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NCT Number: NCT03337165

Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis

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.

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Key information

Conditions

Musculoskeletal Diseases Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Disease Joint Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Institute of Fundamental and Clinical Immunology

Novosibirsk, 630099, Russia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

tolerogenic dendritic cells

Biological

dose-escalation

Primary outcomes

  1. Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.

    Time frame: 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 outcomes

  1. Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable.

    Time frame: 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.

  2. Change from Baseline in DAS28 Score.

    Time frame: 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.

  3. Change from Baseline in the Health Assessment Questionnaire (HAQ)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Russian Academy of Medical Sciences

Other

Registry information

Official study title

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

Acronym: TolDCfoRA

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Nov 8, 2017
Registry last updated
Sep 13, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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