Efficacy and Safety of Nipocalimab in Adults with Chronic Inflammatory Demyelinating Polyneuropathy: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of nipocalimab compared to placebo in delaying relapse in participants with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)** who initially respond to nipocalimab in Stage A. This is clinically relevant as it aims to determine the potential of nipocalimab to maintain disease stability and prevent relapse, which is crucial for improving patient outcomes in CIDP.

Secondary objectives include:

• Stage A - To assess improvement of symptoms on nipocalimab.
• Stage A - To assess improvement in disease severity and progression on nipocalimab.
• Stage B - To evaluate the efficacy of nipocalimab compared to placebo on time to CIDP disease progression from Stage B baseline.
• Stage B - To evaluate the efficacy of nipocalimab compared to placebo on improved functional level compared to Stage B baseline.
• Other secondary - To assess the safety and tolerability of nipocalimab compared to placebo.
• Other secondary - To assess the pharmacokinetics (PK) and immunogenicity of nipocalimab.
• Other secondary - To evaluate the pharmacodynamics (PD) of nipocalimab.

The clinical trial involves a total of **152 participants** diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The study population includes both male and female adults aged 18 years and older, who meet the legal age of consent in their respective jurisdictions. Participants were selected based on a diagnosis of CIDP according to the EAN/PNS 2021 criteria, specifically those with progressing or relapsing forms of the condition. An independent committee adjudicated the diagnosis during the screening period. The trial includes individuals with an adjusted INCAT disability score between 2 and 9, with a score of 2 being exclusively from leg disability. The study population is diverse, encompassing a range of ages and both genders, and includes vulnerable populations. Lifestyle considerations such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **Phase 2/3**, multistage, multicenter, randomized, double-blind, placebo-controlled parallel group withdrawal study designed to evaluate the efficacy and safety of **nipocalimab** in adults with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The primary objective is to assess the efficacy of nipocalimab compared to placebo in delaying relapse in participants who initially respond to nipocalimab in Stage A. The trial is expected to conclude by July 31, 2030, with recruitment having commenced on January 2, 2023.

Participants will be randomly assigned to receive either nipocalimab or a placebo. The study involves multiple stages, with the initial stage focusing on the response to nipocalimab. The trial will include a screening visit to confirm eligibility based on criteria such as age, diagnosis of CIDP according to EAN/PNS 2021 criteria, and an adjusted INCAT disability score between 2 and 9. Following the screening, participants will undergo regular follow-up visits to monitor their response to the treatment and any adverse events. The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment.

The expected duration of participant involvement varies, with the maximum treatment period for nipocalimab being 66 weeks. Participants may be withdrawn from the study early if they experience a relapse, defined by a deterioration in the adjusted INCAT disability score or a switch to intravenous immunoglobulin (IVIg) or other standard of care due to lack of efficacy. Secondary endpoints include changes in muscle strength, grip strength, and other clinical measures over time, as well as the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Throughout the trial, participants will receive either a **solution for injection** or a **solution for infusion** of nipocalimab, with the route of administration being **intravenous use**. The study will also monitor serum nipocalimab concentrations and the presence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) to nipocalimab. The trial is not classified as a low-intervention study and is conducted under the sponsorship of Janssen-Cilag International N.V.

The clinical trial involves the administration of **nipocalimab**, an experimental medication, under the product name JNJ-80202135. Nipocalimab is provided in two pharmaceutical forms: a **solution for injection** and a **solution for infusion**. The solution for injection is administered intravenously, with a maximum treatment period of 29 days. The solution for infusion is also administered intravenously, with a maximum treatment period of 66 days. Both forms are developed by Janssen-Cilag International N.V. and contain the active substance nipocalimab, a protein-based monoclonal antibody targeting the neonatal Fc receptor. The dosing schedule and frequency of administration are determined by the study protocol, and participant compliance is monitored throughout the trial.

In addition to the experimental treatment, the study includes the use of **Privigen**, a 100 mg/ml solution for infusion containing **human normal immunoglobulin**. This comparator treatment is administered intravenously and is produced by CSL Behring GmbH. The maximum treatment period for Privigen is 3 days. The role of Privigen in the trial is to serve as a standard-of-care therapy, providing a basis for comparison with the experimental treatment.

A placebo control is also utilized in the study, consisting of a saline solution, specifically a 0.9% sodium chloride solution for injection. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The administration of the placebo follows the same route as the experimental and comparator treatments, ensuring consistency in the study design.

The efficacy of **nipocalimab** in the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the time to the first occurrence of a relapse event, defined by the deterioration in the adjusted INCAT disability score relative to Stage B baseline or the switch to intravenous immunoglobulin (IVIg) or other standard of care (SoC) due to investigator-assessed lack of efficacy, confirmed by an independent Relapse Adjudication Committee (RAC).

Secondary endpoints include various measures of clinical response and functional improvement. These encompass the time to initial confirmed ECI, percentage of responders as determined by ECI, and changes from Stage A baseline over time in adjusted INCAT disability score, MRC Muscle Grading Scale Sum score, I-RODS centile score, and mean grip strength for both dominant and non-dominant hands. Additionally, the time to first adjusted INCAT disability score deterioration and the time to first switch to IVIg or other SoC relative to Stage B baseline will be evaluated. A binary response endpoint will also be assessed, requiring improvement in adjusted INCAT disability score, absence of relapse, no switch to SoC, and no discontinuation of treatment.

Further assessments include the percentage of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ECG, vital signs, and clinical laboratory values over time, and the incidence of clinically significant abnormalities in these parameters. The study will also monitor the percentage of participants with suicidal ideation or behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS), serum **nipocalimab** concentrations over time, incidence and titers of anti-drug antibodies (ADA) to **nipocalimab**, presence of neutralizing antibodies (NAb) to **nipocalimab**, and changes in total serum IgG concentrations over time.