Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches (ABC)
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|ClinicalTrials.gov Identifier: NCT02270957|
Recruitment Status : Active, not recruiting
First Posted : October 22, 2014
Results First Posted : November 25, 2020
Last Update Posted : November 17, 2021
|First Submitted Date ICMJE||October 13, 2014|
|First Posted Date ICMJE||October 22, 2014|
|Results First Submitted Date ICMJE||October 6, 2020|
|Results First Posted Date ICMJE||November 25, 2020|
|Last Update Posted Date||November 17, 2021|
|Study Start Date ICMJE||January 2014|
|Actual Primary Completion Date||December 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA) [ Time Frame: 6 months ]
The British Isles Lupus Assessment Group Index is a scoring system for progress of disease activity over the prior month with a scoring system that rates each organ system as "A" or severe, "B" or moderate, "C" or mild vs no activity in the past month. To meet the BICLA endpoint requires all baseline severe features (BILAG A) improving to moderate (BILAG B), mild or resolved, and all baseline BILAG B features improving to mild or resolved without increase in any other feature on either the BILAG or a different measure called the SLEDAI (SLE Disease Activity Index). Furthermore there must be no increase in Physician's Global Assessment or any rescue medications after the month 2 visit. Only those meeting all of these criteria meet the primary endpoint.
|Original Primary Outcome Measures ICMJE
||BILAG-based Combined Lupus Assessment (BICLA) [ Time Frame: 6 months ]
All baseline severe features (BILAG A) improving to moderate (BILAG B) or better and all baseline BILAG B features improving to mild or resolved (C or D) without increase in any other feature on BILAG or SLEDAI (SLE Disease Activity Index), increase in Physician's Global Assessment or rescue medications after the month 2 visit
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures
|Brief Title ICMJE||Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches|
|Official Title ICMJE||Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches (The ABC Study)|
|Brief Summary||This is a randomized, double blind, placebo controlled trial of abatacept for the treatment of lupus arthritis and other manifestations of lupus. Patients with lupus and at least 3 tender and 3 swollen joints and </= 20 mg prednisone have other background immune suppressants withdrawn at entry. They can elect to receive up to a total of 320 mg depomedrol (in two or more injections) between the screening visit and the visit 2 months after dosing begins. Abatacept (125 mg) or placebo is administered in weekly subcutaneous doses. After 3 months of treatment patients who are not responding may elect to receive open label abatacept with or without additional standard of care therapies. Such patients are considered non responders. The primary endpoint is the British Isles Lupus Assessment Group Index (BILAG)-linked Combined Lupus Assessment (BICLA) which will require a clinically significant improvement in arthritis and other active features of lupus|
Research Hypothesis: Abatacept is effective in lupus arthritis and this will be discernible in a small trial with robust endpoints which incorporates withdrawal of background immune suppressants
Study Schematic: Abatacept 125 mg or placebo will be given in a 1:1 randomization subcutaneously each week for six months. All patients may elect to continue six more months on open label Abatacept. Background Immune Suppressants will be withdrawn at any time between screening and the first dosing visit. At or after screening, patients may elect 40-160 mg depomedrol shots prn not to exceed 320 mg total up to and including the Month 2 Visit (two months after the first dosing visit) After that, additional steroids or immune suppressants, if necessary, will be allowed but the patient will be considered a non-responder in the primary endpoint at six months on that basis. At of after the 3 month visit patients with significant clinical flare may also elect to receive open label Abatacept but will be considered non-responders in the primary endpoint at six months.
Primary Objective: To compare response rates between Abatacept-Treated and Placebo-Treated Patients with active lupus arthritis in a trial designed with background immune suppressant withdrawal, limited steroid rescue, and a robust, discriminatory endpoint. The trial design and primary endpoint of response by BICLA (defined below) have been pre-tested by us for safety and ability to ensure placebo group non-response, underscoring our powering of the study. This will support a rational decision about further development of abatacept for SLE at minimal cost.
Secondary clinical outcome measures used as endpoints will include: SRI 4/5, changes in joint counts, SLEDAI, BILAG, CLASI, PGA, and LFA REAL measures.
The definitions of the clinical outcome measures are as follows: BICLA: BILAG-based Combined Lupus Assessment, This is defined as British Isles Lupus Assessment Group (BILAG) index scores that were severe at entry (BILAG A scores) improving to a moderate (BILAG B) level (or better) and all features that were moderate at entry improving to a mild level (BILAG C scores) or resolved (BILAG D scores) without increase in any other BILAG feature or SLEDAI scoring (see SLEDAI definition below), as well as no more than 10% worsening in a Physician's Global Assessment or any additional treatments after the protocolized baseline rescue (e.g. no new SLE treatments after the two month visit). SLEDAI stands for the Systemic Lupus Erythematosis Disease Activity Index. SRI 4/5 is defined as SLEDAI improvement by at least 4 points (or 5 points respectively), no increase in BILAG-measured disease activity and no more than 10% worsening in a Physician's Global Assessment (PGA). CLASI stands for the Cutaneous Lupus Erythematosus Disease Area and Severity Index. PGA stands for Physician's Global Assessment. LFA REAL stands for the Lupus Foundation of America Rapid Evaluation of the Activity of Lupus. This instrument is in a pilot phase but will be tested in the ABC study.
PK and immunogenicity studies will also be performed to help in interpretation of outcomes. Novel biologic discovery will be integrated into the clinical trial to support both pre-specified and exploratory biomarker discovery. Data will be generated that might be used to help select more appropriate patient subsets for future trials and, along with PK data, help to guide optimal dosing strategies. Optimizing patient selection and dosing are important goals for further increasing demonstrable effect size in trials by increasing the response rates in the treatment group.
This study will be performed as a double blind, randomized, placebo-controlled clinical trial with 1:1 randomization of patients to abatacept 125 mg weekly subcutaneous dose or placebo, with the withdrawal of background immune suppressants. Limited steroid rescue is allowed between the screening visit and the Month 2 visit per protocol. Additional standard of care rescue medications may be used after that as needed but will define non-response at the primary endpoint date of six months. Flaring patients may elect to receive open label abatacept at Month 3 but will also be defined as non-responders in the primary endpoint. All patients may elect to receive open label abatacept for an additional six months after the primary endpoint date, with two follow up visits (2 and 4 months post medication withdrawal) to assess withdrawal effects and to complete the safety assessments.
Accrual Goal: This study will continue to recruit until we achieve the goal of 60 patients who complete study visits through the 6 month endpoint.
Correlative Studies: Extensive exploratory protocol-specific and ancillary immune pharmacodynamic studies, focusing first on changes in IFN alpha, BLyS and other B Cell pathways. A major focus will also be on T Cell pathways with a focus on T suppressor/TH17 dichotomy after treatment with abatacept. A responder analysis will be performed in order to generate hypotheses useful for selecting appropriate patients for this treatment and optimizing dosing strategies.
Adverse Events, Serious Adverse Events and Adverse Events of special interest (infusion reactions and infections) will be collected and described. Stopping Rules: Patients may be withdrawn by the investigator for non-compliance or safety. All patients terminating before six months will be considered non responders in the primary analysis. Use of off protocol immune suppressants will not necessarily dictate withdrawal but will determine non-responder status. A DSMB board of at least two physicians (four are currently participating) will review data and may stop the study if needed.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Condition ICMJE||Systemic Lupus Erythematosus|
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||December 2021|
|Actual Primary Completion Date||December 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT02270957|
|Other Study ID Numbers ICMJE||OMRF 13-38|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||
|Responsible Party||Oklahoma Medical Research Foundation|
|Study Sponsor ICMJE||Oklahoma Medical Research Foundation|
|Collaborators ICMJE||Bristol-Myers Squibb|
|PRS Account||Oklahoma Medical Research Foundation|
|Verification Date||November 2021|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP