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

NCT04485325

Last updated date
Study Location
Charité Universitätsmedizin Berlin, Med. Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie
Berlin, , , Germany
Contact
00 49 69 6301

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

00 49 69 6301

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Rheumatic Arthritis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-65 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

- Written informed consent obtained prior to the initiation of any protocol-required procedures

- Willingness to comply to study procedures and study protocol

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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


- Concomitant diseases with chronic pain syndrome or need of extended dosages or
long-term treatment with the maximum dosages of NSAID/analgesics (according to SmPC)
due to other concomitant diseases/pain symptoms in discretion of the treating
physician Exclusion criteria related to general health


- 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


- History of cancer with curative treatment not longer than 5 years ago except
basal-cell carcinoma of the skin that had been excised


- Evidence of significant uncontrolled concomitant diseases or serious and/or
uncontrolled diseases that are likely to interfere with the evaluation of the
patient's safety and with the study outcome


- History of a severe psychological illness or condition


- Known hypersensitivity to sulfonamides


- Active peptic ulceration or gastrointestinal (GI) bleeding


- Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic
oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid
(aspirin) or other NSAIDs including Cyclooxigenase (COX)-2 inhibitors


- Risk for or history of thrombotic events (e.g. pulmonary embolism or thrombosis)
Severe hepatic dysfunction (serum albumin < 25 g/L or Child-Pugh score ≥ 10)


- Patients with estimated creatinine clearance < 30 mL/min


- Inflammatory bowel disease


- Congestive heart failure (New York Heart Association (NYHA) II-IV)


- Established ischaemic heart disease, peripheral arterial disease and/or
cerebrovascular disease


- Women lactating, pregnant, nursing or of childbearing potential with a positive
pregnancy test


- Males or females of reproductive potential not willing to use effective contraception
(e.g. contraceptive pill, intrauterine device (IUD), physical barrier)


- Alcohol, drug or chemical abuse Exclusion criteria related to prior treatments


- Current participation in another interventional clinical trial or participation within
the last 90 days Exclusion criteria related to formal aspects


- Underage or incapable patients

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Rheumatic ArthritisCapability of Tofacitinib or Etanercept to Accelerate Tapering of NSAID and Treat-to-target Guided De-escalation of Corticosteroids in RA Patients
NCT04485325
  1. Berlin,
  2. Berlin,
  3. Frankfurt,
  4. Herne,
  5. München,
  6. Ratingen,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Capability of Tofacitinib or Etanercept to Accelerate Tapering of NSAID and Treat-to-target Guided De-escalation of Corticosteroids in RA Patients
Official Title  ICMJE Capability of Tofacitinib or Etanercept to Accelerate Clinical Relevant Tapering of Non-steroidal Anti-inflammatory Drugs (NSAID) and Treat-to-target Guided De-escalation of Corticosteroids in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Previous csDMARD Therapy (AcceleRAte)
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.

Detailed Description

In this clinical study, a design was chosen to reflect European standards recommended by EULAR for treatment of active RA by comparison of a Treat-to- target (T2T) approach in two treatment groups: Patients with active RA and lack of efficacy of at least one csDMARD treatment will be randomized to receive either TOFA or ETA. The study will be separated into two parts: The capability to decrease and discontinue pain-reducing treatment with a NSAID (Celecoxib, two times 200 mg as maximum standard dosage for RA) over the first 12 weeks of treatment will be measured for primary outcome. The proportion of patients with successful discontinuation of Celecoxib and significant and clinical relevant decrease of pain-levels measured using a visual analogue scale (VAS) with a reduction of at least 30% at week 12 compared to baseline will be compared between the two treatment groups.

Starting at week 12, the capability to taper 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. In addition to efficacy assessments (DAS28, ACR-response, SJC, TJC), patient reported outcomes, Quality of Life (QoL) measurements and patient satisfaction will be evaluated. Safety (severity and frequency of adverse events) will be evaluated over the 24-week treatment period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
two arm, randomized, open-label, parallel group
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatic Arthritis
Intervention  ICMJE
  • Drug: Tofacitinib
    5 mg twice daily, p.o.
    Other Name: TOFA, Xeljanz
  • Biological: Etanercept
    50 mg once per week, s.c.
    Other Name: Enbrel, ETA
Study Arms  ICMJE
  • Active Comparator: Tofacitinib
    Tofacitinib (Xeljanz®; 5 mg twice daily, p.o.)
    Intervention: Drug: Tofacitinib
  • Active Comparator: Etanercept
    Etanercept (Enbrel®; 50 mg once per week, s.c.)
    Intervention: Biological: Etanercept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 22, 2020)
192
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • Written informed consent obtained prior to the initiation of any protocol-required procedures
  • Willingness to comply to study procedures and study protocol

Exclusion Criteria:

  • 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
  • Concomitant diseases with chronic pain syndrome or need of extended dosages or long-term treatment with the maximum dosages of NSAID/analgesics (according to SmPC) due to other concomitant diseases/pain symptoms in discretion of the treating physician Exclusion criteria related to general health
  • 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
  • History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
  • Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and with the study outcome
  • History of a severe psychological illness or condition
  • Known hypersensitivity to sulfonamides
  • Active peptic ulceration or gastrointestinal (GI) bleeding
  • Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid (aspirin) or other NSAIDs including Cyclooxigenase (COX)-2 inhibitors
  • Risk for or history of thrombotic events (e.g. pulmonary embolism or thrombosis) Severe hepatic dysfunction (serum albumin < 25 g/L or Child-Pugh score ? 10)
  • Patients with estimated creatinine clearance < 30 mL/min
  • Inflammatory bowel disease
  • Congestive heart failure (New York Heart Association (NYHA) II-IV)
  • Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
  • Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
  • Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, intrauterine device (IUD), physical barrier)
  • Alcohol, drug or chemical abuse Exclusion criteria related to prior treatments
  • Current participation in another interventional clinical trial or participation within the last 90 days Exclusion criteria related to formal aspects
  • Underage or incapable patients
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anja Kuehne00 49 69 6301 ext 80225[email protected]
Contact: Tanja Rossmanith, PhD[email protected]
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04485325
Other Study ID Numbers  ICMJE TMP-0731-2018
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Frank Behrens, Fraunhofer Institute for Molecular Biology and Applied Ecology
Study Sponsor  ICMJE Dr. Frank Behrens
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Harald Burkhardt, MDFraunhofer IME
PRS Account Fraunhofer Institute for Molecular Biology and Applied Ecology
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP