Long-Term Extension Study of RO7790121 (Afimkibart) for Safety and Efficacy in Adults with Moderate-to-Severe Rheumatoid Arthritis

The primary objective is to assess the long-term safety and tolerability of afimkibart in participants with moderate to severe rheumatoid arthritis, providing data on chronic exposure risk and informing risk–benefit assessment for continued therapy. Secondary objectives include:

• Evaluation of the long-term efficacy of afimkibart, measured by sustained clinical response and disease activity reduction.
• Assessment of the overall safety profile, encompassing adverse event incidence and laboratory safety markers.
• Characterization of the drug’s Pharmacokinetics to define exposure parameters during extended treatment.

Seventy‑four participants, comprising both female and male adults, were enrolled in the extension phase. All subjects had a diagnosis of moderate to severe rheumatoid arthritis (RA) and had completed the treatment period of the preceding parent study. Enrollment required continuation in the follow‑up visit, adherence to contraception requirements, and achievement of at least a 20 % improvement in swollen or tender joint counts relative to baseline. The cohort included individuals classified as vulnerable, reflecting inclusion of patients who might otherwise be under‑represented. No specific dietary, physical‑activity, or habit restrictions were stipulated in the protocol.

The study is a Phase 4 extension trial evaluating the long‑term safety and tolerability of afimkibart in participants with moderate to severe rheumatoid arthritis who have completed a prior afimkibart clinical trial; eligibility requires completion of the parent study treatment period, adherence to contraception requirements, and ≥20 % improvement in swollen and tender joint counts at the parent study follow‑up visit. After a screening visit to confirm eligibility, subjects receive baseline assessments and are assigned to receive either the investigational product or matching placebo (RO7790121) by subcutaneous injection according to the randomization scheme of the parent study; subsequent scheduled follow‑up visits occur at predefined intervals to monitor safety, efficacy, laboratory values, vital signs, and serum drug concentrations, culminating in an end‑of‑study visit. The overall trial duration is projected from June 2026 to July 2033, with each participant remaining in the study for the full extension period unless early termination criteria are met, such as serious adverse events, discontinuation due to toxicity, significant protocol violations, or investigator‑determined lack of clinical benefit. The primary endpoint is the incidence and severity of adverse events, including serious events, discontinuations, and events of special interest, while the secondary endpoints include ACR20/50/70 response rates, changes in DAS28‑CRP, achievement of low disease activity or remission by DAS28‑CRP, DAS28‑ESR, CDAI, or SDAI, and changes in selected laboratory and vital sign parameters.

The investigational product, Afimkibart (RO7790121), is supplied as a solution for injection/infusion for subcutaneous administration. The preparation is presented in a dosage form described as “0 DF dosage form,” and is administered by subcutaneous injection. Dosing frequency follows the protocol‑specified schedule, with each dose administered at the designated study visit. Compliance with the injection regimen is monitored through site‑maintained administration logs and verification of returned study material.

The control arm utilizes a matching placebo identified as RO7790121. The placebo is categorized as “N/A” for pharmaceutical form, with no active substance and no specified dose or route. It is administered in a manner that mirrors the subcutaneous injection schedule of the active product to preserve blinding. Placebo administration is similarly tracked using study‑wide injection logs to ensure adherence to the dosing timetable.

All participants in the extension study have a diagnosis of rheumatoid arthritis and were previously enrolled in afimkibart clinical trials. Standard‑of‑care therapies permitted by the protocol may be continued concurrently, provided they do not interfere with the study medication or placebo administration.

Efficacy will be evaluated using a set of secondary endpoints that include the proportion of participants achieving American College of Rheumatology ACR20, ACR50, and ACR70 responses, the change from baseline in DAS28‑CRP, and the proportion of participants attaining Low Disease Activity (LDA) or Clinical Remission (CR) as defined by DAS28‑CRP, DAS28‑ESR, CDAI, or SDAI. Additional efficacy‑related assessments comprise changes from baseline in selected clinical laboratory test results, vital signs, and the serum concentration of afimbikart at predefined timepoints.

Response assessments will be performed using validated instruments and criteria, such as the ACR response criteria and the DAS28 composite scores, with baseline values derived from the parent study. Measurements will be obtained at scheduled visits throughout the extension period. Collected data will be analyzed using descriptive statistics and appropriate inferential methods to compare changes from baseline and to determine the proportion of participants meeting each response threshold.