Clinical Trial: Giant Cell Arteritis and Anakinra Trial

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Randomized, Controlled, Double-blind Study of Anakinra Against Placebo in Addition to Steroids in Giant Cell Arteritis

Brief Summary:

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 pa

Detailed Summary:

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.


Sponsor: University Hospital, Caen

Current Primary Outcome: global relapse rate [ Time Frame: Week 26 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: University Hospital, Caen

Dates:
Date Received: July 5, 2016
Date Started: November 2016
Date Completion: March 2022
Last Updated: September 12, 2016
Last Verified: September 2016