Overview

This trial is active, not recruiting.

Condition giant cell arteritis
Treatments prednisone, prednisone placebo, tocilizumab [roactemra/actemra], tocilizumab placebo
Phase phase 3
Sponsor Hoffmann-La Roche
Start date July 2013
End date April 2018
Trial size 226 participants
Trial identifier NCT01791153, 2011-006022-25, WA28119

Summary

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with giant cell arteritis. Patients will be randomized to receive either RoActemra/Actemra 162 mg subcutaneously weekly or every 2 weeks or placebo for 52 weeks, with tapering oral daily doses of prednisone. After Week 52, patients in remission will stop study treatment and enter long-term follow-up, whereas patients with disease activity or flares will receive open-label RoActemra/Actemra 162 mg subcutaneously weekly for a maximum period of 104 weeks at the discretion of the investigator. Anticipated time on study is 39 months.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
tocilizumab [roactemra/actemra]
162 mg SC qw, 104 weeks
(Placebo Comparator)
prednisone
tapering doses orally daily
prednisone placebo
incremental doses orally daily
tocilizumab placebo
matching SC placebo, 52 weeks
(Placebo Comparator)
prednisone
tapering doses orally daily
prednisone placebo
incremental doses orally daily
tocilizumab placebo
matching SC placebo, 52 weeks
(Experimental)
prednisone
tapering doses orally daily
prednisone placebo
incremental doses orally daily
tocilizumab [roactemra/actemra]
162 mg SC every other week (q2w), 52 weeks
(Experimental)
prednisone
tapering doses orally daily
prednisone placebo
incremental doses orally daily
tocilizumab [roactemra/actemra]
162 mg subcutaneous (SC) every week (qw), 52 weeks

Primary Outcomes

Measure
Proportion of patients in sustained remission at Week 52 (TCZ + 26 weeks prednisone taper versus placebo + 26 weeks prednisone taper)
time frame: approximately 2 years

Secondary Outcomes

Measure
Proportion of patients in sustained remission at Week 52 (TCZ + 26 weeks prednisone taper versus placebo + 52 weeks prednisone taper)
time frame: approximately 2 years
Time to giant cell arteritis disease flare after clinical remission (TCZ + 26 weeks prednisone taper versus placebo + 26 and 52 weeks prednisone taper)
time frame: approximately 2 years
Total cumulative prednisone dose (TCZ + 26 weeks prednisone taper versus placebo + 26 and 52 weeks prednisone taper)
time frame: approximately 2 years
Patient reported outcome: Short form SF-36 questionnaire (TCZ + 26 weeks prednisone taper versus placebo + 26 and 52 weeks prednisone taper)
time frame: approximately 2 years
Patient reported outcome: Patient global assessment (PGA) of disease activity on visual analogue scale (VAS) (TCZ + 26 weeks prednisone taper versus placebo + 26 and 52 weeks prednisone taper)
time frame: approximately 2 years
Pharmacokinetics: Area under the concentration-time curve (AUC) of tocilizumab in combination with 26 week tapering prednisone
time frame: up to Week 52
Pharmacokinetics: Tocilizumab concentrations in combination with 26 week tapering prednisone (Cmin, Cmax, Ctrough)
time frame: up to Week 52
Pharmacodynamics: Interleukin 6/sIL-6R/ESR/CRP
time frame: up to Week 52
Safety: Incidence of adverse events
time frame: approximately 4 years
Incidence of anti-tocilizumab antibodies
time frame: approximately 4 years

Eligibility Criteria

Male or female participants at least 50 years old.

Inclusion Criteria: - Diagnosis of giant cell arteritis classified according to the following criteria: - Age >/= 50 years - History of ESR >/= 50 mm/hour - and at least one of the following: - Unequivocal cranial symptoms of giant cell arteritis - Symptoms of polymyalgia rheumatica - and at least one of the following - Temporal artery biopsy revealing features of giant cell arteritis - Evidence of large-vessel vasculitis - New onset active disease (diagnosis within 6 weeks of baseline) or refractory active disease (diagnosis > 6 weeks before baseline and previous treatment with >/= 40 mg/day prednisone (or equivalent) for at least 2 consecutive weeks at any time); active disease defined as presence of clinical signs and symptoms and ESR >/= 30 mm/hour or CRP >/= 1 mg/dl within 6 weeks of baseline Exclusion Criteria: - Recent or incoming major surgery - Organ transplantation recipient (except corneas within 3 months prior to baseline visit) - Major ischemic event, unrelated to giant cell arteritis, within 12 weeks of screening - Prior treatment with any of the following: - Investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening visit - Cell-depleting agents (e.g. anti CD 20) - Tocilizumab - Tofacitinib - Alkylating agents including CYC within 6 months of baseline - HCQ, CsA, AZA, or MMF within 4 weeks of baseline - Tumor necrosis factor inhibitors within 2-8 weeks of baseline - Anakinra within 1 week of baseline - Corticosteroids for conditions other than GCA - IV corticosteroids within 6 weeks of baseline - History of severe allergic reactions to monoclonal antibodies - Evidence of serious uncontrolled concomitant disease (e.g. cardiovascular, respiratory, renal, endocrine) - Current liver disease that could interfere with the trial as determined by the investigator - History of diverticulitis, inflammatory bowel disease, or other symptomatic GI tract condition that might predispose to bowel perforation - Infections: - Active current or history of recurrent bacterial, viral fungal, mycobacterial, or other infection - Prior episode of major infection - Active TB requiring treatment within the previous 3 years - Untreated latent TB infection (LTBI) - Primary or secondary immunodeficiency - Malignancy (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured) - Inadequate hematologic, renal or liver function - Positive for hepatitis B or hepatitis C infection

Additional Information

Official title A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF TOCILIZUMAB IN SUBJECTS WITH GIANT CELL ARTERITIS
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.