Infliximab Therapy in Patients With Refractory Polymyalgia Rheumatica

NCT01423591 | Unknown Phase 3 DMC

• 1 other identifier: P04578
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatic Polymyalgia(PMR) is a relatively common chronic inflammatory disorder of unknown origin which predominantly develops in elderly subjects and presents with severe pain and stiffness in the neck, shoulder and pelvic girdles, along with increased acute phase reactants. Systemic manifestations such as fever, anorexia and weight loss are characteristic signatures of PMR. Corticosteroids (CS) constitute the standard treatment of PMR. Although in most patients the symptoms of the disease disappear after one or two years of treatment, a proportion of patients remain CS-dependent with the subsequent CS toxicity. Open label studies have suggested that tumour necrosis factor (TNF) antagonists lead to sustained improvement and CS sparing effect in patients with refractory PMR. The investigators conducted a randomised, double-blind, placebo controlled trial with infliximab in CS-dependent patients with PMR. Patients with CS-dependent PMR (defined as requiring ≥ 5 mg/day after at least 2 years of treatment to maintain remission or ≥ 7.5 mg/day after at least 6 months) were randomly assigned to receive Infliximab (5 mg/kg i.v) at 0, 2, 6, 14 and 22 weeks (n = 12) or placebo (n = 11) together with CS that were reduced according to a predefined schedule. The primary outcome was the proportion of responder patients -defined as individuals with both complete clinical and analytical remission without receiving CS for at least three months- at 24 weeks. Secondary outcomes were cumulative CS doses and adverse events proportion.

Conditions

Polymyalgia Rheumatica

Keywords

Infliximab; polymyalgia rheumatica; refractory; double blind; placebo controlled; trial

Outcome Measures

Primary Outcomes (1)

• Proportion of responders(complete remission without corticosteroids)

  at 24 weeks

Secondary Outcomes (7)

• Proportion of responders

  at 48 weeks

• Time to response

  48 weeks

• Number of relapses / recurrences

  48 weeks

• Response duration

  48 weeks

• Cumulative dose and side effects of steroids

  at 24 and 48 weeks

Study Arms (2)

infliximab

EXPERIMENTAL

Drug: infliximab

inactive powder

PLACEBO COMPARATOR

Drug: inactive powder

Interventions

infliximab DRUG

Infliximab 5 mg/kg. i.v. at week 0, 2, 6, 14 y 22.

Also known as: Remicade, anti-TNF monoclonal Therapy

infliximab

inactive powder DRUG

Inactive powder. i.v. at week 0, 2, 6, 14 y 22.

Also known as: placebo

inactive powder

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• PMR patients that after 2 years of corticosteroid treatment are not able to reduce the dose of prednisone below 5 mg/day or equivalent.
• PMR patients that after 6 months of corticosteroid treatment are not able to reduce the dose of prednisone below 7,5 mg/day or equivalent.
• PMR patients should fulfill the criteria proposed by Chuang et al (8):
• Age ≥ of 50 years.
• Development of bilateral moderately/severe aching and stiffness persisting for 1 month or more, involving two of the following areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs.
• ESR ≥ 40 mm/h.
• Complete clinical response to low-dose of steroids (prednisone or equivalent ≤ 20mg/day)

You may not qualify if:

• Patients with biopsy-proven GCA or those with cranial symptoms or signs suggestive of GCA but without biopsy-proven arteritis.
• Patients with clinical features suggestive of RA or other connective tissue disorders.
• Chronic infections such as HIV, hepatitis B or C, active mycobacterial or fungal infections, etc.
• Neoplasm or a history of malignancy in the preceding 5 years.
• Patients with multiple sclerosis or other demilinizating disorders.
• Patients with cytopenias: leukopenia (leukocytes ≤ 3.5x109/L.), thrombocytopenia (platelets ≤ 100x109/L.) and/or anemia (≤ 10 g./dl.)
• Patients with cardiac failure (functional class III / IV).
• Any other condition that contraindicates Infliximab therapy

Sponsors & Collaborators

• Hospital Universitario Marqués de Valdecilla: lead
• Schering-Plough: collaborator

Study Sites (1)

Reumatology division, Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Víctor M Martínez-Taboada,, Md, PhD

  Servicio de Reumatología, Hospital Universitario Marques de Valdecilla

  STUDY DIRECTOR

• Vicente Rodriguez-Valverde, MD, PhD

  Servicio de Reumatología, Hospital Universitario Marques de Valdecilla

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Rheumatology, MD, PhD

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: August 26, 2011
• Study Start: June 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: December 1, 2011
• Last Updated: August 26, 2011

Record last verified: 2011-08

Locations

ES (1)