in the measured parameters.