Targeted Treatment Early With Etanercept + Methotrexate vs.T2T Care for DMARD-naïve Early RA Patients Based on naïve T-cell Stratification

NCT03813771 | Unknown Phase 4 DMC

• 2 other identifiers: RR16/2092016-002344-16
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

The main aim of the study is to determine the clinical utility of naive T-cell stratification for rationalising treatment with methotrexate (MTX), for DMARD-naive early RA patients. Thus, it aims to determine whether TNFi therapy (Benepali) instituted as first-line therapy in DMARD-naive early RA patients with poor T-cell prognostication confers better outcomes (clinical, structural and immunological). Hence, this would enable early targeted treatment for those with a poorer prognosis based on their immunological status.

Conditions

Rheumatoid Arthritis

Keywords

T-cells; Treat to Target; DMARD-naive; Benepali

Outcome Measures

Primary Outcomes (1)

• Clinical Remission at 24 weeks (Arms A vs B)

  The difference in the proportions of patients in clinical remission (DAS28ESR ≤2.6) at 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies

  24 weeks

Secondary Outcomes (9)

• Clinical Remission at 12 weeks (Arms A vs B)

  12 weeks

• Clinical Remission at 12 and 24 weeks (Arms B vs C)

  12 and 24 weeks

• Sustained Clinical Remission

  12 and 24 weeks

• Patient Reported Outcomes at 12 and 24 weeks (Arm A vs B)

  12 and 24 weeks

• Patient Reported Outcomes at 12 and 24 weeks (Arm B vs C)

  12 and 24 weeks

Study Arms (3)

Abnormal T-cells: Benepali + T2T Care

EXPERIMENTAL

Treatment Arm C will receive Benepali and methotrexate combination therapy and followed as per T2T care over a total duration of 24 weeks. Sulfasalazine or Hydroxychloroquine may be added to therapy at follow up visits in-line with T2T care. Benepali will be administered subcutaneously at a dose of 50mg weekly and discontinued at the primary endpoint (24 weeks). Methotrexate will be administered orally at a starting dose of 15mg weekly. It may be increased in line with T2T care (to a maximum of 25mg) over the 24 weeks.

Drug: Benepali; Drug: Methotrexate

Abnormal T-cells: Methotrexate + T2T Care

ACTIVE COMPARATOR

Treatment Arm B will receive initial methotrexate monotherapy with adoption of a treat to target protocol (standard care involving monthly DAS28-ESR assessment with escalation to combination synthetic DMARD (Including sulfasalazine and/or hydroxychloroquine). therapy if not achieving low disease activity (LDA) at, or after, 8 weeks).

Drug: Sulfasalazine; Drug: Methotrexate; Drug: Hydroxychloroquine

Normal T-cells: Methotrexate + T2T Care

OTHER

Treatment Arm A will receive standard T2T care as per Arm B.

Drug: Sulfasalazine; Drug: Methotrexate; Drug: Hydroxychloroquine

Interventions

Benepali DRUG

Benepali will be adminstered subcutaneously at a dose of 50mg weekly and discontinued at the primary endpoint (24 weeks).

Also known as: Etanercept

Abnormal T-cells: Benepali + T2T Care

Sulfasalazine DRUG

Sulfasalazine will be added at follow up visits (T2T care) if the subject fails to achieve low disease activity,administered orally at a dose of 1g twice daily.

Abnormal T-cells: Methotrexate + T2T Care; Normal T-cells: Methotrexate + T2T Care

Methotrexate DRUG

Methotrexate will be administered orally at a starting dose of 15mg weekly. It may be increased in line with T2T care (to a maximum of 25mg) over the 24 weeks.

Abnormal T-cells: Benepali + T2T Care; Abnormal T-cells: Methotrexate + T2T Care; Normal T-cells: Methotrexate + T2T Care

Hydroxychloroquine DRUG

Hydroxychloroquine will be added at follow up visits (T2T care) if the subject fails to achieve low diseaseactivity, administered at a dose of 200mg daily.

Abnormal T-cells: Methotrexate + T2T Care; Normal T-cells: Methotrexate + T2T Care

Eligibility Criteria

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

You may qualify if:

• Subject has a diagnosis of RA as defined by the new ACR/EULAR 2010 classification criteria
• Newly diagnosed (within 12 weeks)
• Active disease at screening (DAS28ESR ≥3.2 or clinical evidence of synovitis)
• Anti-citrillunated protein antibody (ACPA) positive
• Male \& female subjects ≥18 years old
• DMARD (disease modifying anti-rheumatic drug) naïve
• No use of intra-muscular, intra-articular or oral corticosteroids 4 weeks days prior to screening
• All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.
• Patients must have the capacity and be willing to provide written informed consent and comply with the requirements of the protocol

You may not qualify if:

• Use of any additional investigational medications or products within 28 days of screening (including prior to screening)
• Use of intra-muscular/intra-articular or oral corticosteroids within 28 days prior to screening
• Use (including use as required) of more than one NSAID, change in NSAID or change in dose of NSAID within 28 days of the baseline visit.
• Live vaccine within \<28 days prior to screening
• Pregnant/lactating women or planning pregnancy within 24 weeks of last protocol treatment
• Planned surgery within the study period (requiring omission of study medication \> 28 days
• The presence of other comorbidities, which the physician deems as significant to interfere with evaluation (musculoskeletal condition such as osteoarthritis \& fibromyalgia)
• Diagnosis of another inflammatory arthritis or connective tissue disease (e.g. psoriatic arthritis or Ankylosing spondylitis, primary Sjogren's syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis)
• Concomitant severe infection requiring intravenous therapy 4 weeks (28) days prior to screening
• Any contraindication to conventional DMARD's/anti-TNF therapy
• Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by:
• Aminotransferase (AST) / alanine aminotransferase (ALT) \> 3x upper limit of normal (ULN) OR Bilirubin \> 50µmol/L
• Serum Creatinine \> 175 umol/L
• eGFR below 30ml/L/min/1.73m2
• neutrophils \< 2000 x 106/L

Sponsors & Collaborators

• University of Leeds: lead
• Samsung Bioepis Co., Ltd.: collaborator

Study Sites (1)

Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept; Sulfasalazine; Methotrexate; Hydroxychloroquine

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)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines

Study Officials

• Paul Emery, Professor

  Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Goulding

CONTACT

0113 392 4495; j.t.r.goulding@leeds.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, longitudinal cohort study with an embedded pilot randomised controlled trial. Patients with normal naive T-cell status will receive standard T2T care with methotrexate. Patients with abnormal naive T-cell status will be randomised 1:1 to T2T care vs. Benepali + T2T care with methotrexate

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: January 23, 2019
• Study Start: March 1, 2019
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: January 23, 2019

Record last verified: 2019-01

Locations

GB (1)