Evaluation of Hydroxychloroquine with Leflunomide and Hydroxychloroquine with Mycophenolate Mofetil in Primary Sjögren's Syndrome: A Stratified Interventional Trial

The primary objective of this study is to evaluate the **efficacy** of each active treatment combination in patients with **Primary Sjogren's syndrome**. The combinations being assessed are hydroxychloroquine with leflunomide and hydroxychloroquine with mycophenolate mofetil. The efficacy will be determined based on the proportion of responder patients according to the preliminary STAR criteria at week 24 in the pooled cohorts. This is clinically relevant as it aims to identify effective treatment regimens for managing symptoms and improving the quality of life in patients with this chronic autoimmune condition.

The clinical trial involves participants diagnosed with **Primary Sjogren's syndrome**. 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. The trial does not focus on a vulnerable population. Participants were selected based on specific criteria, including the presence of symptoms and disease activity levels as defined by established criteria. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria include the requirement for participants to have given written informed consent and, for certain cohorts, to use highly reliable contraception during the study treatment and for two years after stopping treatment. The trial aims to evaluate the efficacy of treatment combinations in this patient population.

The clinical trial is designed to evaluate the efficacy of active treatment combinations in patients with **Primary Sjogren's syndrome**. This study is a **randomized, double-blind, controlled** trial involving two cohorts of patients. The trial will assess the efficacy of two treatment combinations: hydroxychloroquine with leflunomide and hydroxychloroquine with mycophenolate mofetil. The primary endpoint is the proportion of patients achieving a response according to preliminary STAR criteria at week 24. The trial is expected to run from April 2022 to January 2026, with a maximum treatment period of six months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as the ACR/EULAR 2016 or AECG 2002 criteria for **Primary Sjogren's syndrome**. The screening visit will also include a negative pregnancy test and confirmation of informed consent. Following randomization, participants will attend regular follow-up visits to monitor treatment efficacy and safety. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted.

The expected length of participant involvement is approximately six months, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with study protocols. Participants are required to use highly reliable contraception during the study and for two years after stopping treatment. The trial aims to provide valuable insights into the treatment of **Primary Sjogren's syndrome**, contributing to the development of effective therapeutic strategies.

The clinical trial involves the administration of several treatments, including both experimental medications and placebos. **Arava 20 mg film-coated tablets** contain the active substance **leflunomide**. These tablets are administered orally, with a maximum daily dose of 20 mg and a total maximum dose of 3600 mg over a treatment period of up to 6 months. The pharmaceutical form is a film-coated tablet, and the product is manufactured by Sanofi-Aventis Deutschland GmbH. Participant compliance with the dosing schedule will be monitored throughout the trial.

**Mycophenolate mofetil Teva 500 mg film-coated tablets** are another experimental treatment used in the trial. The active substance is **mycophenolate mofetil**, and the tablets are administered orally. The maximum daily dose is 2000 mg, with a total maximum dose of 360,000 mg over a 6-month treatment period. The tablets are produced by TEVA B.V. and are in the form of film-coated tablets. Compliance with the dosing regimen will be closely monitored.

**PLAQUENIL 200 mg, comprimé pelliculé** contains the active substance **hydroxychloroquine sulfate**. This medication is administered orally, with a maximum daily dose of 400 mg and a total maximum dose of 72,000 mg over a 6-month period. The pharmaceutical form is a film-coated tablet, and the product is manufactured by Sanofi Winthrop Industrie. Participant adherence to the dosing schedule will be assessed regularly.

The trial also includes the use of placebos to evaluate the efficacy of the active treatments. The **Placebo of leflunomide**, **Placebo of mycophenolate mofetil**, and **Placebo of hydroxychloroquine** are utilized as control treatments. These placebos do not contain active substances and are used to ensure the validity of the trial results by providing a baseline for comparison with the active treatments.

The efficacy of the clinical trial will be assessed by evaluating the proportion of responder patients according to the preliminary STAR criteria at week 24. The primary endpoint involves comparing the proportion of patients achieving a response between each active treatment arm and the placebo arm. The active treatment combinations being evaluated are hydroxychloroquine with leflunomide and hydroxychloroquine with mycophenolate mofetil. The trial focuses on patients with primary **Sjögren’s Syndrome** (pSS), and the efficacy assessment will be conducted in pooled cohorts. The assessment will be based on the response rates at the specified timepoint, which is week 24 of the trial.