Evaluation of Tocilizumab Discontinuation Strategies on Relapse-Free Survival in Patients with Giant Cell Arteritis
- Trial ID
- 2023-505515-21-00
- Protocol
- MAGICA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the efficacy of immediate versus gradual discontinuation of **tocilizumab** over 24 weeks on relapse-free survival in patients with **Giant Cell Arteritis** after 26 weeks of follow-up. This is clinically relevant as it aims to determine the optimal discontinuation strategy to maintain remission and minimize the risk of relapse, which is crucial for patient management and long-term outcomes.
Secondary objectives include:
- Comparing relapse-free survival at 52 and 78 weeks, corticosteroid use, quality of life, fatigue, and the proportion of patients in remission without prednisone at weeks 26, 52, and 78, as well as those in remission with a dose ≤5 mg/day of prednisone at the same time points.
- Identifying factors associated with the risk of relapse following the initiation of the discontinuation strategy, whether immediate or gradual.
- Assessing tolerance in both groups.
- Evaluating the frequency of steroid-related side effects in both groups.
- Conducting immunomonitoring to evaluate the effect of the discontinuation strategy on cytokine profile, T cell polarization, and IL-6 pathway activation.
- Evaluating the performance of 18 FDG PET scans in predicting the risk of relapse.
Participants
The clinical trial involves participants diagnosed with **Giant Cell Arteritis** (GCA), with an age range of 50 years and older. The study includes both male and female subjects, and the population is not considered vulnerable. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including a history of GCA in remission for at least 12 weeks prior to randomization and prior treatment with tocilizumab or its biosimilar. The trial does not focus on any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a stable health status, as indicated by recent biological workups showing good tolerance to tocilizumab and specific laboratory values within normal limits. The trial aims to assess the efficacy of immediate versus gradual discontinuation of tocilizumab over a 24-week period, with a follow-up at 26 weeks to evaluate relapse-free survival.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **tocilizumab** discontinuation strategies in patients with **Giant Cell Arteritis** (GCA). This is a randomized, double-blind, controlled trial with a primary objective to compare relapse-free survival between immediate and gradual discontinuation of tocilizumab over a 24-week period. The trial is expected to commence recruitment on January 1, 2024, and conclude by July 1, 2028. Participants will be involved in the study for a maximum of 78 weeks, with the primary endpoint assessed at 26 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits at weeks 12, 26, 52, and 78, and an end-of-study visit to assess final outcomes.
Inclusion criteria require participants to have a confirmed diagnosis of GCA, be in remission for at least 12 weeks prior to randomization, and have been treated with subcutaneous tocilizumab (162 mg/week) for at least 12 consecutive weeks. Exclusion criteria are not specified in the provided data. The trial will monitor primary endpoints such as relapse-free survival at 26 weeks, and secondary endpoints including cumulative prednisone dose, quality of life scores, and frequency of adverse events. Participants may be withdrawn from the study if they experience significant adverse events or if they do not adhere to the study protocol.
The trial will utilize **RoActemra** 162 mg solution for injection, administered via pre-filled syringe or pen, with a maximum treatment period of 24 weeks. The study aims to provide insights into the optimal discontinuation strategy for tocilizumab in maintaining remission in GCA patients, with a focus on minimizing relapse and improving quality of life. The trial will also explore factors associated with relapse-free survival and monitor immunological markers and imaging outcomes to predict relapse risk.
Treatment
The clinical trial involves the administration of **tocilizumab**, a monoclonal antibody targeting the interleukin-6 receptor, used in the treatment of **Giant Cell Arteritis**. The experimental medication is provided in two pharmaceutical forms: a solution for injection in a pre-filled syringe and a solution for injection in a pre-filled pen. Both forms contain 162 mg of tocilizumab and are administered via **subcutaneous injection**. The maximum daily dose is 162 mg, with a total treatment period of up to 24 weeks. The medication is manufactured by Roche Registration GmbH and is not a pediatric formulation. The administration schedule involves a single dose per week, and participant compliance is monitored through regular follow-up visits.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the efficacy of tocilizumab in preventing relapse in patients with Giant Cell Arteritis. The trial aims to compare the outcomes of immediate versus gradual discontinuation of tocilizumab over a 24-week period, with a follow-up at 26 weeks to assess relapse-free survival. Participants' adherence to the dosing schedule is crucial for the integrity of the trial results, and compliance is ensured through structured monitoring protocols.
Efficacy
The efficacy of the clinical trial titled "TocilizuMab discontinuAtion in GIant Cell Arteritis" will be assessed through a series of primary and secondary endpoints. The primary endpoint is the **relapse-free survival** in both groups (immediate vs. gradual discontinuation) at 26 weeks of follow-up. This is defined as the time from the start of the immediate or progressive discontinuation strategy to relapse or death from any cause, whichever occurs first.
Secondary endpoints include several measures: relapse-free survival at weeks 52 and 78, cumulative prednisone dose at weeks 26, 52, and 78, and quality of life scores (HAQ, SF-36) at weeks 0, 12, 26, 52, and 78. Additionally, the FACIT-Fatigue score will be evaluated at the same timepoints. The percentage of patients in remission without prednisone and those with a prednisone dose ≤5 mg/day will be assessed at weeks 26, 52, and 78. Factors associated with relapse-free survival, including demographic, clinical, and biological data related to Giant Cell Arteritis (GCA), will be analyzed at 26, 52, and 78 weeks of follow-up.
Adverse events and corticosteroid-related side effects will be monitored, with the frequency and type of adverse events recorded during the first 78 weeks. Immunomonitoring will involve measuring serum concentrations of specific biomarkers and the percentage of certain T cell subsets at specified timepoints and in case of relapse. Imaging assessments will include the calculation of the vascular score (PETVAS50) using an 18FDG PET scan to predict the risk of relapse at week 78. The PET scan will be performed between screening and randomization, with images sent for centralized review.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written consent
- Diagnosis of GCA, defined by the following criteria: Age ≥50 years at diagnosis
- Diagnosis of GCA, defined by the following criteria: History of ESR ≥50 mm/h OR CRP ≥20 mg/L (optional criterion if temporal artery biopsy (TAB) is positive).
- Diagnosis of GCA, defined by the following criteria: at least one of the following clinical criteria: -At least one unequivocal sign of GCA (recent headache, scalp hyperesthesia, jaw claudication, temporal artery abnormality, visual disturbances of ischemic origin) -Clinical sign(s) of polymyalgia rheumatica (PR)
- Diagnosis of GCA, defined by the following criteria: at least one of the following criteria during GCA follow-up: -TAB consistent with the diagnosis of GCA (non-necrotizing vasculitis with a mononuclear cell-rich inflammatory infiltrate or presence of granulomas, with or without multinuclear giant cells) -Evidence of temporal artery vasculitis by echo-Doppler of the temporal arteries (unilateral or bilateral halo sign) -Evidence of vasculitis of at least one large vessel by imaging (o angio-CT or angio-MRI: arterial wall thickening (≥2mm for aorta; ≥1mm for supra-aortic trunks and upper extremity arteries, ≥0.6mm for the cephalic artery, ...) and/or T1-weighted contrast. - o PET: grade 2 or 3* hypermetabolism of the wall of at least one large vessel (aorta, supra-aortic trunks, cephalic vessels, upper extremity arteries) (*i.e., arterial SUVmax ≥ liver SUVmax))
- GCA in remission for at least 12 weeks before randomisation (remission = absence of symptoms due to GCA AND CRP ≤10 mg/L)
- TCZ treatment (IV or SC) or biosimilar initiated 12 to 36 months prior to randomization
- TCZ treatment (IV or SC) or biosimilar not interrupted more than 12 weeks in the 12 months prior to randomization
- Treatment with subcutaneous TCZ (162 mg/week) or biosimilar for at least 12 consecutive weeks prior to randomization
- Treatment with corticoids stopped at least 12 weeks before randomization (hydrocortisone treatment ≤20 mg/day is possible if given at a stable dose for the duration of the study)
- Biological workup dating from less than 6 weeks on the day of randomization, showing good tolerance of tocilizumab: o AST and ALT < 1.5 x upper limit of normal (ULN) o Hemoglobin >8 g/dL o Platelets >100 G/L o Neutrophils >1 G/L o Lymphocytes >0.5 G/L
Exclusion Criteria
- Person who is not affiliated with the national health insurance system
- Recent or scheduled surgery within 6 months of randomization
- History of organ or hematopoietic marrow transplantation (except corneal transplantation performed at least 12 weeks prior to randomization)
- Primary or secondary immune deficiency
- Concomitant treatment with any of the following: - Methotrexate, leflunomide, cyclosporin A, azathioprine, mycophenolate mofetil, Janus kinase inhibitors, abatacept, secukinumab, anti-TNF-α, anakinra, ustekinumab, or any other immunosuppressive drug within 12 weeks prior to randomization - Rituximab or other anti-CD20 agent within 1 year prior to randomization - Cyclophosphamide in the year prior to randomization
- History of long-term corticosteroid therapy for conditions other than GCA or PPR. (NB: dermocorticoids, inhaled corticosteroids, and corticosteroid joint infiltrations are allowed during the study)
- Patient who has previously received ≥3 courses of oral corticosteroids for a disease other than GCA or RRP within 6 months prior to randomization
- Ongoing anti-tuberculosis treatment at the time of randomization
- Infections: - Current viral hepatitis B or C - Ongoing HIV infection - Severe infection requiring hospitalization within 30 days prior to randomization
- Any unstable or poorly controlled condition or disease, acute or chronic, not related to GCA, and considered a contraindication to tocilizumab therapy in the opinion of the investigator
- Person subject to a measure of legal protection (guardianship, tutorship)
- Neoplasia < 5 years, (except cervical cancer in situ and skin carcinoma, except melanoma, with R0 resection)
- Person subject to a court order
- Patient unable to give consent
- Person who does not speak French
- Pre-menopausal women (menopause = amenorrhea of more than 12 consecutive months)
- Uncontrolled psychotic state
- History of drug or alcohol intoxication requiring hospitalization within 12 months prior to randomization
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Jan 2024 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RoActemra 162 mg solution for injection in pre-filled syringe. | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 162 | 24 | PRD1576593 |
RoActemra 162 mg solution for injection in pre-filled pen. | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS INJECTION | 162 | 24 | PRD6143596 |