Clinical trial NCT03337165: Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
Official title: Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Musculoskeletal Diseases
Joint Disease
Arthritis
Arthritis, Rheumatoid
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Keywords: Rheumatoid arthritis
Auto-immune disorders
Tolerogenic Dendritic Cells
Lead sponsor: Russian Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.
timeFrame: within 6 months of injection
Secondary outcomes:
measure: Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable.
timeFrame: At final study visit, 6 months post treatment
measure: Change from Baseline in DAS28 Score.
timeFrame: Baseline, 1, 3 and 6 months post treatment
measure: Change from Baseline in the Health Assessment Questionnaire (HAQ)
timeFrame: Baseline, 1, 3 and 6 months post treatment
Other outcomes:
Locations:
city: Novosibirsk
country: Russian Federation
facility: Institute of Fundamental and Clinical Immunology
Study officials:
affiliation: Institute of Fundamental and Clinical Immunology
name: Elena R Chernykh, MD, PhD
role: STUDY_CHAIR
affiliation: Institute of Fundamental and Clinical Immunology
name: Alexander A Ostanin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: