Giant Cell Arteritis and Anakinra Trial

NCT02902731 | Terminated Phase 3 DMC

• 1 other identifier: 2015-005804-27 N° CHU : 15-200
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Giant Cell Arteritis

Outcome Measures

Primary Outcomes (1)

• global relapse rate

  Week 26

Secondary Outcomes (7)

• specific relapse rate

  Week 4 to Week 16

• specific relapse rate

  Week 17 to Week 26

• specific relapse rate

  W27 to W52

• speed efficiency : time of obtaining a complete remission over a follow up of 52 weeks period

  baseline up to 52 weeks

• number of first relapse

  baseline up to 52 weeks

Other Outcomes (3)

• T-cells (Th1, Th2, Th17 et Treg) et T CD8 (Tc1, Tc2, Tc17)

  at Week 0, Week 16

• Cytokines (IL-6, IL-17, IFN-γ, IL-1β et TNF-α)

  at Week 0, Week 16

• vascular smooth muscles, fibroblastes (cytokines, inflammasome)

  at Week 0, Week 16

Study Arms (2)

placebo

PLACEBO COMPARATOR

PLACEBO + Usual use of tapering doses of oral prednisone

Drug: PLACEBO

anakinra

EXPERIMENTAL

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.

Drug: ANAKINRA

Interventions

PLACEBO DRUG

subcutaneous injection of placebo every day during 16 weeks

Also known as: comparative drug

placebo

ANAKINRA DRUG

subcutaneous injection of anakinra every day during 16 weeks

anakinra

Eligibility Criteria

• Age: 51 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years
• Patient with temporal arteritis giant cell match 3 of the 5 criteria of the American College of Rheumatology (ACR) that:
• Given a temporal artery biopsy compatible with a diagnosis of GCA (not necrotizing arteritis, giant cell with a granulomatous inflammatory infiltrate, usually localized to the intima-media junction, makes lymphocytes, macrophages and multinucleated giant cells; or minimum detection of a chronic inflammatory infiltrate fact lymphocytes and some neutrophils or eosinophils without giant cells).
• Either abdominal thoracic aortitis diagnosed by:
• Angio CT: circumferential thickening of the aortic wall more than 3 mm, in the absence of adjacent plaque and active infection.
• MR angiography: wall thickening of the aortic wall with hyperintense on T1 weighted and T2 weighted enhancement after gadolinium injection.
• PET scanner: increased uptake of FDG by the aorta and its branches is not typical for GCA and may be in the atheroma. The PET scanner is probably a very sensitive technique but not specific enough to retain the diagnosis of GCA. We therefore consider the PET CT as a diagnostic method of secondary aortite the GCA if there simultaneously on the same exam fixing aortic (thoracic or abdominal) and blood of large caliber (artery (s) axillary ( s), subclavian (s) and / or carotid (s) of FDG.
• Newly diagnosed disease and from corticosteroid started up to 14 days, the initial dose is less or equal to1 mg / Kg or
• GCA recurrence of continuous therapy with corticosteroids (including hydroprednisone) and / or immunosuppression was stopped for at least 6 months. At the time of recurrence, at least 3 of 5 ACR criteria for the diagnosis of GCA must be present. Furthermore :
• if BAT (Biopsy of the temporal artery) was positive at the time of initial diagnosis, it is not necessary to make a new.
• if BAT was negative, the patient can not be included after completion of a new BAT which will be positive or if there is a aortite, evidenced by angio-CT or MR angiography or PET scanner.
• For men and women of childbearing age, effective contraception must be used in the patient or his partner for the duration of treatment with anakinra (or placebo) and for 3 months after treatment. Also, breastfeeding is allowed after 3 months of stopping anakinra. Women considered not at risk of pregnancy are defined with menopause for at least a year or surgically sterile (tubal ligation, bilateral oophorectomy or hysterectomy)
• Patient wo has given its written consent Patient affiliated with a social security

You may not qualify if:

• pathologies, habitus or other patient characteristics
• Pregnancy, breastfeeding women or women of childbearing potential not using contraception
• dementia syndrome
• Patient not observing
• Patients who live more than 150 km from the investigation center
• ethyl or drug intoxication history that required hospitalization in the previous year
• Patient monitoring and / or treated to another autoimmune disease or known inflammatory
• Hypersensitivity to anakinra or any of its excipients (Sodium citrate (E331), sodium chloride, disodium edetate (E385), polysorbate 80 (E433), sodium hydroxide (E524), water for injections, substrates of origin: Escherichia coli proteins)
• Person under judicial protection, guardianship
• Person deprived of liberty
• Person not beneficiaries of the social security system
• Other therapeutic
• \- Patient has already started (or stopped there less than 6 months) in a protocol or not frame to its ACG or another disease, treatment with anti TNF-alpha, methotrexate, cyclosporine, cyclophosphamide, dapsone or bolus corticosteroids.
• Patients on long-term glucocorticoid for another condition
• Early treatment of CAG disease with a dose\> 1 mg / kg whatever the duration

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

Pr Aouba

Caen, 14000, France

Location

Related Publications (2)

• de Boysson H, Ly KH, Geffray L, Quemeneur T, Liozon E, Bezanahary H, Gouellec NL, Audemard A, Dumont A, Deshayes S, Boutemy J, Maigne G, Martin Silva N, Sultan A, Le Mauff B, Petit G, Parienti JJ, Aouba A. Four months of treatment with anakinra combined with glucocorticoids for giant cell arteritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Res Ther. 2025 Jun 7;27(1):122. doi: 10.1186/s13075-025-03493-z.

  PMID: 40483523 RESULT

• Sun MM, Pope JE. Polymyalgia rheumatica and giant cell arteritis: diagnosis and management. Curr Opin Rheumatol. 2025 Jan 1;37(1):32-38. doi: 10.1097/BOR.0000000000001059. Epub 2024 Oct 14.

  PMID: 39400109 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Achille AOUBA, MD PHD

  CHU CAEN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2016
• First Posted: September 16, 2016
• Study Start: May 11, 2017
• Primary Completion: November 25, 2022
• Study Completion: November 25, 2022
• Last Updated: April 2, 2026

Record last verified: 2023-02

Locations

FR (1)