Study of Tocilizumab to Treat Polymyalgia Rheumatica

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Hospital for Special Surgery, New York
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Robert Spiera, MD, Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier:
NCT01396317
First received: July 11, 2011
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

This fifteen-month open label, Phase IIa clinical trial is being conducted to assess the tolerability, safety and efficacy of a medication called Tocilizumab (Actemra®) in patients with polymyalgia rheumatica (PMR). The typical symptoms of PMR are muscle pain and stiffness in the shoulder, neck or hip region. Steroids have traditionally been used to treat this condition with great success, although long courses of steroids, up to 2 years in many cases, are often required. This can result in many unwanted side effects including diabetes, high blood pressure, heart disease, cataracts, weak bones with fractures, weak muscles, skin bruising, difficulty sleeping and mood disturbances. In this trial, the steroid dosage will be decreased much more quickly than what is done in routine clinical practice; there is an expectation that steroid therapy will be withdrawn within four months.

Tocilizumab is a medication already on the market that has been FDA approved in the US and Japan for the treatment of rheumatoid arthritis, and in Japan it is also approved for certain types of juvenile idiopathic arthritis (which is like rheumatoid arthritis in children) and Castleman's disease (which is a rare disease that causes enlarged lymph nodes). It is not FDA approved to treat polymyalgia rheumatica at this time. In this study, it will be given as an intravenous infusion once a month for a treatment period of one year. Experiments done on the blood of patients with PMR show one particular cytokine or small molecule that circulates throughout the body, interleukin-6, to be elevated in this disease. Tocilizumab is a medication that is designed to specifically block this cytokine. The co-primary endpoints for this study include efficacy, as well as evaluations of safety and tolerability.

  • Efficacy will be defined by the proportion of patients in Disease Remission (DR) off corticosteroids, without relapse or recurrence, at six months from trial entry
  • Safety and tolerability of Tocilizumab will be evaluated during the fifteen-month study period by the monitoring of adverse events and immunogenicity surveillance

Disease Remission (DR) will be defined as the disappearance of signs and symptoms of polymyalgia rheumatica (aching and stiffness of the shoulder, hip girdle, or both) with normalization of erythrocyte sedimentation rate (ESR<30 mm/hr) and c-reactive protein (CRP ≤1.0 mg/dl), unless elevation of ESR and/or CRP are attributable to causes other than PMR (i.e., infection).


Condition Intervention Phase
Polymyalgia Rheumatica (PMR)
Drug: Tocilizumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIa of Tocilizumab In the Treatment of Polymyalgia Rheumatica

Resource links provided by NLM:


Further study details as provided by Hospital for Special Surgery, New York:

Primary Outcome Measures:
  • Proportion of Patients in Disease Remission at Six Months from Trial Entry [ Time Frame: Six months ] [ Designated as safety issue: No ]

    The co-primary endpoints for this study include efficacy, as well as evaluations of safety and tolerability.

    • Efficacy will be defined by the proportion of patients in Disease Remission (DR) off corticosteroids, without relapse or recurrence, at six months from trial entry
    • Safety and tolerability of Tocilizumab will be evaluated during the fifteen-month study period by the monitoring of adverse events and immunogenicity surveillance

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 15 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients able to achieve Disease Remission (DR) off corticosteroids, without Disease Relapse or Recurrence [ Time Frame: 12 and 15 months from trial entry ] [ Designated as safety issue: No ]
  • Proportion of patients who develop Disease Relapses [ Time Frame: 6, 12 and 15 months from trial entry ] [ Designated as safety issue: No ]
  • The proportion of patients who develop Disease Recurrences [ Time Frame: 6, 12 and 15 months from trial entry ] [ Designated as safety issue: No ]
  • The cumulative dose of prednisone [ Time Frame: 6, 12 and 15 months from trial entry ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: July 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab Drug: Tocilizumab
Tocilizumab, a humanized anti-interleukin-6 receptor antibody, has been FDA approved for the treatment of rheumatoid arthritis (RA). This molecule binds to the IL-6 binding site of human IL-6 receptor, and competitively inhibits IL-6 signaling. Tocilizumab has been shown to be effective as monotherapy in rheumatoid arthritis or in combination with methotrexate. Studies have suggested that Tocilizumab is effective in other inflammatory disorders including systemic onset juvenile inflammatory arthritis, Castleman's disease, Crohn's disease, and Takayasu's arteritis, all diseases marked by elevations of serum IL-6. The recognition of efficacy in Takayasu's arteritis is particularly intriguing given the important phenotypic overlaps between Takayasu's arteritis and giant cell arteritis, which as mentioned above, is a syndrome strongly associated with polymyalgia rheumatica.
Other Name: Actemra

  Eligibility

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

Disease- Specific Inclusion Criteria:

Patients must meet the following inclusion criteria to be eligible for study entry:

Diagnosed with polymyalgia rheumatica and enrolled within one month of diagnosis.

Disease Specific Exclusion Criteria:

Patients will be excluded from the study based on the following criteria:

  • Symptoms or diagnosis of temporal arteritis, including headache, jaw claudication, hyperesthesia of scalp, abnormal palpated temporal artery, visual disturbances, temporal artery biopsy positivity
  • Concurrent rheumatoid arthritis
  • Presence of rheumatoid factor and CCP
  • Other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, polymyositis, dermatomyositis, mixed connective tissue disease
  • Treatment of polymyalgia rheumatica with more than 20mg of daily prednisone or its equivalent at the time of screening
  • Treatment with more than 30mg of daily prednisone or its equivalent since diagnosis. Treatment with 30mg of daily prednisone or its equivalent since diagnosis for more than 2 weeks.
  • More than 4 weeks of corticosteroid therapy prior to enrollment
  • History of bowel perforation within the past five years.
  • Active diverticulitis.
  • Pre-existing or recent onset demyelinating disorders
  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: NCT01396317

Contacts
Contact: Uzunma Udeh 212-774-2123 udehu@hss.edu

Locations
United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 100214898
Sponsors and Collaborators
Hospital for Special Surgery, New York
Genentech
Investigators
Principal Investigator: Robert F Spiera, MD Hospital for Special Surgery, New York
  More Information

No publications provided

Responsible Party: Robert Spiera, MD, Director, Vasculitis & Scleroderma Program, Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT01396317     History of Changes
Other Study ID Numbers: 11081
Study First Received: July 11, 2011
Last Updated: May 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hospital for Special Surgery, New York:
PMR
POLYMYALGIA RHEUMATICA
Tocilizumab
Hospital for Special Surgery
HSS
Robert Spiera

Additional relevant MeSH terms:
Polymyalgia Rheumatica
Giant Cell Arteritis
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Arteritis
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 26, 2014