Efficacy Study of an Anti-Tumor Necrosis Factor (TNF) Alpha Agent in Patients With Hand Osteoarthritis (DORA)

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00597623
First received: January 15, 2008
Last updated: July 25, 2012
Last verified: May 2012
  Purpose

Digital osteoarthritis (DO) which affects the interphalangeal joints and the Metacarpophalangeal (MCP) of the thumb is a common disease, the prevalence of which increases with age (36% of the population aged over 70). Certain forms of DO with clinical manifestations involving inflammatory features are particularly refractory to usual treatments (analgesics, NSAIDs, braces and local injections). The mechanism of osteoarthritis involves two major cytokines: interleukin-1 beta and tumor necrosis factor alpha. TNF alpha is particularly involved in the inflammation process.

The aim of the present study is to study the efficacy of TNF alpha blockers (2 injections of adalimumab compared to placebo injections in patients with severe and refractory hand osteoarthritis.

We hope that such new therapeutic option may induce substantial pain relief.


Condition Intervention Phase
Hand Osteoarthritis
Other: Adalimumab (Humira®)
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Placebo-controlled Trial of the Efficacy of an Anti-TNF Alpha Agent (Adalimumab, Humira®) in Patients With Incapacitating Hand Osteoarthritis Refractory to Usual Treatment

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Level of Pain on visual analogue scale [ Time Frame: 4 weeks following the last injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of tender joints [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Number of swollen joints [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Global assessment of handicap by patient [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Global assessment of handicap by physician [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Duration of morning stiffness [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • DREISER'S algofunctional index [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Cochin hand index [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Weekly pain recording, and recording of analgesic use (acetaminophen) [ Time Frame: at weeks 4, 6, 10, 14, 26 ] [ Designated as safety issue: Yes ]
  • Percentage of non responders according to the number of patients requiring NSAIDS intake during the trial and/or rule out for lack of efficacy [ Time Frame: from week 0 until week 26 ] [ Designated as safety issue: Yes ]

Enrollment: 84
Study Start Date: January 2008
Study Completion Date: December 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
2 injections of Adalimumab (Humira®)
Other: Adalimumab (Humira®)
syringes for injections under cutaneous dose = 40mg vol = 0.8 ml
Placebo Comparator: 2
2 injection of Placebo
Other: Placebo
syringes under cutaneous vol = 8 ml

Detailed Description:

Objective: To demonstrate the efficacy of two subcutaneous injections of anti-TNF alpha (adalimumab) in patients with DO refractory to usual treatments (NSAIDs - analgesics).

Design: Randomized placebo-controlled multicenter (20 sites (amendment 18/12/2008)) trial

Trial duration: 6 months follow-up per patient, total trial duration: 12 months

Number of patients: 84(up)

Dose of administration: Two subcutaneous injections separated by a 2-week interval of either adalimumab or placebo. Therapeutic precautions inherent to the prescription of anti-TNF alpha are based upon those recommended in rheumatoid arthritis. With only two injections of anti-TNF alpha, the risk of complications (infectious in particular) inherent to the anti-TNF alpha appears to be extremely slight.

Patient selection: Patients with digital osteoarthritis (DIP and PIP) according to American College of Rheumatology (ACR) criteria (with a recent X-ray, less than 6 months, of the hands, showing signs of digital osteoarthritis), symptomatic for more than 3 months (at least three finger joints) and scored more than 40 mm on a pain visual analog scale (VAS) despite use of a level 1 analgesic (acetaminophen: 4 g daily) andNSAIDs. Main Exclusion criteria are contraindications to anti-TNF alpha according to international guidelines.

Methods: Patients will be seen at a screening visit, then during treatment administration (W0 and W2) and at follow-up visits: W6, 10, 14 and 26. NSAIDs will be stopped at the time of screening.

Efficacy evaluation: The efficacy endpoint is improvement in pain on a pain VAS at different times of assessment (primary endpoint at W6). A more than 50% improvement, in comparison with baseline, will be considered to be significant. Secondary endpoints are: number of tender joints, number of swollen joints, morning stiffness, global assessment of handicap by patient, global assessment of handicap by physician, the DREISER'S algofunctional index, Cochin hand index, weekly evolution of pain ( patient record), and recording of analgesic use (acetaminophen or NSAIDs).

Statistical data: Statistical analysis will be performed on the inter-group difference in the intention-to-treat population. khi-2 will be used only for criteria number 1.

Anticipated result: Significant superiority of adalimumab over placebo which would provide a therapeutic solution in difficult-to-treat patients with hand OA.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 40-80
  • Men or women
  • Digital osteoarthritis (DIP and PIP) according to ACR criteria (with recent X-ray, dating from less than 6 months, of the hands showing radiological signs of digital osteoarthritis)
  • Symptomatic digital osteoarthritis for more than 3 months (at least every other day) despite taking analgesics and NSAIDs (except when there are contraindications to the latter therapeutic group)
  • Osteoarthritis affecting more than three finger joints
  • Pain more than 40 mm as evaluated by pain VAS (0-100 mm)
  • No contraindication to anti-TNF alpha treatments
  • No digital osteoarthritis surgery scheduled within the next 2 months
  • Written informed consent

Exclusion Criteria:

  • Pregnant women or women of reproductive potential without effective contraception
  • Known hypersensitivity
  • Patients having already been treated with an anti-TNF alpha
  • Finger osteoarthritis secondary to inflammatory rheumatism
  • Psoriasis
  • Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain (cervicobrachial neuralgia, incapacitating carpal tunnel syndrome, joint disorders of the elbow or shoulder)
  • Inflammatory rheumatism
  • Contraindications to anti-TNF alpha agents: patients with suspected reactivation of tuberculosis (phlyctenular IDR, past history of tuberculosis, chest X-ray deemed suspect) or known leukopenia (< 3500 leukocytes), known hepatic cytolysis (transaminases more than twice normal), a history of serious allergy, concomitant infection, past history of serious systemic infection (septicemia), a history of known cancer within the past 5 years, history of multiple sclerosis
  • Skin disease incompatible with subcutaneous injection
  • Anticoagulant (oral) or treatment with heparin at a curative dose
  • Surgery scheduled within the coming 2 months
  • Finger surgery scheduled within the coming 6 months
  • Local injection of a corticosteroid in a symptomatic finger joint during the previous month
  • Local injection of hyaluronic acid in a symptomatic finger joint during the prior 3 months
  • Treatment with a slow-acting anti-osteoarthritis agent initiated and colchicine (amendment 26/06/2008) within the previous 3 months
  • Oral corticosteroids
  • Psychiatric illness
  • Non-controlled diabetes "mellitus"
  • Known viral hepatitis B or C, HIV 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: NCT00597623

Locations
France
CHU Henri Mondor
Créteil, France, 94000
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Abbott
Investigators
Principal Investigator: Xavier Chevalier, PU-PH AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00597623     History of Changes
Other Study ID Numbers: P 051007
Study First Received: January 15, 2008
Last Updated: July 25, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Osteoarthritis
Hand
Tumor Necrosis Factor-alpha inhibitors
Biological Therapy

Additional relevant MeSH terms:
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014