Clinical trial NCT02429934: Abatacept for SLE Arthritis (IM101-330)
Official title: Efficacy of Abatacept in Inflammatory Polyarthritis of Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus Arthritis
Keywords: Systemic Lupus Erythematosus (SLE)
Abatacept (Orencia)
Arthritis
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-04-29
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research trial is for patients who have been diagnosed with systemic lupus erythematosus (SLE) with swollen, tender joints (which is called inflammatory polyarthritis) because of the SLE.

The purpose of this clinical research study is to evaluate the safety and effectiveness of treatment with abatacept (Abatacept) 125mg injected subcutaneously (under the skin) weekly for 16 weeks versus placebo injections(a substance with no active ingredients and therefore may have no treatment benefit) in subjects with SLE and inflammatory polyarthritis. The effectiveness will be assessed primarily by the number of swollen, tender joints (called a joint count) at each of study visits.

Study Medication Abatacept is approved in the U.S. for treating rheumatoid arthritis by prescription and has not been approved by the U.S. Food and Drug Administration for treating SLE yet.

In this study, subjects will receive treatment with either abatacept or placebo once a week for 16 weeks (a total of 16 injections).


Eligibility criteria: Inclusion Criteria:

1. Meet at least 4 of the 11 American College of Rheumatology (ACR) 1997 criteria for classification of SLE (see Appendix 1).OR meet the recent classification recommended by SLICC (Appendix 2) 6
2. ≥3 swollen and tender joints on 2 examinations at least 2 weeks apart and no more than 8 weeks apart.
3. SLEDAI2K score ≥4 indicating active disease.
4. Documented positive ANA (≥1:80) and/or anti-dsDNA during course of SLE.
5. Men and women, at least 18 years of age. Women of childbearing potential must use adequate method(s) of contraception to avoid pregnancy throughout the study and for up to 2 months after last study drug dose. They must have a negative serum or urine pregnancy test prior to the start of study medication.
6. Background therapies allowed: antimalarials (dose constant for ≥ one month before study entry and during 16 weeks of trial), methotrexate (same criteria as for antimalarials), azathioprine (same criteria), mycophenolate (same criteria), leflunomide (same criteria).

During the screening period and for up to 6 weeks after randomization, a daily prednisone (or equivalent) regimen of up to 20 mg daily may be initiated to treat the moderate to severe disease activity present at screening. The initial steroid regimen is not required if investigators or patients believe that the risks would outweigh the potential benefits. Patients who do not take any glucocorticoids during the study will be included in the treatment groups and analysis.

\*Steroids should be tapered to a target dose of no more than 10 mg/day of prednisone (or equivalent) by the end of Week 8 (Day 56). The steroid regimen should be tapered as quickly as safely possible. Prednisone dose requirements higher than 10 mg daily at the 8 week visit will cause the patient to be ruled a non-responder for the abatacept treatment arm.

Exclusion Criteria:

1. Subjects with active infection requiring oral or IV antibiotics within one month of first dose of study medication.
2. Subjects with BILAG A in any system outside the musculoskeletal system.
3. Subjects with positive quantiferon Gold test in the absence of treatment for tuberculosis.
4. Subjects with positive tests for active infection with hepatitis B or C during the past 6 months. Any confirmed positive test for HIV at any time prior to entry into this study.
5. Subjects with active glomerulonephritis (\>3 g protein/24h and/or active urine sediment).
6. Subjects with active CNS disease.
7. Subjects with any other serious disease that would require immunosuppressive or parenteral anti-microbial therapy outside the study protocol.
8. Inability to self-administer subcutaneous injections, to comply with instructions, or to keep appointments for study visits.
9. Treatment with rituximab within the past 6 months (B cells must be detectable in peripheral blood at onset of treatment with study biologic), belimumab within the past 5 months, cyclophosphamide within the past 3 months.
10. Treatment with any other immunomodulatory biologic or cyclophosphamide during treatment with abatacept is not allowed.
11. Patients requiring \>20 mg of prednisone daily.
12. Women who are pregnant or breast feeding.
13. Women of child bearing potential unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 2 months after last study drug.
14. Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection).
15. Any laboratory test results that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.

Primary outcomes:
measure: Number of Participants With at Least a 20% Improvement From Baseline in Tender and Swollen 28 Joint Count
timeFrame: Baseline, 8 Weeks, 16 Weeks
Secondary outcomes:
measure: Change in SLEDAI 2K
timeFrame: Baseline, 16 weeks
measure: Change in the PGA Score
timeFrame: Baseline, 16 weeks
measure: Clinical Disease Activity Index (CDAI) Index Score
timeFrame: 16 weeks
measure: Synovitis, Tenosynovitis and Erosions Scores (GSUS and PDUS)
timeFrame: Baseline, 16 weeks
measure: Number of AEs and SAEs
timeFrame: 16 weeks
measure: Number of Tender and Swollen Joints
timeFrame: baseline, 4, 8, 12 and 16 weeks
measure: Change in the Total Sum of Tender and Swollen Joints
timeFrame: Baseline, 16 weeks
measure: Number of Patients Who Tapered Prednisone to <10mg/Day
timeFrame: 16 weeks
measure: Mean Prednisone Dose (mg/Day)
timeFrame: Baseline, 8 and 16 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine, Division of Rheumatology
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Bevra Hahn, M.D.
role: PRINCIPAL_INVESTIGATOR
References: