Efficacy, Safety, and Tolerability of IMVT-1402 in ACPA-Positive Rheumatoid Arthritis: A Phase 2b Multicenter, Double-Blind, Placebo-Controlled Study

The primary objective of this Phase 2b, multicenter, double-blind, placebo-controlled randomized withdrawal study is to evaluate the effects of **IMVT-1402** in adult participants with active, difficult-to-treat, ACPA-positive **Rheumatoid Arthritis** (RA). The efficacy of IMVT-1402 will be assessed using the American College of Rheumatology 20% (ACR20) Response criteria. This measure is clinically relevant as it provides a standardized method to evaluate the improvement in RA symptoms, which is crucial for determining the therapeutic potential of the investigational drug. The study aims to provide insights into the safety and tolerability of IMVT-1402, administered as a solution for injection, in comparison to a placebo. The trial does not specify any secondary objectives.

The clinical trial involves a total of **123 participants** diagnosed with **ACPA-Positive Rheumatoid Arthritis**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a confirmed diagnosis of 'definite RA' according to the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria, and an inadequate response to at least two classes of biologic or targeted synthetic DMARDs. The trial does not include a vulnerable population. Participants' general health status is characterized by elevated C-reactive protein levels and elevated immunoglobulin G and ACPA at the screening visit. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and tolerability of **IMVT-1402** in adult participants with active, difficult-to-treat, ACPA-positive **rheumatoid arthritis**. The trial will involve a withdrawal phase and is categorized as a Phase 2b therapeutic exploratory and confirmatory trial. The study will commence with an estimated recruitment start date of June 15, 2025, and is projected to conclude by September 30, 2027. Participants will be randomly assigned to receive either the investigational medicinal product, IMVT-1402, administered as a **solution for injection** via **subcutaneous use**, or a placebo that is identical in appearance but contains no active substance.

The trial will span a maximum treatment period of 76 weeks, with a maximum daily dose of 600 mg and a total dose not exceeding 45,600 mg. The sequence of study visits includes an initial **screening visit** to confirm eligibility based on criteria such as a diagnosis of definite rheumatoid arthritis according to the 2010 ACR/EULAR Classification Criteria, specific joint counts, elevated C-reactive protein levels, and inadequate response to at least two classes of biologic or targeted synthetic DMARDs. Following the screening, participants will undergo a **baseline visit** to establish initial health metrics and commence treatment.

Subsequent **follow-up visits** will be scheduled at regular intervals to monitor the participants' response to treatment, assess safety parameters, and adjust dosages if necessary. The primary endpoint is the proportion of participants achieving an ACR20 response at Week 28. Secondary endpoints include changes in the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scores from Week 16 to Week 28. The trial will conclude with an **end-of-study visit** to evaluate the overall outcomes and gather final data.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide comprehensive data on the therapeutic potential of IMVT-1402 in managing ACPA-positive rheumatoid arthritis, contributing to the understanding of its clinical benefits and safety profile.

The clinical trial involves the administration of **IMVT-1402**, an investigational medicinal product developed by Immunovant Sciences GmbH. **IMVT-1402** is formulated as a **solution for injection** and is intended for **subcutaneous use**. The active substance, also named **IMVT-1402**, is classified as a protein of other origin. The maximum daily dose is set at 600 mg, with a total maximum dose of 45,600 mg over a treatment period of 76 days. The administration schedule and participant compliance will be closely monitored to ensure adherence to the dosing regimen.

The study also includes a **placebo** group, which receives an injection identical in appearance to the investigational product but contains no active substance. The 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. This approach allows for an unbiased assessment of the efficacy, safety, and tolerability of **IMVT-1402** in comparison to the placebo in participants with active, difficult-to-treat, ACPA-positive **rheumatoid arthritis**.

Efficacy in the clinical trial will be assessed using the **American College of Rheumatology 20% (ACR20) Response** as the primary endpoint. This will involve evaluating the proportion of participants who achieve an ACR20 response at Week 28. Secondary endpoints include changes in the Clinical Disease Activity Index (CDAI) score and the Simplified Disease Activity Index (SDAI) score from Week 16 to Week 28. These assessments will provide a comprehensive evaluation of the treatment's impact on disease activity in participants with active, difficult-to-treat, ACPA-positive rheumatoid arthritis.