Randomized, Quadruple-Blind, Placebo-Controlled Phase 2b Study of Batoclimab in Adults with Active Chronic Inflammatory Demyelinating Polyneuropathy

The primary objective of this study is to evaluate the **efficacy** of batoclimab compared to placebo in maintaining clinical response in participants with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). This is assessed using the adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score in participants receiving immune globulin (IVIg or SCIg) or plasma exchange (PLEX) treatment at the time of screening. The clinical relevance of this objective lies in its potential to provide a new therapeutic option for maintaining clinical response in CIDP, a chronic neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms.

Secondary objectives include:

• Evaluating the efficacy of batoclimab compared to placebo in maintaining clinical response in participants receiving any CIDP treatment at the time of screening, across Cohorts A and B combined.
• Assessing the efficacy of batoclimab compared to placebo in maintaining clinical response regardless of CIDP treatment history, across Cohorts A, B, and C combined.

The clinical trial involves a total of **99 participants** diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The study population includes both male and female subjects, aged 18 years and older, who are currently receiving immune globulin or plasma exchange treatment for CIDP. Participants were selected based on their clinical diagnostic criteria for typical CIDP or its variants, such as multifocal, focal, or motor CIDP, in accordance with the EAN/PNS Guideline on the Diagnosis and Treatment of CIDP. The trial includes individuals with electrodiagnostic test results supporting the diagnosis of CIDP. The study population is characterized by a diverse age range and includes a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria require participants to have met specific clinical and electrodiagnostic criteria for CIDP, ensuring a well-defined study cohort.

The clinical trial is a **Phase 2b**, multi-center, randomized, quadruple-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Batoclimab** in adult participants with active **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The trial involves a comparison between Batoclimab and a placebo, which is identical to the investigational medicinal product (IMP) but contains no active substance. The study is structured to maintain clinical response as assessed by the adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score in participants receiving immune globulin or plasma exchange treatment for CIDP at the time of screening.

The trial is expected to run from November 2022 to January 2027, with an estimated participant involvement duration of up to 88 weeks. Participants will be randomly assigned to receive either Batoclimab or placebo via subcutaneous injection. The study includes several key visits: an initial screening visit to confirm eligibility based on specific inclusion criteria, including age and diagnostic criteria for CIDP, followed by regular follow-up visits to monitor the participants' health and response to treatment. The primary endpoint is the proportion of participants who remain relapse-free at Week 36, with secondary endpoints including time to first relapse and changes in various disability and strength scores.

Participants will be required to attend scheduled visits throughout the study period, including an end-of-study visit to assess the final outcomes. Conditions that may lead to early termination from the study include significant adverse events or failure to adhere to the study protocol. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants. The study's design and methodology are aligned with the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines for the diagnosis and treatment of CIDP, ensuring a robust and scientifically sound approach to evaluating the investigational treatment's efficacy and safety.

The clinical trial involves the administration of **Batoclimab**, a solution for injection, as the experimental medication. Batoclimab is a human monoclonal antibody targeting the human FcRn receptor, with the active substance name **BATOCLIMAB**. It is also known by synonyms such as HL161BKN, HBM-9161, and RVT-1401. The pharmaceutical form of Batoclimab is a solution for injection, and it is administered via subcutaneous injection. The maximum daily dose is 680 mg, with a total maximum dose of 35,360 mg over a treatment period of 88 days. The administration schedule and participant compliance are monitored throughout the trial to ensure adherence to the dosing regimen.

The study also includes a **placebo** group, where participants receive a placebo that is identical in appearance to the investigational medicinal product (IMP) but contains no active substance. The placebo is used to maintain the quadruple-blind design of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same pharmaceutical form and route as Batoclimab, ensuring consistency in the administration process across all study groups.

Participants in the trial may also be receiving standard-of-care therapies such as immune globulin (IVIg or SCIg) or plasma exchange (PLEX) for the treatment of **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)** at the time of screening. These treatments are not part of the experimental protocol but are considered in the evaluation of Batoclimab's efficacy in maintaining clinical response as assessed by the adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score.

The efficacy of Batoclimab in the treatment of **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)** will be assessed through a series of primary and secondary endpoints. The primary endpoint for Period 2, Cohort A, is the proportion of participants who remain relapse-free at Week 36. Relapse is defined as a worsening of ≥ 1 point on the adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score at any time point during Period 2 relative to the baseline, sustained at a follow-up visit one week later.

Secondary endpoints include the time to first relapse relative to the Period 2 baseline and changes from the Period 2 baseline to Week 36 in several measures: Adj INCAT score, Inflammatory Rasch-built Overall Disability Scale (I-RODS), Mean Grip Strength, Medical Research Council (MRC) Sum Score, and Overall Neuropathy Limitations Scale (ONLS). These secondary endpoints will be evaluated for Period 2, Cohort A, and for combined Cohorts A and B. Additionally, the proportion of participants who remain relapse-free at Week 36 will be assessed for combined Cohorts A, B, and C.