Impact of Subcutaneous Abatacept in Rheumatoid Arthritis Assessing Inhibition of Structural Damage

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Orrin M Troum, M.D. and Medical Associates
ClinicalTrials.gov Identifier:
NCT01333878
First received: April 7, 2011
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

The hypothesis of this study is that subcutaneous Abatacept is effective in reducing synovial inflammation, osteitis, and erosions in Rheumatoid Arthritis as assessed by low field extremity MRI and X-ray.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Subcutaneous Abatacept
Phase 2
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Pilot Trial to Assess the Impact of Subcutaneous Abatacept in Rheumatoid Arthritis Assessing Inhibition of Structural Damage Determined by Low Field Extremity MRI (eMRI) and X-ray

Resource links provided by NLM:


Further study details as provided by Orrin M Troum, M.D. and Medical Associates:

Primary Outcome Measures:
  • Inhibition & progression of structural damage [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assess inhibition & progression of structural damage in MTX inadequate responders with moderate to severe active RA on SC Abatacept plus MTX, utilizing eMRI and X-ray at baseline, eMRI at Week 12, and eMRI and X-ray final assessment at week 24.


Secondary Outcome Measures:
  • Improvement in ESR-based DAS28 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assess improvement in ESR-based DAS28, physician global assessment, and improvement in HAQ score


Enrollment: 12
Study Start Date: March 2011
Study Completion Date: January 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-Label Subcutaneous Abatacept
Open-Label Subcutaneous Abatacept
Biological: Subcutaneous Abatacept
Subcutaneous Abatacept 125 mg once weekly for 6 months

Detailed Description:

This is an open-label study of the efficacy of subcutaneous (SC) Abatacept to inhibit progression of structural joint damage in patients with active rheumatoid arthritis (RA) receiving MTX and have inadequate disease control (defined as an ESR based DAS28 ≥ 3.2 AND ≥ 6 swollen and ≥ 6 tender joints). The study consists of a screening period (Days -21 to -7), a baseline visit (Days -20 to -1), and a treatment Period (open label Abatacept 125 mg SC for 24 weeks). All the visits may occur at the indicated week +/- 2 days. The last efficacy assessments are to be conducted at Week 24 and subjects are to be contacted by telephone for a safety follow-up 2 months after the final study agent has been administered.

The maximum length of the study is 35 weeks, which includes the 2-week screening period, 1-week baseline period, 24-week open label treatment, and 8-week follow-up period. Eligible subjects are to continue their current MTX treatment regimen, a stable dose of at least 15mg/week, during the entire length of the study (24 weeks). At Day 0, patients who meet inclusion criteria, will be dosed from Day 0 to Week 24 with Abatacept 125 mg SC injection.

Subjects are to self-administer SC study agent at Weeks 5, 6, 7, 9, 10, 11, 13, 14, 15, 17, 18, 19, 21, 22, and 23 and are not required to return to the study site at these weeks. All other visits, SC study agent is to be administered while the subject is at the study site.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects currently experiencing active moderate to severe RA according to the revised 1987 ACR criteria for the diagnosis of RA at screening. The ESR-based DAS 28 must be equal or greater than 3.2
  2. MTX inadequate responders with moderate to severe RA. Subjects currently receiving MTX for at least 12 weeks and who have received MTX at a stable dose (≥15mg/week) for at least 6 weeks prior to treatment (Day 0). They must be biologic drug naive
  3. All subjects must receive at least 5 mg oral folic acid weekly.
  4. At screening active RA as defined by ≥ 6 swollen joints and ≥ 6 tender joints with erythrocyte sedimentation rate (ESR) ≥ 28 mm/h.
  5. Subjects must be seropositive with documented rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti CCP) positivity. If a documented history of RF or anti CCP positivity is not available, RF and anti CCP titers will be obtained at screening
  6. MRI evidence of at least one joint with osteitis or erosion attributable to RA as determined by an MRI musculoskeletal radiologist. Any joint of the dominant hand or wrist can be considered with the exception of distal interphalangeal joints of the hands.
  7. If subjects are receiving an oral corticosteroid, the dose must be ≤10 mg/day prednisone (or equivalent) and stable for at least 28 days prior to treatment (Day 0).
  8. Subjects able and willing to give written informed consent and comply with the requirements of the study protocol. Informed consent must be obtained prior to any study-related procedures.

    A copy of the signed informed consent form must be given to the subject

  9. Subjects must be willing to self-inject or allow a caregiver to administer the subcutaneous injection

Exclusion Criteria:

  1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
  2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome). Prior history of or current inflammatory joint disease other than RA (gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis and psoriatic arthritis)
  3. Functional class IV as defined by the ACR Classification of Functional Status in RA
  4. Current treatment with any traditional DMARDs other than MTX within 4 weeks before the screening visit
  5. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
  6. Exposure to any Biologic Response Modifying Agent
  7. Intra Articular or parenteral corticosteroids within 6 weeks prior to screening
  8. Immunization with live vaccine within 3 months prior to enrollment and a need for a live vaccine during the study
  9. Subjects who have a metal device where the use of MRI is contraindicated (e.g.,any type of electronic, mechanical, or magnetic implant; cardiac pacemaker, aneurysm clip; implanted cardioverter defibrillator; or a cochlear implant). Subjects who have a potential ferromagnetic foreign body (metal shavings, metal slivers, other metal objects) for which they have sought medical attention
  10. Exclusionary laboratory: Serum creatinine >2 mg/dL, ALT or AST > 2.0 x ULN, total bilirubin > 2.0 x ULN, platelet count <100 x 109 /L, hemoglobin < 8.5 g/dL, WBC count < 1,000/mm3 , absolute neutrophil count < 1,000/ mm3, absolute lymphocyte count < 500/mm3, positive HBsAg or HCV antibody, or positive HIV test.
  11. Pregnant women or nursing mothers
  12. Females of child bearing potential who are not using reliable means of contraception
  13. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine or GI disease
  14. Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel syndrome, where flares are commonly treated with corticosteroids
  15. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections such as atypical mycobacterial disease, hepatitis B and C, HIV, herpes zoster, or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
  16. A history of active TB within the last 3 years even if it was treated. A history of active TB greater than 3 years ago unless there is documentation that the prior anti-TB treatment was appropriate in duration and type. A positive PPD skin test (≥5 mm) or positive QuantiFERON-TB Gold serum test without appropriate prophylaxis (at least 1 month of the planned local guidelines treatment regimen)
  17. Any malignancy except for skin cancer (basal cell or squamous cell) diagnosed within the previous 5 years
  18. History of alcohol, drug, or chemical abuse
  19. Neuropathies or other painful conditions that might interfere with pain evaluation
  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: NCT01333878

Locations
United States, California
Orrin M. Troum, MD and Medical Associates
Santa Monica, California, United States, 90404
Sponsors and Collaborators
Orrin M Troum, M.D. and Medical Associates
Bristol-Myers Squibb
Investigators
Principal Investigator: Orrin M Troum, MD Orrin M. Troum, MD & Medical Associates
  More Information

No publications provided

Responsible Party: Orrin M Troum, M.D. and Medical Associates
ClinicalTrials.gov Identifier: NCT01333878     History of Changes
Other Study ID Numbers: BMS IM101-281
Study First Received: April 7, 2011
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014