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

March 13, 2023 updated by: Abu Dhabi Stem Cells Center
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A (Anti-TNF)
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.
Drug: Anti-TNF
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.
Other Names:
  • Adalimumab, etanercept, certolizumab, or golimumab
Experimental: Group B (JAK inhibitor)
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.
Drug: JAK inhibitor
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.
Other Names:
  • Tofacitinib, baricitinib, or upadacitinib
Experimental: Group C (Anti-TNF or JAK inhibitor)
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.
Drug: Anti-TNF
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.
Other Names:
  • Adalimumab, etanercept, certolizumab, or golimumab
Drug: JAK inhibitor
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.
Other Names:
  • Tofacitinib, baricitinib, or upadacitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in DAS28 score
Time Frame: Baseline, Visit 3 (12 weeks)

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.
Baseline, Visit 3 (12 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HAQ score
Time Frame: Baseline, Visit 3 (12 weeks)

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.
Baseline, Visit 3 (12 weeks)
Change in power Doppler activity
Time Frame: Baseline, Visit 3 (12 weeks)

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.
Baseline, Visit 3 (12 weeks)
Change in cellular phenotype
Time Frame: Baseline, Visit 3 (12 weeks)
Change in cellular phenotype compared to baseline. Estimation of change in the number of inflammatory cells as per the grading criteria.
Baseline, Visit 3 (12 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abu Dhabi Stem Cells Center

Investigators

  • Principal Investigator: Gianina Statache, MD, Abu Dhabi Stem Cells Center
  • Study Chair: Rene A. Rivero Jimenez, PhD, Abu Dhabi Stem Cells Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2022

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

April 1, 2024

Study Registration Dates

First Submitted

May 12, 2022

First Submitted That Met QC Criteria

May 17, 2022

First Posted (Actual)

May 18, 2022

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT.006.1.1.SYBRA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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