Targeting the rheumatoid arthritis synovial fibroblast via cyclin dependent kinase inhibition - an early phase trial
- Conditions
- Rheumatoid arthritisMusculoskeletal DiseasesRheumatoid arthritis, unspecified
- Registration Number
- ISRCTN36667085
- Lead Sponsor
- ewcastle Hospitals Foundation NHS Trust (UK)
- Brief Summary
2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32590730/ protocol (added 29/06/2020) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33928262/ (added 05/05/2021)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 15
Current inclusion criteria as of 11/08/2017:
1. Rheumatoid arthritis fulfilling the 1987 ACR or 2010 ACR/EULAR criteria
2. Age 18 years and over
3. At least 6 months’ disease duration
4. ACR Functional Class I-III
5. DAS28 =3.2 (for Part 1 only)
6. DAS28 =4.0, with clinical synovitis in at least three joints, at least one of which is a joint amenable to ultrasound-guided synovial biopsy (knee, elbow, ankle, wrist, MCP or PIP joint) (for part 2 only)
7. Currently taking anti-TNF as part of standard clinical care, and have received anti-TNF therapy for at least 3 months upon entry to the study
8. Anti-TNF may be administered as either monotherapy or with background conventional DMARDs. Permitted background DMARDs are methotrexate, sulphasalazine and hydroxychloroquine, either alone or in combination, at stable dose(s) for =4 weeks prior to baseline visit
9. Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone=7.5mg) for =4 weeks
10. No intramuscular glucocorticoid administration in the 4 week period prior to baseline visit
11. Willing and able to undergo MRI scanning on two occasions. (For Part 2 only)
12. Willing to undergo ultrasound guided synovial biopsy on two occasions (under local anaesthetic). (For part 2 only)
Previous inclusion criteria:
1. Rheumatoid arthritis fulfilling the 1987 ACR or 2010 ACR/EULAR criteria
2. Age 18 years or above
3. At least 6 months? disease duration
4. ACR Functional Class IIII
5. DAS28 =4.0, with clinical synovitis in at least three joints, at least one of which is a joint amenable to ultrasound-guided synovial biopsy (knee, elbow, ankle, wrist, MCP or PIP joint). (For part 2 only).
6. Currently taking anti-TNF monotherapy as part of standard clinical care and have received anti-TNF therapy for at least 6 months upon entry to the study as per NICE guidelines.
7. Willing to undergo ultrasound guided synovial biopsy on two occasions (under local anaesthetic). (For part 2 only).
8. Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone=7.5mg) for =4 weeks.
9. No intramuscular glucocorticoid administration in the 6 week period prior to baseline visit.
10. Willing and able to undergo MRI scanning on two occasions (Part 2 only).
Current exclusion criteria as of 11/08/2017:
1. If patients were previously taking leflunomide a minimum period of 20 days must have elapsed between the last dose of leflunomide and the first dose of IMP
2. Patients receiving warfarin or other anticoagulation likely to interfere with biopsy procedures (part 2 only)
3. Use of other investigational medicinal products within 30 days prior to trial entry (defined as date of recruitment into trial)
4. Serious or unstable co-morbidity deemed unsuitable by PI e.g. COPD, cardiac failure, other significant autoimmune disease
5. Patients must not drink more than 2 units of alcohol per day and no more than 10 units of alcohol per week during the trial and for a 4 week period after completion of the trial
6. Known active infection at screening visit or at baseline (except fungal nail infection)
7. Infection requiring hospitalization or IV antibiotics within 6 weeks prior to baseline
8. History of recurrent or chronic infection
9. Recent live vaccination (within 6 weeks of baseline)
10. Hb<10g/dL; neutrophils< 1.5 x109/L; platelets <100x109/L
11. Patients taking ketoconazole, voriconazole, erythromycin, clarithromycin.
12. ALT/AST/ALP>1.5x upper limit of normal
13. Glomerular filtration rate < 60ml/minute (Cockroft formula)
14. Major surgery within 8 weeks prior to baseline or planned within 3 months from baseline
15. Pregnancy, or women planning to become pregnant within the trial period, or women who are breastfeeding
16. Females or males of child bearing potential unwilling to use two forms of adequate contraception whilst taking the IMP and for one month afterwards
Previous exclusion criteria:
1. Patients currently taking, and planning to continue, methotrexate, other non-biologic DMARDs or biologic therapies other than anti-TNF therapy. For patients recently receiving non-biologic DMARD therapy at least 8 weeks must have elapsed following discontinuation of treatment prior to enrolment into the current study. If patients were previously taking leflunomide this must have been washed out with cholestyramine or activated charcoal according to leflunomide?s Summary of Product Characteristics
2. Patients receiving warfarin or other anticoagulation likely to interfere with biopsy procedures (part 2 only)
3. Previous participation in this trial (for Part 2 participants)
4. Use of other investigational medicinal products within 30 days prior to trial entry (defined as date of recruitment into trial)
5. Serious or unstable co-morbidity deemed unsuitable by PI e.g. COPD, cardiac failure, other significant auto-immune disease
6. Patient?s must not drink more than 2 units of alcohol per day and no more than 10 units of alcohol per week during the trial and for a 4 week period after completion of the trial
7. Known active infection at screening visit or at baseline (except fungal nail infection)
8. Infection requiring hospitalization or IV antibiotics within 6 weeks prior to baseline
9. History of recurrent or chronic infection
10. Recent live vaccination (within 6
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method