Study of Tocilizumab to Treat Polymyalgia Rheumatica

Phase IIa of Tocilizumab In the Treatment of Polymyalgia Rheumatica

This is a 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).

Study Overview

• Status: Completed
• Conditions: Polymyalgia Rheumatica (PMR)
• Intervention / Treatment: Drug: Tocilizumab

Detailed Description

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much more quickly than what is done in routine clinical practice; there is an expectation that steroid therapy will be withdrawn within six months.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).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 100214898
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab; This is a single-arm study. All subjects will receive the active study treatment for 12 months, and will then be evaluated for 3 months of long-term follow-up.	Drug: Tocilizumab; Tocilizumab is a humanized anti-interleukin-6 receptor antibody that 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.; Other Names: Actemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients in Disease Remission at Six Months From Trial Entry	The co-primary endpoints for this study include efficacy: • 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 Relapse was defined as the reappearance of signs and symptoms of PMR, accompanied by an increasing erythrocyte sedimentation rate and/or C-reactive protein level attributable to disease activity. Recurrence was similarly defined as the return of PMR symptoms in conjunction with elevations in levels of inflammation markers, occurring 1 month after discontinuation of glucocorticoid therapy.	Six months
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	The co-primary endpoints for this study include evaluations of safety and tolerability: • Safety and tolerability of Tocilizumab will be evaluated during the fifteen-month study period by the monitoring of adverse events and immunogenicity surveillance	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Able to Achieve Disease Remission (DR) Off Corticosteroids, Without Disease Relapse or Recurrence		12 and 15 months from trial entry
Proportion of Patients Who Develop Disease Relapses	Relapse was defined as the reappearance of signs and symptoms of PMR, accompanied by an increasing erythrocyte sedimentation rate and/or C-reactive\ protein level attributable to disease activity. Recurrence was similarly defined as the return of PMR symptoms in conjunction with elevations in levels of inflammation markers, occurring 1 month after discontinuation of GC therapy.	6, 12 and 15 months from trial entry
The Cumulative Dose of Prednisone		6, 12 and 15 months from trial entry
Total Number of Relapses/Recurrences		12 months

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Robert F Spiera, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 15, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Actual): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 15, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Tocilizumab; PMR; POLYMYALGIA RHEUMATICA; Hospital for Special Surgery; HSS; Robert Spiera
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Arteritis; Polymyalgia Rheumatica; Giant Cell Arteritis
• Other Study ID Numbers: 11081