Rheumatoid Arthritis Memory B Cells and Abatacept (RAMBA) (RAMBA)
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|ClinicalTrials.gov Identifier: NCT03652961|
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : January 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: Abatacept||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Rheumatoid Arthritis Memory B Cells and Abatacept (RAMBA)|
|Actual Study Start Date :||December 21, 2018|
|Estimated Primary Completion Date :||September 1, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Open Label abatacept for Intravenous Infusion Abatacept intravenous will be administered as a 30-minute intravenous infusion utilizing the weight range-based dosing. Following the initial intravenous administration, an intravenous infusion will be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter for a total of 7 doses.
- Clinical response of abatacept and conventional synthetic disease-modifying anti-rheumatic drugs to induce low disease activity- PBMC collection [ Time Frame: 24 weeks ]
- Direct quantitation of the frequency of circulating Anti-citrullinated protein antibodies (ACPA)-bearing memory B cells as a percentage of total B cells and memory B cells at baseline and at followup as measured by flow cytometry. These will be correlated with clinical response.
- Flow cytometric determinations of effects on B-cell subsets, to determine whether abatacept normalizes disease-associated increases in activated memory B cells, and the plasmablast expansions that are associated with active RA disease.
- Serum will be collected for cytokine/chemokine profiling, which will be highly informative due to the challenge/dechallenge design.
Site will count absolute numbers of PBMC in samples obtained from defined volume of blood and calculate percentages of B cell subsets, CD4 vs CD19 ratios. And percentages of Memory vs naïve B cells amongst CD45 positive cells.
- Clinical response of abatacept and conventional synthetic disease-modifying anti-rheumatic drugs to induce low disease activity- [ Time Frame: 24 weeks ]To evaluate the effects of abatacept on circulating Immunoglobulin M (IgM), Immunoglobulin G (IgG), and IgG-ACPA antibody levels, in assays using a panel of matched citrulline- and arginine-containing peptides/self-proteins. Antibody responses will be in standardized assays with relative units per ml, assessed in an ELISA or bead based assay, at 1:100, 1:1000 and 1:10,000 dilutions.
- Quantification of relationships between co-primary endpoints over time and then confirm this relationship by dechallenge of Abatacept after induction of low disease activity at 24 weeks - RAPID-3 questionnaire [ Time Frame: 24 weeks ]
Abatacept therapy that induces clinical benefits, are paralleled by reductions (i.e., normalization) in the in vivo representation of disease-associated anti-citrullinated protein antigen (ACPA) memory B cells after 6 months of treatment. Response will be measured by RAPID-3 questionnaire.
The RAPID3 includes a subset of core variables found in the Multi-dimensional Health Assessment Questionnaire HAQ (MD-HAQ, scoring of physical function from 1-10 , a patient global assessment (PGA) for pain from 1-10, and a PGA for global health from 1-10. RAPID3 scores are quickly tallied by adding subsets of the MD-HAQ.
-Scoring 1-10 where 10 is maximal activity
A patient who scores between 0-1.0 is defined as near remission (NR); 1.3-2.0 as low severity (LS); 2.3-4.0 as moderate severity (MS); and 4.3-10.0 as high severity (HS).
- Quantification of relationships between co-primary endpoints over time and then confirm this relationship by dechallenge of Abatacept after induction of low disease activity at 24 weeks - Clinical Disease Activity Index (CDAI). [ Time Frame: 24 weeks ]
The CDAI is a clinical composite score for following patients with rheumatoid arthritis.
CDAI = SJC(28) + TJC(28) + PGA + EGA SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) PGA: Patient Global disease Activity (patient's score of overall RA disease activity on a scale 1-10 where 10 is maximal activity) EGA: Evaluator's Global disease Activity (evaluator's score of overall RA disease activity on a scale 1-10 where 10 is maximal activity) INTERPRETATION Remission CDAI ≤ 2.8 Low Disease Activity CDAI > 2.8 and ≤ 10 Moderate Disease Activity CDAI > 10 and ≤ 22 High Disease Activity CDAI > 22 A CDAI reduction of 6.5 represents moderate improvement.
- Quantification of relationships between co-primary endpoints over time and then confirm this relationship by dechallenge of Abatacept after induction of low disease activity at 24 weeks - tender and swollen joint count [ Time Frame: 24 Weeks ]SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) Joint Assessor will conduct a standard 28 tender and swollen joint count of patient at each visit throughout the trial. The swollen joint count is the amount of inflamed synovial tissue, and the tender joint count scores the level of pain. This score will be used in the Clinical Disease Activity Index (CDAI) calculation.
- Quantification of relationships between co-primary endpoints over time and then confirm this relationship by dechallenge of Abatacept after induction of low disease activity at 24 weeks - Disease Activity Score using C-reactive protein test. [ Time Frame: 24 weeks ]
DAS28 is calculated according to the formula that is composed of the number of tender joints and swollen joints, patient's global assessment of disease activity on a visual analogue scale (VAS) from 1-10 (10 is maximal activity) , and C‐reactive protein (CRP) lab results.
CRP is measured in milligrams of CRP per liter of blood (mg/L). Normal CRP levels are below 3.0 mg/L.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652961
|Contact: Ashley E Switzer||6036508587||Ashley.email@example.com|
|Contact: Jill Brooker, RN||6036504717||Jill.B.Brooker@hitchcock.org|
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Ashley Switzer 603-650-4717 Ashley.firstname.lastname@example.org|
|Contact: Jill Brooker 6036504717 Jill.email@example.com|
|Principal Investigator:||William Rigby, MD||Dartmouth-Hitchcock Medical Center|