Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

— TolDCfoRA  

Official title:

Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03337165
• Other study ID #: IFCI-14/10/2016
• Status: Completed
• Phase: Phase 1
• Start date: December 2016
• Est. completion date: August 2019

Study information

• Verified date: September 2019
• Source: Russian Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Autoimmune Diseases
• Collagen Diseases
• Connective Tissue Diseases
• Immune System Diseases
• Joint Disease
• Joint Diseases
• Musculoskeletal Diseases
• Rheumatic Diseases

Intervention

Biological:
• tolerogenic dendritic cells
dose-escalation

Locations

Country	Name	City	State
Russian Federation	Institute of Fundamental and Clinical Immunology	Novosibirsk

Sponsors (1)

Lead Sponsor	Collaborator
Russian Academy of Medical Sciences

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.	Occurrence and severity of adverse events following the intra-articular administration of tDCs will be evaluated within 6 months of injection.	within 6 months of injection
Secondary	Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable.	Participants will assess acceptability of study specific procedures via an "acceptability questionnaire" administered at the last study visit.	At final study visit, 6 months post treatment
Secondary	Change from Baseline in DAS28 Score.	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.	Baseline, 1, 3 and 6 months post treatment
Secondary	Change from Baseline in the Health Assessment Questionnaire (HAQ)	Functional status (disability) of participants will be assessed using the Health Assessment Questionnaire (HAQ), a standard instrument used in RA.	Baseline, 1, 3 and 6 months post treatment