Randomized Controlled Trial Comparing Fast and Slow Tapering Regimens of Prednisone in Patients with Giant Cell Arteritis

The primary objective of this study is to compare the rate of complete **remission** without any relapse in patients with **giant cell arteritis** (GCA) undergoing two different corticosteroid therapy regimens: a long regimen of 52 weeks versus a short regimen of 28 weeks, at week 52 (W52). The clinical relevance of this objective lies in verifying the non-inferiority of the shortened American scheme compared to the extended French and European scheme, which could potentially lead to a more efficient treatment protocol with reduced exposure to corticosteroids.

Secondary objectives include:

• The rates of 1st and 2nd relapses at weeks 28 (W28) and 52 (W52).
• The time limits for the 1st and 2nd relapses to occur.
• Cumulative doses of cortisone at W28 and W52.
• The levels of corticosteroid-dependent patients, defined as the inability to drop below 0.3 mg/kg at the end of the 6th month or 0.15 mg/kg at the end of the 12th month.
• Adverse effects attributable to corticosteroid therapy.

The clinical trial involves participants diagnosed with **giant cell arteritis** (GCA), also known as Horton’s disease. The study population includes both male and female subjects over the age of 50, with no specific vulnerability considerations noted. Participants were selected based on the presence of at least two of the four ACR 1990 bio-clinical criteria, which include age over 50 years, unusual headache, tenderness in the temporal artery pathway, or a biological inflammatory syndrome. Additionally, participants must have started oral corticosteroid therapy within the last 14 days, excluding boluses, and must be registered with the social security system. Written consent is required for participation. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized, controlled, open trial** to evaluate two standardized corticosteroid tapering regimens in patients with **giant cell arteritis**. The primary objective is to compare the rate of complete remission without relapse between a long regimen of 52 weeks and a short regimen of 28 weeks, with the hypothesis that the shorter regimen is non-inferior to the longer one. The trial is expected to conclude by January 1, 2032, with recruitment having commenced on May 3, 2021.

Participants will be involved in the study for a maximum of 52 weeks, depending on the assigned treatment arm. The study includes several key visits: an initial **screening visit** to confirm eligibility based on criteria such as age over 50, diagnosis of giant cell arteritis, and recent initiation of oral corticosteroid therapy. Follow-up visits will occur at regular intervals to monitor the participants' health status, measure primary and secondary endpoints, and adjust treatment as necessary. The **end-of-study visit** will assess the final outcomes, including remission status and any adverse events.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or withdraw consent. The primary endpoint is the number of patients in complete remission without relapse at week 52. Secondary endpoints include the measurement of relapse rates, time to relapse, and various health parameters such as blood pressure and glycemic control. The study will also monitor for complications related to corticosteroid therapy, including bone density changes and cardiovascular events.

The clinical trial involves the administration of **PREDNISONE**, a corticosteroid, in various dosages to evaluate its efficacy in the treatment of **giant cell arteritis**. The experimental medication, **PREDNISONE VIATRIS 1 mg**, is provided in tablet form. The active substance, prednisone, is of chemical origin. The maximum daily dose is 20 mg, and the treatment period extends up to 52 weeks. The route of administration is ocular use, and the medication is not formulated for pediatric use. Compliance with the dosing schedule is monitored throughout the trial.

Another experimental medication used in the trial is **PREDNISONE VIATRIS 5 mg**, also in tablet form. This formulation is a scored tablet, allowing for flexible dosing adjustments. The active substance remains prednisone, with a chemical origin. The maximum daily dose is consistent at 20 mg, with a treatment duration of up to 52 weeks. The administration route is ocular, and the formulation is not intended for pediatric patients. Participant adherence to the dosing regimen is closely monitored.

The trial also includes **PREDNISONE VIATRIS 20 mg**, provided as a scored tablet. The active ingredient is prednisone, chemically derived. The maximum allowable daily dose is 20 mg, with a treatment period of up to 52 weeks. The route of administration is ocular use, and the formulation is not suitable for pediatric populations. Monitoring of participant compliance with the dosing schedule is an integral part of the study protocol.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The study aims to compare the efficacy of two corticosteroid therapy regimens, with a focus on achieving complete remission without relapse in patients with giant cell arteritis.

Efficacy in the clinical trial will be assessed by evaluating the rate of complete remission without any relapse in patients with **giant cell arteritis** (GCA) at week 52 (W52). The primary endpoint is the number of patients in complete remission without relapse at W52 in each of the two arms of corticosteroid therapy: a long regimen of 52 weeks and a short regimen of 28 weeks. Secondary endpoints include the measurement of the number of first and second relapses at weeks 28 and 52, as well as the extremes, means, and medians of time to first and second relapses. Additionally, the study will measure the extremes, means, and medians of durations and individual cumulative doses of cortisone relative to body weights at weeks 28 and 52.

Further assessments will include the number of patients with cortico-dependent disease at W52, and various health parameters such as blood pressure, weight, glycemia, glycated hemoglobin, biochemistry, and complications related to infections, fractures, glaucoma, and cataracts. The trial will also screen for the onset or decompensation of type 2 diabetes and any cardiovascular events. Bone densitometry will be conducted at baseline, week 28, and week 52. Adverse events attributable to corticosteroid therapy will be monitored from the time consent is signed and throughout the study duration. These efficacy parameters will be collected and analyzed at specified timepoints to determine the non-inferiority of the shortened American scheme compared to the extended French and European scheme.