A Study of RoActemra/Actemra (Tocilizumab) in Patients With Giant Cell Arteritis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01791153
First received: February 12, 2013
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

This multicenter, randomized, double-blind, placebo-controlled study will evalua te the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with g iant cell arteritis. Patients will be randomized to receive either RoActemra/Act emra 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 w ill stop study treatment and enter long-term follow-up, whereas patients with di sease activity or flares will receive open-label RoActemra/Actemra 162 mg subcut aneously weekly for a maximum period of 104 weeks at the discretion of the inves tigator. Anticipated time on study is 39 months.


Condition Intervention Phase
Giant Cell Arteritis
Drug: prednisone
Drug: prednisone placebo
Drug: tocilizumab [RoActemra/Actemra]
Drug: tocilizumab placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Total cumulative prednisone dose (TCZ + 26 weeks prednisone taper versus placebo + 26 and 52 weeks prednisone taper) [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the concentration-time curve (AUC) of tocilizumab in combination with 26 week tapering prednisone [ Time Frame: up to Week 52 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Tocilizumab concentrations in combination with 26 week tapering prednisone (Cmin, Cmax, Ctrough) [ Time Frame: up to Week 52 ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Interleukin 6/sIL-6R/ESR/CRP [ Time Frame: up to Week 52 ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]
  • Incidence of anti-tocilizumab antibodies [ Time Frame: approximately 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: July 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 2: open-label TCZ qw Drug: tocilizumab [RoActemra/Actemra]
162 mg SC qw, 104 weeks
Placebo Comparator: Placebo + 26 wks prednisone taper Drug: prednisone
tapering doses orally daily
Drug: prednisone placebo
incremental doses orally daily
Drug: tocilizumab placebo
matching SC placebo, 52 weeks
Placebo Comparator: Placebo + 52 wks prednisone taper Drug: prednisone
tapering doses orally daily
Drug: prednisone placebo
incremental doses orally daily
Drug: tocilizumab placebo
matching SC placebo, 52 weeks
Experimental: TCZ q2w + 26 wks prednisone taper Drug: prednisone
tapering doses orally daily
Drug: prednisone placebo
incremental doses orally daily
Drug: tocilizumab [RoActemra/Actemra]
162 mg SC every other week (q2w), 52 weeks
Experimental: TCZ qw +26 wks prednisone taper Drug: prednisone
tapering doses orally daily
Drug: prednisone placebo
incremental doses orally daily
Drug: tocilizumab [RoActemra/Actemra]
162 mg subcutaneous (SC) every week (qw), 52 weeks

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01791153

Contacts
Contact: Reference Study ID Number: WA28119 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Show 103 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01791153     History of Changes
Other Study ID Numbers: WA28119, 2011-006022-25
Study First Received: February 12, 2013
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arteritis
Giant Cell Arteritis
Polymyalgia Rheumatica
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 18, 2014