Giant Cell Arteritis and Anakinra Trial (GiAnT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02902731|
Recruitment Status : Not yet recruiting
First Posted : September 16, 2016
Last Update Posted : September 16, 2016
SYNOPSIS The giant cell arteritis (GCA) is the most frequent vasculitis in people over 50 years. Despite recent progress and physiopathogenic, corticosteroids remains the standard treatment for decades with a very good initial clinical efficacy but a high relapse rate (nearly 40% to 6,5 months) during its decay. This sensible population is particularly exposed to the side effects of corticosteroids, leading to think about savings strategies. But the association of immunosuppressive therapy and/or anti- TNFα has not demonstrated benefits in terms of efficiency or long-term tolerance to cumulative doses of prednisone. The responsibility of proinflammatory cytokines such as TNFα, IL- 6 and IL-1 has been studied in the pathogenesis of GCA in temporal artery walls and in mouse models. The primary pathogenic role of IL- 1 is based on the increase in serum or nuclear protein itself or that of its mRNA. The study of temporal artery biopsies has shown increased local production of IL- 1β mRNA, IL- 6 and TGFβ (indicative of macrophage activation ) and those of INFɣ and IL 2 (indicative of T lymphocyte activation). Recently, Ly et al (Ly KH JBS 2014) reported the efficacy of anakinra, a recombinant molecule of IL- 1RA specifically blocking the IL- 1 α/β, in three cases GCA refractory to conventional treatments.
Here investigators propose a randomized, multicenter, controlled, double-blind study of anakinra against placebo in addition to corticosteroids in the treatment of GCA.
This study will include 70 patients randomized equally in both arms: reference treatment (prednisone plus placebo) or the experimental treatment (prednisone + anakinra). Treatment with prednisone will be identical in the two arms, namely a dose of 0.7 mg/kg/day orally on day 1, followed by a progressive decrease in the dose pattern depending on the weight. In the experimental arm, dose of anakinra is the one usually used, ie 100 mg/day by subcutaneous injection from day 1 until the end of week 16 (S16). In the reference arm of the treatment, a placebo anakinra is associated with corticosteroid in the same packaging, duration and respecting the double-blind.
Investigators thus hypothesized that the addition of anakinra to corticosteroid compared to placebo added to the latter, will show a significant decrease in GAC relapse rate. Indeed, the challenge of corticosteroid therapy in this disease is not so much a problem of initial effectiveness, than the adverse events related to relapses and steroid dependence.
|Condition or disease||Intervention/treatment||Phase|
|Giant Cell Arteritis||Drug: PLACEBO Drug: ANAKINRA||Phase 3|
Side assumptions investigators made are that the patients receiving anakinra in add-on therapy will have: a time and a complete remission rate respectively shorter and higher, fewer relapses and a decrease of the total consumption of prednisone over a 12- month follow-up.
This controlled study is the first to assess the inhibition of the IL- 1 pathway in the GCA with anakinra in add-on therapy with corticosteroids in patients newly diagnosed or on relapse. The purpose of this work is to support the following proof of concept of the addition of anakinra to corticosteroid therapy in the treatment of GCA: potential synergies of this association and intrinsic therapeutic action of anakinra in patient newly diagnosed, and this without loss of opportunity for patients that will benefit all of the reference treatment. The other originality of this study is to demonstrate the steroid-sparing effect of targeting interleukin -1, which is per se a therapeutic and nosologic innovation for this disease. Finally, ancillary biological studies will clarify the mode of action of the anti-cytokine therapy and identify markers of response to this biotherapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Randomized, Controlled, Double-blind Study of Anakinra Against Placebo in Addition to Steroids in Giant Cell Arteritis|
|Study Start Date :||November 2016|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||March 2022|
Placebo Comparator: placebo
PLACEBO + Usual use of tapering doses of oral prednisone
Other Name: comparative drug
ANAKINRA : dose of anakinra is 100 mg/day by subcutaneous injection from day 1 until the end of week 16 (W16). The dose of Anakinra will be adapted to that recommand according to renal function.
Intervention Anakinra in add on Therapy.
- global relapse rate [ Time Frame: Week 26 ]
- specific relapse rate [ Time Frame: Week 4 to Week 16 ]
- specific relapse rate [ Time Frame: Week 17 to Week 26 ]
- specific relapse rate [ Time Frame: W27 to W52 ]
- speed efficiency : time of obtaining a complete remission over a follow up of 52 weeks period [ Time Frame: baseline up to 52 weeks ]
- number of first relapse [ Time Frame: baseline up to 52 weeks ]
- cumulative and the average dose of prednisone used [ Time Frame: baseline up to 52 weeks ]
- Safety according CTCAE v4.0 [ Time Frame: baseline up to 52 weeks ]
- T-cells (Th1, Th2, Th17 et Treg) et T CD8 (Tc1, Tc2, Tc17) [ Time Frame: at Week 0, Week 16 ]
- Cytokines (IL-6, IL-17, IFN-γ, IL-1β et TNF-α) [ Time Frame: at Week 0, Week 16 ]
- T-cells (Th1, Th2, Th17 et Treg) et T CD8 (Tc1, Tc2, Tc17)
- Cytokines (IL-6, IL-17, IFN-γ, IL-1β et TNF-α)
- vascular smooth muscles, fibroblastes (cytokines, inflammasome)
- vascular smooth muscles, fibroblastes (cytokines, inflammasome) [ Time Frame: at Week 0, Week 16 ]