Rheumatic ArthritisPhase 4AcceleRAteNCT04485325
Capability of Tofacitinib or Etanercept to Accelerate Tapering of NSAID and Treat-to-target Guided De-escalation of Corticosteroids in RA Patients
A Phase 4 study testing Tofacitinib and Etanercept in people with Rheumatic Arthritis, run by Dr. Frank Behrens at 6 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatic Arthritis
- What is being tested?
- Tofacitinib and Etanercept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 6 sitesGermany
- Study dates
- 4 Nov 2019to 31 Mar 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Written informed consent obtained prior to the initiation of any protocol-required procedures
- Willingness to comply to study procedures and study protocol
Who cannot join
- 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
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- 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
- 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:
- Current cigarette smoking,
- Known diagnosis of hypertension,
- HDL <40 mg/dl,
- Diabetes mellitus,
- History of coronary artery disease: history of revascularization procedure, coronary artery bypass grafting, myocardial infarction, cardiac arrest, unstable angina, acute coronary syndrome or
- History of premature coronary heart disease or sudden death documented in first degree relatives (male relative before 55 years, female relative before 65 years)
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Charité Universitätsmedizin Berlin, Med. Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie
Berlin
Rheumatologische Schwerpunktpraxis im Ärztehaus am Walter-Schreiber-Platz
Berlin
CIRI - Centrum für innovative Diagnostik & Therapie, Rheumatologie/ Immunologie GmbH
Frankfurt
Katholische Kliniken Rhein-Ruhr, St. Elisabeth Gruppe GmbH, Rheumazentrum Ruhrgebiet
Herne
Praxis Prof. Dr. Kellner
München
Rheumazentrum Ratingen
Ratingen
About this study
Official title: 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)
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.
Read the 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.
- Conditions
- Rheumatic Arthritis
- Being tested
- Tofacitinib, Etanercept
- Keywords
- treat-to-target, pain
- Medical subject headings
- Rheumatic Fever, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofacitinibDrug
Also called TOFA, Xeljanz
5 mg twice daily, p.o.
EtanerceptBiological
Also called Enbrel, ETA
50 mg once per week, s.c.
| Study group | Role | What they receive |
|---|---|---|
| Tofacitinib | Active comparator | Tofacitinib (Xeljanz®; 5 mg twice daily, p.o.) Receives: Drug: Tofacitinib |
| Etanercept | Active comparator | Etanercept (Enbrel®; 50 mg once per week, s.c.) Receives: Biological: Etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: Baseline to week 12
Secondary outcomes (145)
Mean dosage of Celecoxib in patients
Mean dosage of Celecoxib in patients
Measured: at 12 weeks
discontinuation of CS-treatment
Proportion of patients with discontinuation of CS-treatment at week 24
Measured: at week 24
rescue treatment
Proportion of patients who require rescue treatment at week 12
Measured: at week 12
Mean dosage of Corticosteroids (CS) in the patients who achieve Low Disease activity (LDA) in the two treatment groups
Mean dosage of CS in the patients who achieve LDA at week 24 in the two treatment groups
Measured: at week 24
Mean dosage of Corticosteroids (CS)
Mean dosage of CS at week 24 (W24)
Measured: at week 24
NSAID treatment
Number of patients with NSAID treatment at W24
Measured: at week 24
re-started NSAID treatment
Proportion of patients who re-started NSAID treatment after week 12 (W12) until W24
Measured: week 12 to week 24
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 2
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 4
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 8
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 12
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 16
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 20
Absolute pain levels
Absolute pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 24
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 2
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 4
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 8
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 12
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 16
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 20
relative (percent) pain levels
relative (percent) pain levels measured by visual analogue scale (VAS). minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 24
Change in pain levels
Change in pain levels measured by visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 2
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 4
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 8
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 12
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 16
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 20
Change in pain levels
Change in pain levels visual analogue scale (VAS) compared to BL. minimum is 0 mm, maximum is 100 mm whereas 0 is no pain and 100 is worst
Measured: at week 24
Determination of flares
Determination of flares (measured by FLARE questionnaire) between week 12 and week 24
Measured: between week 12 and week 24
Proportion of LDA
Proportion of patients who achieve LDA (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) (DAS28 (ESR) ≤ 3.2)
Measured: at week 4
Proportion of LDA
Proportion of patients who achieve LDA (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) (DAS28 (ESR) ≤ 3.2)
Measured: at week 12
Proportion of LDA
Proportion of patients who achieve LDA (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) (DAS28 (ESR) ≤ 3.2)
Measured: at week 16
Proportion of LDA
Proportion of patients who achieve LDA (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) (DAS28 (ESR) ≤ 3.2)
Measured: at week 20
Proportion of LDA
Proportion of patients who achieve LDA (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) (DAS28 (ESR) ≤ 3.2)
Measured: at week 24
Proportion of DAS remission
Proportion of patients who achieve DASremission (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) DAS28 (ESR) ≤ 2.6)
Measured: at week 4
Proportion of DAS remission
Proportion of patients who achieve DASremission (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) DAS28 (ESR) ≤ 2.6)
Measured: at week 12
Proportion of DAS remission
Proportion of patients who achieve DASremission (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) DAS28 (ESR) ≤ 2.6)
Measured: at week 16
Proportion of DAS remission
Proportion of patients who achieve DASremission (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) DAS28 (ESR) ≤ 2.6)
Measured: at week 20
Proportion of DAS remission
Proportion of patients who achieve DASremission (Disease Activity Score 28 (DAS28) calculated by Erythrocyte sediment rate (ESR) DAS28 (ESR) ≤ 2.6)
Measured: at week 24
Proportion of ACR20 response
Proportion of patients who achieve ACR20 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 20%
Measured: at week 4
Proportion of ACR20 response
Proportion of patients who achieve ACR20 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 20%
Measured: at week 12
Proportion of ACR20 response
Proportion of patients who achieve ACR20 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 20%
Measured: at week 16
Proportion of ACR20 response
Proportion of patients who achieve ACR20 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 20%
Measured: at week 20
Proportion of ACR20 response
Proportion of patients who achieve ACR20 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 20%
Measured: at week 24
Proportion of ACR 50 response
Proportion of patients who achieve ACR50 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 50%
Measured: at week 4
Proportion of ACR 50 response
Proportion of patients who achieve ACR50 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 50%
Measured: at week 12
Proportion of ACR 50 response
Proportion of patients who achieve ACR50 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 50%
Measured: at week 16
Proportion of ACR 50 response
Proportion of patients who achieve ACR50 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 50%
Measured: at week 20
Proportion of ACR 50 response
Proportion of patients who achieve ACR50 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 50%
Measured: at week 24
Proportion of ACR 70 response
Proportion of patients who achieve ACR70 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 70%
Measured: at week 4
Proportion of ACR 70 response
Proportion of patients who achieve ACR70 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 70%
Measured: at week 12
Proportion of ACR 70 response
Proportion of patients who achieve ACR70 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 70%
Measured: at week 16
Proportion of ACR 70 response
Proportion of patients who achieve ACR70 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 70%
Measured: at week 20
Proportion of ACR 70 response
Proportion of patients who achieve ACR70 response - measure based on American College of Rheumatology (ACR) criteria improvement of at least 70%
Measured: at week 24
Changes in ACR core set
Changes in ACR core set
Measured: at baseline
Changes in ACR core set
Changes in ACR core set
Measured: at week 4
Changes in ACR core set
Changes in ACR core set
Measured: at week 12
Changes in ACR core set
Changes in ACR core set
Measured: at week 16
Changes in ACR core set
Changes in ACR core set
Measured: at week 20
Changes in ACR core set
Changes in ACR core set change
Measured: at week 24
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at baseline
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at week 4
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at week 12
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at week 16
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at week 20
DAS28 (ESR)
DAS28 (ESR) change compared to BL
Measured: at week 24
SJC (66),
Swollen joint count (66 joints) change compared to BL
Measured: at baseline
SJC (66),
Swollen joint count (66 joints) change compared to BL
Measured: at week 4
SJC (66),
Swollen joint count (66 joints) change compared to BL
Measured: at week 12
SJC (66),
Swollen joint count (66 joints) change compared to BL
Measured: at week 16
SJC (66),
Swollen joint count (66 joints) change compared to BL
Measured: at week 20
SJC (66),
Swollen joint count (SJC) (66 joints) change compared to BL
Measured: at week 24
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at baseline
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at week 4
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at week 12
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at week 16
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at week 20
TJC (68)
tender joint count (TJC) - 68 joints change compared to BL
Measured: at week 24
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores
Measured: at baseline
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores.SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 4
Change in Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 change to BL. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 4
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 12
Change in Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 change to BL. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 12
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 16
Change in Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 change to BL. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 16
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 20
Change in Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 change to BL. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 20
Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 scores. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 24
Change in Quality of Life: SF36 (36 items short form health survey)
Quality of Life: SF36 change to BL. SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at week 24
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at baseline
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 4
Change in Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI change to BL. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 4
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 12
Change of Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI change to BL. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 12
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 16
Change of Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI change to BL. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 16
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores.The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 20
Change of Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI change to BL. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 20
Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI scores. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 24
Change of Quality of Life HAQ-DI (health assessment questionnaire - disability index)
Quality of Life HAQ-DI change to BL. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do).
Measured: at week 24
Correlation of SF36 and HAQ-DI results
Correlation of SF36 and HAQ-DI results. The HAQ-DI is a health assessment questionnaire - disability index that consists of 8 subcategories. For each the single scales range from 0 (no difficulty) to 3 (unable to do). SF36 is a 36 items short form health survey and consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: through study completion, an average of 24 weeks
Treatment satisfaction: TSQM-14 scores
Treatment Satisfaction Questionnaire for Medication (TSQM-14) scores. The TSQM items are answered on 5- or 7-point Likert type scale and cover four domains: effectiveness; side effects; convenience and global satisfaction. A score can be obtained for each domain by summing of the corresponding items transformed on a 0-100 scale; higher values indicate higher satisfaction, better perceived effectiveness, lower burden associated to side-effects, better convenience.
Measured: at week 4
Treatment satisfaction: TSQM-14 scores
Treatment Satisfaction Questionnaire for Medication (TSQM-14) scores. The TSQM items are answered on 5- or 7-point Likert type scale and cover four domains: effectiveness; side effects; convenience and global satisfaction. A score can be obtained for each domain by summing of the corresponding items transformed on a 0-100 scale; higher values indicate higher satisfaction, better perceived effectiveness, lower burden associated to side-effects, better convenience.
Measured: at week 12
Treatment satisfaction: TSQM-14 scores
Treatment Satisfaction Questionnaire for Medication (TSQM-14) scores. The TSQM items are answered on 5- or 7-point Likert type scale and cover four domains: effectiveness; side effects; convenience and global satisfaction. A score can be obtained for each domain by summing of the corresponding items transformed on a 0-100 scale; higher values indicate higher satisfaction, better perceived effectiveness, lower burden associated to side-effects, better convenience.
Measured: at week 16
Treatment satisfaction: TSQM-14 scores
Treatment Satisfaction Questionnaire for Medication (TSQM-14) scores. The TSQM items are answered on 5- or 7-point Likert type scale and cover four domains: effectiveness; side effects; convenience and global satisfaction. A score can be obtained for each domain by summing of the corresponding items transformed on a 0-100 scale; higher values indicate higher satisfaction, better perceived effectiveness, lower burden associated to side-effects, better convenience.
Measured: at week 24
Patient's expectation on treatment
Patient's expectation on treatment asked and documented as free text
Measured: at baseline
Patient's expectation on treatment
Patient's expectation on treatment asked and documented as free text
Measured: at week 12
Patient's expectation on treatment
Patient's expectation on treatment asked and documented as free text
Measured: at week 24
Correlation of TSQM-14 results and patient's expectation on treatment
Correlation of TSQM-14 results and patient's expectation on treatment
Measured: through study completion, an average of 24 weeks
drug accountability
Evaluation of results of treatment adherence (drug accountability) using patient diary
Measured: at week 4
drug accountability
Evaluation of results of treatment adherence (drug accountability) using patient diary
Measured: at week 12
drug accountability
Evaluation of results of treatment adherence (drug accountability) using patient diary
Measured: at week 16
drug accountability
Evaluation of results of treatment adherence (drug accountability) using patient diary
Measured: at week 20
drug accountability
Evaluation of results of treatment adherence (drug accountability) using patient diary
Measured: at week 24
eGFR (estimated glomerular filtration rate)
eGFR value
Measured: at baseline
eGFR (estimated glomerular filtration rate)
eGFR value
Measured: at week 4
change in eGFR (estimated glomerular filtration rate)
eGFR change to BL
Measured: at week 4
eGFR (estimated glomerular filtration rate)
eGFR value
Measured: at week 12
change in eGFR (estimated glomerular filtration rate)
eGFR change to BL
Measured: at week 12
change in eGFR (estimated glomerular filtration rate)
eGFR change to BL
Measured: at week 16
eGFR (estimated glomerular filtration rate)
eGFR value
Measured: at week 16
change in eGFR (estimated glomerular filtration rate)
eGFR change to BL
Measured: at week 20
eGFR (estimated glomerular filtration rate)
eGFR value
Measured: at week 24
change in eGFR (estimated glomerular filtration rate)
eGFR change to BL
Measured: at week 24
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at baseline
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at week 4
change in blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure change to BL
Measured: at week 4
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at week 12
change in blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure change to BL
Measured: at week 12
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at week 16
change in blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure change to BL
Measured: at week 16
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at week 20
change in blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure change to BL
Measured: at week 20
blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure
Measured: at week 24
change in blood pressure (mmHg)
blood pressure (mmHg) Systolic or Diastolic Blood Pressure change to BL
Measured: at week 24
pain characteristics measured by QST (quantitative sensory testing)
Correlation of pain characteristics measured by QST, VAS pain and pain relief
Measured: at Baseline
pain characteristics measured by QST (quantitative sensory testing)
Correlation of pain characteristics measured by QST, VAS pain and pain relief
Measured: at week 4
pain characteristics measured by QST (quantitative sensory testing)
Correlation of pain characteristics measured by QST, VAS pain and pain relief
Measured: at week 8
pain characteristics measured by QST (quantitative sensory testing)
Correlation of pain characteristics measured by QST, VAS pain and pain relief
Measured: at week 12
pain characteristics measured by QST (quantitative sensory testing)
Correlation of pain characteristics measured by QST, VAS pain and pain relief
Measured: at week 24
adverse events (AEs)
Documentation of type, frequency and seriousness of adverse events (AEs)
Measured: through study completion, an average of 24 weeks
Infections
Incidence rates of serious infection events (SIEs),
Measured: through study completion, an average of 24 weeks
Documentation of all lab abnormalities
incidence rates of lab abnormalities
Measured: through study completion, an average of 24 weeks
Cardiovascular events
incidence rates of cardio vascular events
Measured: through study completion, an average of 24 weeks
Malignencies
incidence rates of malignancies
Measured: through study completion, an average of 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start4 Nov 2019
- Primary completion31 Mar 2024
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatic ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- two arm, randomized, open-label, parallel group
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Frank Behrens
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, Dr. Frank Behrens, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Investigators
- Harald Burkhardt, MD, Principal investigator, Fraunhofer IME
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04485325
- Sponsor's protocol ID
- TMP-0731-2018
- Acronym
- AcceleRAte
- Status last verified
- Aug 2024
- First submitted
- 30 Apr 2020
- Last updated
- 28 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04485325
- Acronym / sponsor ID
- AcceleRAte / TMP-0731-2018
- Conditions
- Rheumatic Arthritis
- Keywords
- treat-to-target, pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Dr. Frank BehrensUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 24 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- two arm, randomized, open-label, parallel group
| Arm | Type | Receives |
|---|---|---|
| Tofacitinib | Active comparator | Drug: TofacitinibTofacitinib (Xeljanz®; 5 mg twice daily, p.o.) |
| Etanercept | Active comparator | Biological: EtanerceptEtanercept (Enbrel®; 50 mg once per week, s.c.) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- VAS-pain ≥ 60 mm (0-100 mm)
Key exclusion criteria (37 listed)
- Previous use of Tofacitinib or other Janus-Kinase (JAK)-inhibitors
- Previous use of Etanercept
- Previous use of any biological agent for RA
- CS treatment with dosages >10 mg at BL
- Known hypersensitivity to any component of the study medication (TOFA, ETA, Celecoxib)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TofacitinibAlso: TOFA, Xeljanz5 mg twice daily, p.o. | Drug | Tofacitinib |
| EtanerceptAlso: Enbrel, ETA50 mg once per week, s.c. | Biological | Etanercept |
Primary outcome
Discontinuation of Celecoxib treatment and clinically relevant improvement in pain
Time frame: Baseline to week 12
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%
145 secondary outcomes
Mean dosage of Celecoxib in patients
Time frame: at 12 weeks
discontinuation of CS-treatment
Time frame: at week 24
rescue treatment
Time frame: at week 12
Mean dosage of Corticosteroids (CS) in the patients who achieve Low Disease activity (LDA) in the two treatment groups
Time frame: at week 24
Mean dosage of Corticosteroids (CS)
Time frame: at week 24
NSAID treatment
Time frame: at week 24
re-started NSAID treatment
Time frame: week 12 to week 24
Absolute pain levels
Time frame: at week 2
Absolute pain levels
Time frame: at week 4
Absolute pain levels
Time frame: at week 8
Absolute pain levels
Time frame: at week 12
Absolute pain levels
Time frame: at week 16
Absolute pain levels
Time frame: at week 20
Absolute pain levels
Time frame: at week 24
relative (percent) pain levels
Time frame: at week 2
relative (percent) pain levels
Time frame: at week 4
relative (percent) pain levels
Time frame: at week 8
relative (percent) pain levels
Time frame: at week 12
relative (percent) pain levels
Time frame: at week 16
relative (percent) pain levels
Time frame: at week 20
relative (percent) pain levels
Time frame: at week 24
Change in pain levels
Time frame: at week 2
Change in pain levels
Time frame: at week 4
Change in pain levels
Time frame: at week 8
Change in pain levels
Time frame: at week 12
Change in pain levels
Time frame: at week 16
Change in pain levels
Time frame: at week 20
Change in pain levels
Time frame: at week 24
Determination of flares
Time frame: between week 12 and week 24
Proportion of LDA
Time frame: at week 4
Proportion of LDA
Time frame: at week 12
Proportion of LDA
Time frame: at week 16
Proportion of LDA
Time frame: at week 20
Proportion of LDA
Time frame: at week 24
Proportion of DAS remission
Time frame: at week 4
Proportion of DAS remission
Time frame: at week 12
Proportion of DAS remission
Time frame: at week 16
Proportion of DAS remission
Time frame: at week 20
Proportion of DAS remission
Time frame: at week 24
Proportion of ACR20 response
Time frame: at week 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harald Burkhardt, MD principal investigator
Fraunhofer IME
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tofacitinib and Etanercept in people with Rheumatic Arthritis, run by Dr. Frank Behrens at 6 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Discontinuation of Celecoxib treatment and clinically relevant improvement in pain (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.