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The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients (SYBRA)

Primary Purpose

Rheumatoid Arthritis

Status
Withdrawn
Phase
Phase 3
Locations
United Arab Emirates
Study Type
Interventional
Intervention
Anti-TNF
JAK inhibitor
Sponsored by
Abu Dhabi Stem Cells Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Synovial biopsy, Biologic therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject should be capable of consent
  • Age 18 and older
  • Classified as rheumatoid arthritis as per EULAR/ACR criteria 2010
  • Failed one DMARD (Methotrexate, leflunomide, Sulfalsalazine, hydroxychloroquine)
  • Can be on steroid dose <7.5mg
  • Quantiferon negative
  • Hepatitis B, C negative
  • No recent history (<5y) of malignancy

Exclusion Criteria:

  • Overlap syndrome
  • Previously treated with a biological medication
  • Heart failure NYHA III/IV
  • Active tuberculosis
  • Active infections
  • Previous history of DVT, PE, or Stroke
  • Other significant comorbidities that will prevent them from taking any biologic medication as per EULAR guidelines on treating rheumatoid arthritis 2020.
  • Pregnancy

Sites / Locations

  • Abu Dhabi Stem Cells Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group A (Anti-TNF)

Group B (JAK inhibitor)

Group C (Anti-TNF or JAK inhibitor)

Arm Description

Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the diffuse myeloid phenotype will be assigned to receive anti-TNF medication at the discretion of the treating physician.

Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the lymphoid- myeloid phenotype will be assigned to receive JAK inhibitor medication at the discretion of the treating physician.

Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the pauci-cellular phenotype will be randomized to either anti-TNF or JAK inhibitor medication 1:1.

Outcomes

Primary Outcome Measures

Change in DAS28 score
Change in DAS28 score indicating remission compared to baseline in at least 50% of patients, where DS28<2.6 indicated remission. * DAS score: disease activity score, where <2.6 indicates remission, 2.6-3.2 low disease activity. 3.2-5.1 moderate disease activity; >5.1 high disease activity; higher values suggest worse outcomes.

Secondary Outcome Measures

Change in HAQ score
Significant decrease in HAQ score compared to baseline. * HAQ (Health assessment questionnaire). Scores vary from 0-to 3. Higher scores are associated with worse outcomes.
Change in power Doppler activity
Change in power Doppler activity compared to a baseline where no power Doppler activity indicates remission. Measurement in Doppler activity on ultrasound using a grading system developed by EULAR. * Global EULAR-OMERACT Synovitis Score: scores range from 0-3 for each scanned joint. Higher scores correlate with worse outcomes.
Change in cellular phenotype
Change in cellular phenotype compared to baseline. Estimation of change in the number of inflammatory cells as per the grading criteria.

Full Information

First Posted
May 12, 2022
Last Updated
March 13, 2023
Sponsor
Abu Dhabi Stem Cells Center
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1. Study Identification

Unique Protocol Identification Number
NCT05379322
Brief Title
The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients
Acronym
SYBRA
Official Title
The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Decision of the local healthcare authority
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abu Dhabi Stem Cells Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
SYBRA is an open-label, phase 3, randomized controlled clinical trial that aims to assess the use of synovial biopsies in predicting response to biologic therapy in patients with rheumatoid arthritis that have failed disease-modifying drugs. The project has the potential to help change the current practice by offering the best treatment option. The decision to choose the best treatment for a particular patient is especially important in the context of the growing number of therapies available as a first-line option and the lack of specific biomarkers to predict response to treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Synovial biopsy, Biologic therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A (Anti-TNF)
Arm Type
Experimental
Arm Description
Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the diffuse myeloid phenotype will be assigned to receive anti-TNF medication at the discretion of the treating physician.
Arm Title
Group B (JAK inhibitor)
Arm Type
Experimental
Arm Description
Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the lymphoid- myeloid phenotype will be assigned to receive JAK inhibitor medication at the discretion of the treating physician.
Arm Title
Group C (Anti-TNF or JAK inhibitor)
Arm Type
Experimental
Arm Description
Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the pauci-cellular phenotype will be randomized to either anti-TNF or JAK inhibitor medication 1:1.
Intervention Type
Drug
Intervention Name(s)
Anti-TNF
Other Intervention Name(s)
Adalimumab, etanercept, certolizumab, or golimumab
Intervention Description
Upon analysis of the sample, patients that are falling into specific phenotypes (diffuse myeloid or pauci-cellular phenotypes) will be assigned to receive anti-TNF as biologic DMARD medications.
Intervention Type
Drug
Intervention Name(s)
JAK inhibitor
Other Intervention Name(s)
Tofacitinib, baricitinib, or upadacitinib
Intervention Description
Upon analysis of the sample, patients that are falling into specific phenotypes (lymphoid- myeloid or pauci-cellular phenotypes) will be assigned to receive JAK inhibitors as biologic DMARD medications.
Primary Outcome Measure Information:
Title
Change in DAS28 score
Description
Change in DAS28 score indicating remission compared to baseline in at least 50% of patients, where DS28<2.6 indicated remission. * DAS score: disease activity score, where <2.6 indicates remission, 2.6-3.2 low disease activity. 3.2-5.1 moderate disease activity; >5.1 high disease activity; higher values suggest worse outcomes.
Time Frame
Baseline, Visit 3 (12 weeks)
Secondary Outcome Measure Information:
Title
Change in HAQ score
Description
Significant decrease in HAQ score compared to baseline. * HAQ (Health assessment questionnaire). Scores vary from 0-to 3. Higher scores are associated with worse outcomes.
Time Frame
Baseline, Visit 3 (12 weeks)
Title
Change in power Doppler activity
Description
Change in power Doppler activity compared to a baseline where no power Doppler activity indicates remission. Measurement in Doppler activity on ultrasound using a grading system developed by EULAR. * Global EULAR-OMERACT Synovitis Score: scores range from 0-3 for each scanned joint. Higher scores correlate with worse outcomes.
Time Frame
Baseline, Visit 3 (12 weeks)
Title
Change in cellular phenotype
Description
Change in cellular phenotype compared to baseline. Estimation of change in the number of inflammatory cells as per the grading criteria.
Time Frame
Baseline, Visit 3 (12 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject should be capable of consent Age 18 and older Classified as rheumatoid arthritis as per EULAR/ACR criteria 2010 Failed one DMARD (Methotrexate, leflunomide, Sulfalsalazine, hydroxychloroquine) Can be on steroid dose <7.5mg Quantiferon negative Hepatitis B, C negative No recent history (<5y) of malignancy Exclusion Criteria: Overlap syndrome Previously treated with a biological medication Heart failure NYHA III/IV Active tuberculosis Active infections Previous history of DVT, PE, or Stroke Other significant comorbidities that will prevent them from taking any biologic medication as per EULAR guidelines on treating rheumatoid arthritis 2020. Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gianina Statache, MD
Organizational Affiliation
Abu Dhabi Stem Cells Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rene A. Rivero Jimenez, PhD
Organizational Affiliation
Abu Dhabi Stem Cells Center
Official's Role
Study Chair
Facility Information:
Facility Name
Abu Dhabi Stem Cells Center
City
Abu Dhabi
ZIP/Postal Code
4600
Country
United Arab Emirates

12. IPD Sharing Statement

Plan to Share IPD
No

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The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients

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