A single-site study to understand the best route of delivery for a new cell-based treatment created from patient's own white blood cells for rheumatoid arthritis
- Conditions
- Rheumatoid arthritisMusculoskeletal Diseases
- Registration Number
- ISRCTN14999554
- Lead Sponsor
- ewcastle upon Tyne Hospitals NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 20
1. Adults aged 18 years old or over
2. Rheumatoid Arthritis fulfilling 1987 ARA criteria or 2010 ACR/EULAR Classification Criteria
3. ACPA positive (>3x upper limit of normal)
4. Able and willing to give informed consent and comply with the study protocol
5. Disease duration at least 4 months and less than ten years
6. ACR Functional Class I-III
7. DAS 28 <5.1
8. If receiving disease-modifying anti-rheumatic drugs (DMARD) these can be at any dose or combination of methotrexate, sulphasalazine, azathioprine, hydroxychloroquine, abatacept, rituximab (last dose >6 months ago), TNF-alpha inhibitors and IL6 receptor antagonists but must have been stable for 4 weeks.
9. Stable dose of non-steroidal anti-inflammatory drugs (NSAID) for at least 4 weeks prior to screening (only applicable for patients taking NSAID as part of their standard care)
10. Possess at least one copy of a shared epitope HLA DRB1 allele (0101; 0102; 0105; 0401; 0404; 0405; 0408; 0409; 0410; 0413; 0416; 0419; 0421; 1001; 1402; 1406; 1409; 1413; 1417; 1419; 1420; 1421)
1. Use of other investigational medicinal products within 30 days prior to study entry (defined as date of consent into study)
2. Any Rheumatoid Arthritis treatment or dose changes within 4 weeks of study entry.
3. Current treatment with Janus kinase inhibitors or leflunomide. Previous treatment is permitted provided at least 12 weeks have elapsed since discontinuation of the therapy and study entry
4. Receiving glucocorticoids by any route within 4 weeks of study entry, apart from topical, intra-nasal or inhaled
5. Serious or unstable co-morbidity that prohibits participation in the study at the discretion of the investigator, eg. Significant COPD, significant cardiac failure, active malignancy
6. Active infection at study entry (except fungal nail infection)
7. Infection requiring hospitalisation, or IV antibiotics, within 4 weeks prior to study entry
8. Immunisation with live, attenuated vaccines planned within 14 days of baseline visit (administration of TolDCcitpep) and with non-live vaccines planned within 7 days of baseline visit
9. History of hepatitis B or C, HIV, or HTLV-1/2 infection(s)
10. Recent history of CMV infection (positive for CMV IgM antibodies) or syphilis infection (positive PCR test)
11. Major surgery within 8 weeks prior to study entry or planned within 12 weeks of baseline visit.
12. Pregnancy, or women planning to become pregnant within the study period, or women who are breast feeding
13. Females of child bearing potential engaging in heterosexual relationships unwilling to use adequate contraception for duration of study
14. Patients taking anticoagulants that cannot be interrupted and are, in the judgement of the investigator, likely to interfere with study procedures
15. Known hypersensitivity to local anaesthetic
16. Poor venous access or medical condition precluding leukapheresis e.g. unstable cardiac arrythmia (atrial fibrillation permitted)
17. Hb<10g/dL; neutrophils< 1.00 x10^9/L; platelets <100x10^9/
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Signs of immunomodulation will be measured from fresh blood, cryopreserved PBMC samples and lymph node aspirate samples. As there is currently no agreed biomarker for tolerance induction, we will use a range of modalities to identify levels of cell types and cell markers. Blood samples will be collected at baseline, 1, 3, and 6 weeks. Lymph node aspirate will be collected at baseline and 1 week.
- Secondary Outcome Measures
Name Time Method 1. Efficacy is measured using changes in American College of Rheumatology (ACR) criteria of a 20% improvement in the core set measures for a patient to reach improvement (ACR20), ACR50, ACR70 and Disease Activity Score (DAS-28) scores from baseline to weeks 1, 3, 6, and 12<br>2. Safety is measured using the reporting of adverse events and serious adverse events at baseline, 1, 3, 6, and 12 weeks<br>3. Patient acceptability is measured using a 1-5 Likert scale questionnaire at 12 weeks