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

NCT05379322 | Withdrawn Phase 3 DMC

• 1 other identifier: CT.006.1.1.SYBRA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Synovial biopsy; Biologic therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Visit 3 (12 weeks)

Secondary Outcomes (3)

• Change in HAQ score

  Baseline, Visit 3 (12 weeks)

• Change in power Doppler activity

  Baseline, Visit 3 (12 weeks)

• Change in cellular phenotype

  Baseline, Visit 3 (12 weeks)

Study Arms (3)

Group A (Anti-TNF)

EXPERIMENTAL

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

Group B (JAK inhibitor)

EXPERIMENTAL

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

Group C (Anti-TNF or JAK inhibitor)

EXPERIMENTAL

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; Drug: JAK inhibitor

Interventions

Anti-TNF DRUG

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.

Also known as: Adalimumab, etanercept, certolizumab, or golimumab

Group A (Anti-TNF); Group C (Anti-TNF or JAK inhibitor)

JAK inhibitor DRUG

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.

Also known as: Tofacitinib, baricitinib, or upadacitinib

Group B (JAK inhibitor); Group C (Anti-TNF or JAK inhibitor)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abu Dhabi Stem Cells Center: lead

Study Sites (1)

Abu Dhabi Stem Cells Center

Abu Dhabi, Abu Dhabi Emirate, 4600, United Arab Emirates

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab; Etanercept; Certolizumab Pegol; golimumab; Janus Kinase Inhibitors; tofacitinib; baricitinib; upadacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Gianina Statache, MD

  Abu Dhabi Stem Cells Center

  PRINCIPAL INVESTIGATOR

• Rene A. Rivero Jimenez, PhD

  Abu Dhabi Stem Cells Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: May 18, 2022
• Study Start: March 1, 2023
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: October 6, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)