A Multicenter Randomized Placebo-Controlled Study of Leflunomide for Relapse Prevention in Polymyalgia Rheumatica During Corticosteroid Tapering

The primary objective of this study is to evaluate whether the administration of **leflunomide** can effectively prevent relapses during the tapering of corticosteroids in patients diagnosed with **polymyalgia rheumatica**. This is clinically significant as it aims to address the challenge of managing disease activity while reducing corticosteroid dependency, which is associated with numerous adverse effects.

The clinical trial focuses on patients diagnosed with **polymyalgia rheumatica**. The study population includes both male and female participants aged 50 years and older. Participants are required to meet the American College of Rheumatology/European League Against Rheumatism 2012 PMR core classification criteria and must be newly diagnosed, having been on corticosteroids for less than four weeks. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that the study population is representative of individuals who are in the early stages of treatment for polymyalgia rheumatica, allowing for the investigation of leflunomide's efficacy in preventing relapses during corticosteroid tapering.

The clinical trial is designed to evaluate the efficacy of **leflunomide** in preventing relapses during corticosteroid tapering in patients with **polymyalgia rheumatica**. This is a multicenter, randomized, double-blind, placebo-controlled study. Participants will be randomly assigned to receive either leflunomide or a placebo, both administered orally in the form of film-coated tablets. The trial is expected to span a duration of approximately 10 years, with an estimated recruitment start date of April 1, 2018, and an estimated end date of April 1, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥ 50 years) and a recent diagnosis of polymyalgia rheumatica. Following successful screening, participants will be enrolled and randomized into the treatment or placebo group. The primary endpoint is the time to the first relapse at 12 months. Study visits will include regular follow-up assessments to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the conclusion of the treatment period, or earlier if the participant experiences a relapse or meets any criteria for early termination.

The expected length of participant involvement in the study is up to 104 weeks for those receiving leflunomide and up to 52 weeks for those receiving the placebo. Conditions that may lead to early termination from the study include significant adverse reactions, non-compliance with the study protocol, or withdrawal of consent by the participant. The study aims to provide valuable insights into the management of polymyalgia rheumatica and the potential role of leflunomide in reducing relapse rates during corticosteroid tapering.

The clinical trial involves the administration of **Leflunomide**, marketed as Leflunomide Mylan 10 mg, film-coated tablets. This experimental medication is formulated as a film-coated tablet and is administered orally. The active substance, **leflunomide**, is of chemical origin. The maximum daily dose is 20 mg, with a total maximum dose of 14,600 mg over a treatment period of 104 weeks. For the purposes of this trial, the tablets will be over-encapsulated in blue opaque oblong-shaped capsules, size 0, to maintain blinding. The primary objective of the trial is to assess the efficacy of leflunomide in preventing relapses during corticosteroid tapering in patients with polymyalgia rheumatica.

The study also includes a **placebo** as a comparator treatment. The placebo is similarly formulated as a film-coated tablet and is administered orally. It contains no active pharmaceutical ingredient and serves as a control to evaluate the efficacy of the experimental treatment. The placebo tablets will also be over-encapsulated in blue opaque oblong-shaped capsules, size 0, to ensure blinding. The placebo group will follow a treatment period of 52 weeks. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the time to the first relapse at 12 months. The trial aims to determine whether the use of **leflunomide** can prevent relapses during corticosteroid tapering in patients with polymyalgia rheumatica. The study is designed as a multicenter, randomized, placebo-controlled treatment study. Participants will be administered either **leflunomide** or a placebo, both over-encapsulated in blue opaque oblong-shaped capsules, and taken orally. The maximum treatment period for **leflunomide** is 104 weeks, while the placebo is administered for up to 52 weeks. The efficacy assessments will be conducted at specified intervals throughout the trial duration, with the primary focus on the 12-month mark to determine the time to the first relapse. Data collection and analysis will be performed in accordance with the trial protocol to ensure the reliability and validity of the results.