Phase IIa Double-Blind, Randomized, Placebo-Controlled Study of CIT-013 on Disease Activity in Moderately Active Rheumatoid Arthritis Patients

The primary objective of this trial is to evaluate the **efficacy** of CIT-013 in patients with moderately active rheumatoid arthritis (RA). This is clinically relevant as it aims to determine the therapeutic potential of CIT-013 in managing disease activity in this patient population, potentially offering a new treatment option.

Secondary objectives include:

• Describing the safety and tolerability of CIT-013 in patients with moderately active RA.
• Evaluating the efficacy of CIT-013 per dose level in patients with moderately active RA.
• Assessing the effect of CIT-013 on disease activity in patients with moderately active RA.
• Evaluating the effect of CIT-013 on patient-reported health assessments in patients with moderately active RA.
• Characterizing the pharmacokinetic profile of CIT-013 in patients with moderately active RA.

The clinical trial involves participants diagnosed with **Moderately Active Rheumatoid Arthritis**. The study population includes both male and female subjects, aged 18 years and older, who meet the 2010 classification criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) for rheumatoid arthritis. Participants must have a Disease Activity Score of 3.2 or higher, with at least three swollen and three tender joints, and elevated CRP/ESR levels. They are required to be stable on a conventional synthetic disease-modifying antirheumatic drug (csDMARD) for at least four weeks prior to the trial. The trial does not include a vulnerable population. Participants must have a body mass index between 18 and 35 kg/m². Lifestyle considerations include the use of adequate contraception for both male and female participants, with specific guidelines for women of childbearing potential and restrictions on donating ova or sperm during and after the trial. The sponsor has not provided information on the total number of participants in the study.

The clinical trial is a **Phase IIa**, double-blind, randomized, parallel-arm, placebo-controlled study designed to evaluate the efficacy of CIT-013 in patients with moderately active **rheumatoid arthritis**. The trial involves three dose levels of CIT-013 and aims to assess the mean change in DAS28-CRP from baseline to day 43 as the primary endpoint. The study is expected to commence recruitment on July 31, 2025, and conclude by November 30, 2026. Participants will be randomly assigned to receive either CIT-013 or a placebo, with the trial maintaining a double-blind design to ensure unbiased results.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease activity score, and stability on a conventional synthetic disease-modifying antirheumatic drug. The trial will include follow-up visits to monitor treatment-emergent adverse events and assess secondary endpoints, such as changes in disease activity indices and pharmacokinetic levels. The end-of-study visit will evaluate the overall treatment efficacy and safety.

The expected duration of participant involvement is approximately 10 weeks, with the treatment period lasting up to 10 days. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial will ensure that all procedures are conducted in accordance with ethical guidelines and regulatory requirements, with informed consent obtained from all participants prior to enrollment.

The clinical trial involves the administration of two treatments, one of which is the experimental medication **CIT-013**. CIT-013 is a **concentrate for solution for infusion** and is administered via **subcutaneous injection**. The active substance, CIT-013, is of protein origin and is provided by CITRYLL B.V. The maximum daily dose of CIT-013 is 100 mg, with a total maximum dose of 600 mg over a treatment period of 10 days. The administration schedule is designed to ensure consistent dosing, and participant compliance is monitored throughout the trial to maintain the integrity of the study data.

The second treatment used in the trial is a non-experimental comparator, **0.9% w/v Sodium Chloride Injection BP**, which serves as a placebo. This solution for injection is administered subcutaneously and is provided by B.BRAUN MELSUNGEN AG. The maximum daily dose is 1 ml, with a total maximum dose of 6 ml over the same 10-day treatment period. The use of sodium chloride as a placebo allows for the assessment of the efficacy of CIT-013 in comparison to a standard inert substance. Compliance with the administration of the placebo is similarly monitored to ensure accurate and reliable results.

The efficacy of CIT-013 in patients with moderately active **Rheumatoid Arthritis** will be assessed using several parameters. The primary endpoint is the mean change in the Disease Activity Score 28 - C-reactive protein (DAS28-CRP) from baseline to day 43, comparing the pooled 50 mg and 100 mg CIT-013 treatment arms to placebo. Secondary endpoints include the frequency and severity of treatment-emergent adverse events (TEAEs) throughout the trial, mean changes in DAS28-CRP from baseline to days 43 and 85 per treatment arm, and the proportion of American College of Rheumatology (ACR) 20, ACR50, and ACR70 responders from baseline to days 43 and 85 per treatment arm. Additionally, the proportion of participants achieving low disease activity (DAS28-CRP ≤ 3.2) and disease remission (DAS28-CRP < 2.6) from baseline to days 43 and 85 will be evaluated.

Further assessments include mean changes in the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) scores from baseline to days 43 and 85, and mean changes in the Health Assessment Questionnaire Disability Index (HAQDI) scores from baseline to days 43 and 85. Pharmacokinetic levels will also be monitored throughout the trial per treatment arm. These efficacy parameters will be measured and collected at specified timepoints using validated scales and laboratory tests, ensuring a comprehensive evaluation of CIT-013's impact on disease activity in the study population.