Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis
| ISRCTN | ISRCTN87426082 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN87426082 |
| EudraCT/CTIS number | 2011-001582-41 |
| ClinicalTrials.gov number | NCT01352858 |
| Secondary identifying numbers | 12108 |
- Submission date
- 27/04/2012
- Registration date
- 27/04/2012
- Last edited
- 21/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof John Isaacs
Scientific
Scientific
Institute of Cellular Medicine
Claremont Road
Newcastle Upon Tyne
NE1 7RU
United Kingdom
| Phone | +44 191 208 5851 |
|---|---|
| john.isaacs@ncl.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Autologous TOlerogenic Dendritic Cells for Rheumatoid and Inflammatory Arthritis: a randomised controlled trial |
| Study acronym | AuTODeCRA |
| Study objectives | Current hypothesis as of 10/04/2014: This is a study which will look at safety, feasibility and acceptability of a new therapy called tolerogenic dendritic cells (TolDC), derived from the patient's own white blood cells, which will be injected into the knee joints of rheumatoid and inflammatory arthritis patients, using a procedure called arthroscopy (a camera examination of a joint). We are also looking to see if the drug has any effect on the disease activity (if it can help in IA) and whether the drug can affect the immune system. Previous hypothesis: This is a study which will look at safety, feasibility and acceptability of a new therapy called tolerogenic dendritic cells (TolDC), derived from the patient's own white blood cells, which will be injected into the knee joints of rheumatoid arthritis patients, using a procedure called arthroscopy (a camera examination of a joint). We are also looking to see if the drug has any effect on the disease activity (if it can help in RA) and whether the drug can affect the immune system. More details can be found at http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=12108 On 10/04/2014 the following changes were made to the trial record: 1. The public title was changed from 'AUTOlogous TOlerogenic DEndritic Cells for Rheumatoid Arthritis' to 'Autologous TOlerogenic Dendritic Cells for Rheumatoid and Inflammatory Arthritis ' 2. The scientific title was changed from 'AUTOlogous TOlerogenic DEndritic Cells for Rheumatoid Arthritis: a randomised controlled trial' to 'Autologous TOlerogenic Dendritic Cells for Rheumatoid and Inflammatory Arthritis: a randomised controlled trial' 3. The acronym was changed from 'AUTODECRA' to 'AuTODeCRA' 4. The anticipated end date was changed from 24/02/2013 to 31/08/2014 |
| Ethics approval(s) | NRES committee North East Sunderland, 20/01/2012, ref: 11/NE/0140 |
| Health condition(s) or problem(s) studied | Topic: Musculoskeletal; Subtopic: Musculoskeletal (all Subtopics); Disease: Inflammatory Arthritis |
| Intervention | Tolerogenic Dendritic Cells, Autologous Tolerogenic Dendritic Cells; Study Entry : Single Randomisation only 12 patients in total, 9 with TolDC and 3 with a control treatment. Three doses of TolDC will be tested, 3 patients per dose. Subjects will have RA and at least one swollen knee joint. They will undergo a knee ultrasound scan, fill in a series of questionnaires, have their knee aspirated (fluid taken out) and finally undergo a procedure called leukapheresis (removal of white blood cells) from which the treatment will be manufactured. Subsequently they will undergo 3 arthroscopies (camera examination of the knee joint) over a period of about 12 weeks. On the first arthroscopy they will have the TolDC injected into their knee joint. They will then spend the night at the Clinical Research facility for observation. Over the next 5 days they will be telephoned daily by the study doctor to check how they are, and will be reassessed if needed. About 2 weeks later they will have their second arthroscopy to look for effects of treatment, and the third will take place at 13 weeks (end of study) or sooner if the knee appears to get worse. |
| Intervention type | Other |
| Primary outcome measure | Proportion of patients experiencing adverse events (AEs) and serious adverse events (SAEs) following administration of TolDC; Timepoint(s): 3 months |
| Secondary outcome measures | Added 10/04/2014: 1. The proportion of IA patients who enter the study, from whom GMP-grade TolDC of sufficient quality can be prepared (the success rate of the TolDC preparation procedure) 2. The proportion of patients who grade the trial and its related procedures as acceptable (trial participants will assess acceptability of study-specific procedures via an acceptability questionnaire administered at the last study visit) |
| Overall study start date | 24/02/2012 |
| Completion date | 31/08/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 12; UK Sample Size: 12 |
| Key inclusion criteria | Current inclusion criteria as of 10/04/2014: 1. Participants will be patients with rheumatoid arthritis according to the 1987 or 2010 American College of Rheumatology (ACR) classification criteria or inflammatory arthritis 2. Able and willing to give informed consent and to comply with the study protocol 3. At least 6 months duration 4. ACR Functional Class I-III (for RA patients) 5. Age 18 years or over 6. Active disease, including an inflamed (native) knee joint 7. Failure (or intolerance of) at least one disease modifying anti-rheumatic drug (DMARD), including current therapy 8. Morning stiffness in the target joint greater than or equal to 30 minutes 9. Willing and able to undergo arthroscopic procedures under local anaesthetic 10. Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone10mg) for >/=4 weeks 11. No intramuscular glucocorticoid administration for 6 weeks 12. Stable dose of disease-modifying anti-rheumatic drug (DMARD) for >/= 8 weeks 13. Target Gender: Male & Female Previous inclusion criteria: 1. Participants will be patients with rheumatoid arthritis according to the 1987 or 2010 American College of Rheumatology (ACR) classification criteria 2. Able and willing to give informed consent and to comply with the study protocol 3. At least 6 months duration 4. ACR Functional Class I-III 5. Age 18 years or over 6. Active disease, including an inflamed (native) knee joint 7. Failure (or intolerance of) at least one disease modifying anti-rheumatic drug (DMARD), including current therapy 8. Morning stiffness in the target joint 30 minutes 9. Willing and able to undergo arthroscopic procedures under local anaesthetic 10. Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone¡10mg) for >/=4 weeks 11. No intramuscular glucocorticoid administration for 6 weeks 12. Stable dose of disease-modifying anti-rheumatic drug (DMARD) for >/= 8 weeks weeks 13. Target Gender: Male & Female |
| Key exclusion criteria | 1. Use of other investigational medicinal products within 30 days prior to study entry (defined as date of recruitment into study) 2. Patients who have received rituximab therapy and whose B-cell count remains below the normal range. Patients who have received any other cell depleting therapies and whose cell counts have not returned to the normal range, at the discretion of the principal investigator (PI). 3. Serious or unstable co-morbidity deemed unsuitable by PI, eg. Chronic obstructive pulmonary disease (COPD), cardiac failure 4. History of malignancy (except treated basal cell carcinoma of skin) 5. Known active infection at screening visit or at baseline (except fungal nail infection) 6. Infection requiring hospitalization or IV antibiotics within 6 weeks of baseline 7. Immunization with live vaccine within 6 weeks of baseline 8. History of recurrent or chronic infection 9. History of hepatitis B or C, syphilis, Human immunodeficiency virus (HIV) or Human T-lymphotropic virus (HTLV1/2) infections 10. Injection of target joint with glucocorticoids within 6 weeks of baseline 11. Hb<10g/dL; neutrophils< 2.00 x109/L; platelets <150x109/L; Alanine transaminase/Alkaline phosphatase (ALT/ALP)>2x upper limit of normal; elevated serum creatinine at screening visit 12. Major surgery within 8 weeks of baseline or planned within 3 months from baseline 13. Pregnancy, or women planning to become pregnant within the study period, or women who are breast feeding 14. Females or males of child bearing potential unwilling to use adequate contraception for duration of study 15. Patients taking anticoagulants 16. Hypersensitivity to local or systemic corticosteroid therapy or local anaesthetic 17. Poor venous access or medical condition precluding leukapheresis |
| Date of first enrolment | 24/02/2012 |
| Date of final enrolment | 31/08/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Institute of Cellular Medicine
Newcastle Upon Tyne
NE1 7RU
United Kingdom
NE1 7RU
United Kingdom
Sponsor information
Newcastle Hospitals Foundation NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Wolfson Unit of Clinical Pharmacology, Institute of Cellular Medicine
Framlington Place
Newcastle Upon Tyne
NE2 4HH
England
United Kingdom
"ROR" |
https://ror.org/05p40t847 |
|---|
Funders
Funder type
Charity
Arthritis Research UK (UK)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/01/2017 | 21/01/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
21/01/2019: Publication reference added
07/03/2017: No publications found in PubMed, verifying study status with principal investigator
