Arthritis, Arthritis, Rheumatoid, Autoimmune Diseases, Connective Tissue Diseases, Immune System Diseases, Joint Disease, Musculoskeletal Diseases, Rheumatic Diseases
Conditions
Keywords
Rheumatoid arthritis, Auto-immune disorders, Tolerogenic Dendritic Cells
Brief summary
Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis and Crohn's disease. The general objective of this study is to evaluate the safety and tolerability of a single intra-articular injection (into the knee joint) of autologous monocyte-derived dendritic cells generated in the presence of interferon-alpha (IFN-α)/granulocyte-macrophage colony-stimulating factor (GM-CSF) and tolerized with Dexamethasone in rheumatoid arthritis (RA) patients.
Detailed description
A phase I dose-escalating clinical trial will be conducted to determine the safety and tolerability of a single intra-articular injection (into the knee joint) of autologous tolerogenic dendritic cells, and to enable selection of a suitable dose regimen for phase II trial. The primary objective of the phase I study will be to determine whether tDC-based therapy is safe and well tolerated and to establish the dose-response with disease activity measured over 6 months. Patients will serve as their own controls (pre- and post-treatment). Five doses of tDCs will be tested. The Study will start with intra-articular injection (into the knee joint) of 1x106 cells. Depending on safety/tolerability outcomes, the dose will gradually increase to 3x106, 5x106, 8x106 and 10x106 cells. The safety will be determined by the evaluation of the number of participants with adverse events (AEs) and severe adverse events (SAEs) following the intra-articular administration of tDC (within 6 months of injection). Systemic RA disease activity will be measured using DAS28 (Disease Activity Score using 28 joints) and the Health Assessment Questionnaire (HAQ), a standard instruments used in RA. Patients will be monitored at baseline and at 3, 7 days and 1, 3, 6 months post treatment.
Interventions
BIOLOGICALtolerogenic dendritic cells
dose-escalation
Sponsors
Russian Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 75 Years * Patients with moderate to severe active RA (DAS28 \>=3.2) * At least 6 month's disease duration * Synovitis of large joints (knee, elbow) * Morning stiffness in the target joint ≥ 30 minutes * Stable dose of disease-modifying anti-rheumatic drugs (DMARD) for ≥16 weeks * Patients must be able to tolerate all study procedures * Patients must be willing to voluntarily give written Informed Consent to participate in the study before any procedures are performed * Patients must be willing to be available for all baseline, treatment and follow-up examinations required by protocol
Exclusion criteria
* Injection of target joint with glucocorticoids within 6 weeks of baseline * Known hypersensitivity to gentamicin or local anaesthetics * Dementia, psychiatric disorders * Renal dysfunctions * Hemodynamic or respiratory instability * HIV or uncontrolled bacterial, fungal, or viral infections * Pregnancy * Malignancy * Participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs. | within 6 months of injection | Occurrence and severity of adverse events following the intra-articular administration of tDCs will be evaluated within 6 months of injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable. | At final study visit, 6 months post treatment | Participants will assess acceptability of study specific procedures via an acceptability questionnaire administered at the last study visit. |
| Change from Baseline in DAS28 Score. | Baseline, 1, 3 and 6 months post treatment | DAS28 calculated from the swollen joint count (SJC) and tender joint count (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour) and Patient Global Assessment of disease activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). A clinically meaningful improvement in DAS28 was defined as an improvement of 1.2 units. |
| Change from Baseline in the Health Assessment Questionnaire (HAQ) | Baseline, 1, 3 and 6 months post treatment | Functional status (disability) of participants will be assessed using the Health Assessment Questionnaire (HAQ), a standard instrument used in RA. |
Countries
Russia
Outcome results
None listed