A Phase 4 interventional study of Benepali and Sulfasalazine in Rheumatoid Arthritis, sponsored by University of Leeds. Status unknown at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-01-23.
Sponsored by University of Leeds · Phase 4, Interventional, and Treatment
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.
The current optimal therapeutic approach in early RA is to start MTX to target inflammation and induce remission.Prediction of MTX therapy response remains a key clinical need to enable the identification of patients who would benefit from an alternative, more aggressive treatment strategy. Multiple predictors of remission with MTX have been reported over the years but none have entered routine clinical practice.
We previously reported that T-cell phenotyping at baseline could predict remission in DMARD-naïve early RA treated with MTX. Reduced naïve CD4+ T-cell frequency was the most predictive factor, using both a pilot and a replication cohort.These data confirmed the potential value of using naïve CD4+ T-cells as a biomarker of MTX induced remission in early RA.
The clinical utility of measuring T-cell subsets is therefore strongly indicated by these data and suggests that measurement of T- cell subsets can be used to rationalise the use of MTX as first-line therapy.Predicting response to MTX has important clinical value to identify patients who will do well on MTX but furthermore for directing those who will have a sub-optimal response to MTX to receive alternative therapy without any harmful delay and in line with the treat to target principle.
The current study aims to confirm/validate the clinical value of T-cell subset quantification for the prediction of MTX response in early RA, by stratified interventions based on baseline naïve CD4+ T-cell status.
This is a Single centre, phase IV, open-label, prospective, longitudinal cohort study with an embedded pilot randomised controlled trial that aims to assess whether MTX can be rationalised as a first-line treatment for DMARD-naïve early RA patients, according to baseline naïve CD4+ T-cell stratification.
Patients with newly diagnosed RA satisfying the inclusion criteria will be recruited from our early arthritis clinic. Eligible patients will be provided with written information on the study and will be given a minimum of 24 hours to read this information prior to being contacted by a research nurse (within one week). If interested they will be invited to a screening appointment within four weeks to confirm eligibility, obtain written consent and to collect the necessary clinical and laboratory data as per the study schedule. Following the screening visit, patients will attend a baseline assessment within four weeks.
Patients will be stratified based on their naïve CD4+ T-cell frequency (normal or abnormal based on our pre-defined cut-off values according to age and sex-matched controls). Patients with a normal T-cell frequency (Arm A) will commence MTX 15mg/week PO (+HCQ 400mg od) as per standard T2T practice. Follow-up (4, 12 and 24 weeks), dose escalation of MTX and treatment of flare will also be conducted in line with T2T care.
Patients with an abnormal T-cell frequency will be randomized 1:1 into 2 groups using randomly permuted block sizes and also followed up as per T2T care:
The first group (Arm B) will receive MTX 15mg/week PO (+HCQ 400mg od) The second group (Arm C) will receive MTX 15mg/week PO (+HCQ 400mg od) in combination with 50 mg subcutaneous Benepali® administered weekly.
Patients will be followed up for a period of 24 weeks and will undergo clinical, immunological and imaging assessments as stated in the study schedule. Following completion of the study, patients will either be followed up in our established inflammatory arthritis or biologics clinic. Patients in group C will discontinue their Benepali®.
This study will take place at the rheumatology out-patient department in Chapel Allerton Hospital, Leeds.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's planned enrollment of 106 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →University of Leeds is the lead sponsor of 200 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by:
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
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
Treatment Arm A will receive standard T2T care as per Arm B.
Drug: Sulfasalazine · Drug: Methotrexate · Drug: Hydroxychloroquine
Benepali will be adminstered subcutaneously at a dose of 50mg weekly and discontinued at the primary endpoint (24 weeks).
Also known as: Etanercept
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.
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.
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.
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
Time frame: 24 weeks
Clinical Remission at 12 weeks (Arms A vs B)
The difference in the proportions of patients in clinical remission (DAS28ESR ≤2.6) after 12 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies
Time frame: 12 weeks
Clinical Remission at 12 and 24 weeks (Arms B vs C)
The difference in the proportions of patients in clinical remission (DAS28ESR ≤2.6) at 12 weeks and 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
Time frame: 12 and 24 weeks
Sustained Clinical Remission
The difference in the proportions of patients achieving sustained clinical remission (DAS28ESR ≤2.6 at both 12 and 24 weeks) (Arm A vs. Arm B and Arm B vs. Arm C)
Time frame: 12 and 24 weeks
Patient Reported Outcomes at 12 and 24 weeks (Arm A vs B)
The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks \& 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) vs. abnormal (Arm B) naïve CD4+ T-cell frequencies
Time frame: 12 and 24 weeks
Patient Reported Outcomes at 12 and 24 weeks (Arm B vs C)
The differences in the medians of patient-reported outcome measures (EMS, VAS scales, HAQ-DI) after 12 weeks \& 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
Time frame: 12 and 24 weeks
Imaging Remission at 24 weeks (Arm A vs B)
The difference in the proportions of patients in imaging remission (Total power doppler synovitis score=0) after 24 weeks of first-line methotrexate with T2T care between those with normal (Arm A) or abnormal (Arm B) naïve CD4+ T-cell frequencies
Time frame: 24 weeks
Imaging Remission at 24 weeks (Arm B vs C)
The difference in the proportions of patients in imaging remission (Total power doppler synovitis score = 0) at 24 weeks for patients with abnormal baseline naïve CD4+ T-cell frequencies receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
Time frame: 24 weeks
Immunological Remission
The difference in the proportion of patients with normal naïve CD4+ T-cells at 24 weeks for patients with abnormal baseline naïve CD4+ T-cells receiving methotrexate with T2T care (Arm B) vs. etanercept + methotrexate (Arm C)
Time frame: 24 weeks
Cumulative Steroid Use
The difference in the average (median) cumulative amount of intramuscular corticosteroid use at 24 weeks between study arms (Arm A vs. Arm B and Arm B vs. Arm C). This will include any administered at the 24 week visit.
Time frame: 24 weeks
Plan to share: Undecided
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University of Leeds