Capability of Tofacitinib or Etanercept to Accelerate Tapering of NSAID and Treat-to-target Guided De-escalation of Corticosteroids in RA Patients

NCT04485325 | Completed Phase 4

• 1 other identifier: TMP-0731-2018
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 6

Brief Summary

Patients with active rheumatic arthritis (RA) and lack of efficacy of at least one csDMARD (Disease-modifying anti-rheumatic drug) treatment will be randomized to receive either Tofacitinib (TOFA) or etanercept (ETA). The study will be separated into two parts: The capability to decrease and discontinue pain-reducing treatment with a NSAID (non-steroidal anti-inflammatory drug) over the first 12 weeks of treatment will be measured for primary outcome measured using a visual analogue scale (VAS) at week 12 compared to baseline between the two treatment groups. Starting at week 12, the capability to taper corticosteroid (CS) treatment using a treat-to-target strategy, i.e. when at least low disease activity (LDA-DAS28) is achieved, will be measured in both groups.

Conditions

Rheumatic Arthritis

Keywords

treat-to-target; pain

Outcome Measures

Primary Outcomes (1)

• Discontinuation of Celecoxib treatment and clinically relevant improvement in pain

  Proportion of patients who can discontinue Celecoxib treatment and in whom clinically relevant improvement in pain levels are measured, defined as reduction in VAS pain of ≥ 30%

  Baseline to week 12

Secondary Outcomes (145)

• Mean dosage of Celecoxib in patients

  at 12 weeks

• discontinuation of CS-treatment

  at week 24

• rescue treatment

  at week 12

• Mean dosage of Corticosteroids (CS) in the patients who achieve Low Disease activity (LDA) in the two treatment groups

  at week 24

• Mean dosage of Corticosteroids (CS)

  at week 24

Study Arms (2)

Tofacitinib

ACTIVE COMPARATOR

Tofacitinib (Xeljanz®; 5 mg twice daily, p.o.)

Drug: Tofacitinib

Etanercept

ACTIVE COMPARATOR

Etanercept (Enbrel®; 50 mg once per week, s.c.)

Biological: Etanercept

Interventions

Tofacitinib DRUG

5 mg twice daily, p.o.

Also known as: TOFA, Xeljanz

Tofacitinib

Etanercept BIOLOGICAL

50 mg once per week, s.c.

Also known as: Enbrel, ETA

Etanercept

Eligibility Criteria

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

You may qualify if:

• Patients with active RA and an inadequate response to up to two previous conventional synthetic Disease modifying anti-rheumatic drug (csDMARD) treatments (methotrexate (MTX), leflunomide (LEF),sulfasalazine (SSZ)) with or without ongoing csDMARD therapy
• RA according to ACR classification criteria
• Age 18 - 65 years
• Active RA is defined as
• DAS28 \> 3.2 and
• TJC ≥ 3 and SJC ≥ 3
• VAS-pain ≥ 60 mm (0-100 mm)
• Accompanying CS treatment for RA with a stable dosage of ≥ 2mg/d and ≤ 10 mg/d 2 weeks prior to BL (not more than 30% of patients without CS)
• Accompanying need of NSAID or analgesic treatment due to arthritis and in dosages not exceeding the maximum dose according to Summary of Product characteristics (SmPC)
• If ongoing csDMARD treatment, stable treatment will be defined as either
• MTX treatment with a dosage of ≥ 10 mg/week and ≤ 25 mg/week, continuously for at least 12 weeks prior to Screening (SCR) with a stable dose of MTX for at least 2 weeks prior to BL or
• LEF treatment with a dosage between 10 to 20 mg/day, continuously for at least 12 weeks prior to SCR with a stable dose of LEF for at least 2 weeks prior to BL or
• SSZ treatment with dosage between 1 to 3 g/day, continuously for at least 12 weeks prior to SCR with a stable dose of SSZ for at least 2 weeks prior to BL
• Presence of documented negative results for testing of Hepatitis B and C
• Completed SARS-CoV-2-immunisation as currently recommended by the Standing Committee of Vaccination

You may not qualify if:

• Previous use of Tofacitinib or other Janus-Kinase (JAK)-inhibitors
• Previous use of Etanercept
• Previous use of any biological agent for RA
• which was stopped due to lack of efficacy
• one previous use of biological stopped due to intolerance will be allowed
• CS treatment with dosages \>10 mg at BL
• Known hypersensitivity to any component of the study medication (TOFA, ETA, Celecoxib)
• Previous use of Celecoxib as analgesic therapy which was stopped due to lack of efficacy or intolerance
• Patients with other chronic inflammatory articular disease or systemic autoimmune disease
• Patients with active Tuberculosis (Tb) (evaluation of Tb according to local standards in clinical care)
• Patients with latent Tb, that are not pre-treated for at least 1 month and planned to be treated 9 months in total with Isozid once a day
• Any active infection, a history of recurrent clinically significant infections (e.g. human immune deficiency virus (HIV)), or a history of recurrent bacterial infections with encapsulated organisms
• Primary or secondary immunodeficiency
• Current malignancy or history of malignancies except adequately treated or excised basal cell or squamous cell carcinoma or cervical carcinoma in situ.
• Patients of 50 years and older, if they have one or more cardiovascular risk factors (CVRF) defined as:

Sponsors & Collaborators

• Dr. Frank Behrens: lead
• Pfizer: collaborator

Study Sites (6)

Charité Universitätsmedizin Berlin, Med. Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie

Berlin, Germany

Location

Rheumatologische Schwerpunktpraxis im Ärztehaus am Walter-Schreiber-Platz

Berlin, Germany

Location

CIRI - Centrum für innovative Diagnostik & Therapie, Rheumatologie/ Immunologie GmbH

Frankfurt, Germany

Location

Katholische Kliniken Rhein-Ruhr, St. Elisabeth Gruppe GmbH, Rheumazentrum Ruhrgebiet

Herne, Germany

Location

Praxis Prof. Dr. Kellner

München, Germany

Location

Rheumazentrum Ratingen

Ratingen, Germany

Location

MeSH Terms

Conditions

Rheumatic Fever; Pain

Interventions

tofacitinib; 5-(tetradecyloxy)-2-furancarboxylic acid; Etanercept; Receptor, Endothelin A

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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; Receptors, Endothelin; Receptors, G-Protein-Coupled; Receptors, Peptide

Study Officials

• Harald Burkhardt, MD

  Fraunhofer IME

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Representative of the Sponsor

Model Details: two arm, randomized, open-label, parallel group

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: July 24, 2020
• Study Start: November 4, 2019
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

DE (6)