- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01352858
Autologous Tolerogenic Dendritic Cells for Rheumatoid Arthritis (AutoDECRA) (AutoDECRA)
November 29, 2023 updated by: Newcastle University
Phase 1 Study of Autologous Tolerogenic Dendritic Cells for Rheumatoid Arthritis
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).
The investigators 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.
The investigators aim to treat 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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: John D Isaacs, PhD
- Phone Number: +441912225337
- Email: j.d.isaacs@ncl.ac.uk
Study Contact Backup
- Name: Jared Thornton, PhD
- Phone Number: +441912082597
- Email: Jared.Thornton@ncl.ac.uk
Study Locations
-
-
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Newcastle upon Tyne, United Kingdom, NE2 4HH
- Newcastle University
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Able and willing to give informed consent and to comply with the study protocol
- At least 6 month's disease duration
- ACR Functional Class I-III
- Age 18 years or over
- Active disease, including an inflamed (native) knee joint
- Failure (or intolerance of) at least one disease modifying anti-rheumatic drug (DMARD), including current therapy
- Morning stiffness in the target joint ≥ 30 minutes
- Willing and able to undergo arthroscopic procedures under local anaesthetic
- Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone≤10mg) for ≥4 weeks
- No intramuscular glucocorticoid administration for ≥ 6 weeks
- Stable dose of disease-modifying anti-rheumatic drug (DMARD) for ≥8 weeks
Exclusion Criteria:
- Use of other investigational medicinal products within 30 days prior to study entry (defined as date of recruitment into study)
- 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.
- Serious or unstable co-morbidity deemed unsuitable by PI, eg. COPD, cardiac failure
- History of malignancy (except treated basal cell carcinoma of skin)
- Known active infection at screening visit or at baseline (except fungal nail infection)
- Infection requiring hospitalization or IV antibiotics within 6 weeks of baseline
- Immunization with live vaccine within 6 weeks of baseline
- History of recurrent or chronic infection
- History of hepatitis B or C, syphilis, HIV or HTLV-1/2 infections
- Injection of target joint with glucocorticoids within 6 weeks of baseline
- Hb<10g/dL; neutrophils< 2.00 x109/L; platelets <150x109/L; ALT/ALP>2x upper limit of normal; elevated serum creatinine at screening visit.
- Major surgery within 8 weeks of baseline or planned within 3 months from baseline
- Pregnancy, or women planning to become pregnant within the study period, or women who are breast feeding
- Females or males of child bearing potential unwilling to use adequate contraception for duration of study
- Patients taking anticoagulants
- Known hypersensitivity to local or systemic corticosteroid therapy or local anaesthetic.
- Poor venous access or medical condition precluding leukapheresis
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TolDC
Experimental arm - TolDC administered arthroscopically
|
Tolerogenic dendritic cells (TolDC), derived ex vivo from autologous monocytes, administered arthroscopically into an inflamed knee following saline irrigation.
|
Placebo Comparator: Control
Arthroscopy & saline irrigation alone
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The proportion of patients experiencing AEs and SAEs following the intra-articular administration of TolDC.
Time Frame: within 3 months of injection
|
within 3 months of injection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
• The proportion of RA patients who enter the study, from whom GMP-grade TolDC of sufficient quality can be prepared (the success rate of the TolDC preparation procedure).
Time Frame: Within one week of donation of blood for extraction of TolDC
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Within one week of donation of blood for extraction of TolDC
|
|
• The proportion of patients who grade the trial and its related procedures as acceptable.
Time Frame: At final study visit, 3 months after study intervention.
|
Trial participants will assess acceptability of study specific procedures via an 'acceptability questionnaire' administered at the last study visit
|
At final study visit, 3 months after study intervention.
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Systemic RA disease activity
Time Frame: At baseline and at 7, 14 and 91 days post intervention
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Disease Activity Score using 28 joints (DAS28)
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At baseline and at 7, 14 and 91 days post intervention
|
Knee function
Time Frame: At baseline and at 7, 14 and 91 days post-intervention
|
Function will be assessed using the Health Assessment Questionnaire (HAQ), a standard instrument used in RA
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At baseline and at 7, 14 and 91 days post-intervention
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2012
Primary Completion (Actual)
November 1, 2018
Study Completion (Actual)
November 1, 2018
Study Registration Dates
First Submitted
May 11, 2011
First Submitted That Met QC Criteria
May 11, 2011
First Posted (Estimated)
May 12, 2011
Study Record Updates
Last Update Posted (Actual)
November 30, 2023
Last Update Submitted That Met QC Criteria
November 29, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AutoDECRA 1.0
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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