Rheumatoid Arthritis
Conditions
Keywords
Tolerogenic Dendritic Cells
Brief summary
Rationale: In rheumatoid arthritis, immune cells cause joint inflammation and destruction in response to autoantigens. Immunosuppressive therapies offer relief but fail to induce tolerance to autoantigens. Injection of antigen-loaded tolerogenic dendritic cells induces immune tolerance and ameliorates disease in arthritis models. The investigators hypothesize that dendritic cell therapy with TolDCB29 is safe and induces immune tolerance in rheumatoid arthritis patients. Objective: The aim of the study is to demonstrate the safety and feasibility of intranodal TolDCB29 administration. Secondary objectives are the characterization of B29-peptide specific immune reactivity in response to TolDCB29 treatment and the evaluation of the effect of the treatment on disease activity. Study design: Phase I/II, open-label, dose-escalation clinical trial. Study population: Adult patients (\>18 years) with rheumatoid arthritis in remission or low disease activity while on disease modifying anti-rheumatic drugs (DMARD) will be included. Any combination and dose of DMARD is allowed, with exception of Janus kinase inhibitors. Concomitant use of a low dose of prednisone (7.5 mg per day or below) is allowed. Medication should be stable for at least twelve weeks. 18 patients will undergo the experimental treatment. Intervention: Study participants will receive two intranodal injections with the TolDCB29 product with a four-week interval. During the first phase of the study dose escalation is performed, in which the first group (n=3) receives two low dose injections, the second group (n=3) receives two intermediate dose injections, and the third group (n=3) receives two high dose injections. During the second phase, a fourth group (n=9) will receive the highest dosage without attributable serious adverse events thus far.
Interventions
DRUGautologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Intranodal administration into an inguinal lymphnode. Two administrations at the same injection site with a four week interval.
Sponsors
Radboud University Medical Center
Utrecht University
Trajectum Pharma B.V.
Dutch Arthritis Association
ZonMw: The Netherlands Organisation for Health Research and Development
Health Holland
UMC Utrecht
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of rheumatoid arthritis (RA) according to the criteria which were valid at time of diagnosis (i.e. 1987 Rheumatoid Arthritis Classification or 2010 American College of Rheumatology/EULAR RA Classification Criteria) * Stable dose, for at least 12 weeks, of any combination of disease-modifying antirheumatic drugs and glucocorticoids (maximum of 7.5 mg per day), with exception of those drugs that are part of the
Exclusion criteria
. * Disease in remission or in low disease activity for at least 12 weeks (disease activity score of 28 joints \< 3.2) * Able and willing to give informed consent and to comply with the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of good manufacturing practices (GMP)-grade TolDCB29 released according to Quality Control. | 34 weeks | Number of TolDCB29 cells (millions of cells) per patient that were released according to the quality control standards of the IMPD. |
| Occurrence of out of specification (OOS) products. | 34 weeks | Number of occurrences that out of specification TolDCB29 products were generated during manufacturing and/or reconsitution. |
| Safety as assessed by the occurrence and severity of adverse events | 34 weeks | The occurrence and severity of adverse events will be recorded, including the occurrence of disease flares. |
Secondary
| Measure | Time frame |
|---|---|
| Changes in CD4+ T lymphocytes subset frequencies | 34 weeks |
| Changes in leukocyte numbers | 34 weeks |
| Lymphocyte proliferation to HSP70/B29 peptide | 34 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life (EQ-5D-5L) | 34 weeks | Score ranges from less than 0 to 1. In this score, 0 represents a health state equivalent to death and 1 represents full health. |
| Autoantibody levels | 34 weeks | Blood autoantibody levels in Units/mL |
| Mean functional ability (HAQ) | 34 weeks | Score ranges 0 - 3.0 in 0.1 increments. Higher scores indicate worse function and greater disability. |
| Disease activity of 28 joints (DAS28) | 34 weeks | Score ranges 0 - 9.4. Higher score means higher disease activity |
Countries
Netherlands
Contacts
Primary ContactArie J Stoppelenburg, PhD
Backup ContactResearch nurses
Outcome results
None listed