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Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis (TolDCfoRA)

Primary Purpose

Musculoskeletal Diseases, Joint Disease, Arthritis

Status
Completed
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
tolerogenic dendritic cells
Sponsored by
Russian Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Musculoskeletal Diseases focused on measuring Rheumatoid arthritis, Auto-immune disorders, Tolerogenic Dendritic Cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Fundamental and Clinical Immunology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

tolerogenic dendritic cells

Arm Description

Each dose of autologous monocyte-derived dendritic cells generated in the presence of IFN-α/GM-CSF and tolerized with Dexamethasone (1x106, 3x106, 5x106, 8x106 and 10x106 cells in 2.0 mL sodium chloride 0.9% solution) will be administered in RA patients through intra-articular injection (into the knee joint).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
November 3, 2017
Last Updated
September 11, 2019
Sponsor
Russian Academy of Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03337165
Brief Title
Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
Acronym
TolDCfoRA
Official Title
Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
May 2019 (Actual)
Study Completion Date
August 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Russian Academy of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tolerogenic dendritic cells
Arm Type
Experimental
Arm Description
Each dose of autologous monocyte-derived dendritic cells generated in the presence of IFN-α/GM-CSF and tolerized with Dexamethasone (1x106, 3x106, 5x106, 8x106 and 10x106 cells in 2.0 mL sodium chloride 0.9% solution) will be administered in RA patients through intra-articular injection (into the knee joint).
Intervention Type
Biological
Intervention Name(s)
tolerogenic dendritic cells
Intervention Description
dose-escalation
Primary Outcome Measure Information:
Title
Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs.
Description
Occurrence and severity of adverse events following the intra-articular administration of tDCs will be evaluated within 6 months of injection.
Time Frame
within 6 months of injection
Secondary Outcome Measure Information:
Title
Number of Participants Who Rated the Study and its Components as Partly or Completely Acceptable.
Description
Participants will assess acceptability of study specific procedures via an "acceptability questionnaire" administered at the last study visit.
Time Frame
At final study visit, 6 months post treatment
Title
Change from Baseline in DAS28 Score.
Description
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.
Time Frame
Baseline, 1, 3 and 6 months post treatment
Title
Change from Baseline in the Health Assessment Questionnaire (HAQ)
Description
Functional status (disability) of participants will be assessed using the Health Assessment Questionnaire (HAQ), a standard instrument used in RA.
Time Frame
Baseline, 1, 3 and 6 months post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena R Chernykh, MD, PhD
Organizational Affiliation
Institute of Fundamental and Clinical Immunology
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Alexander A Ostanin, MD, PhD
Organizational Affiliation
Institute of Fundamental and Clinical Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Fundamental and Clinical Immunology
City
Novosibirsk
ZIP/Postal Code
630099
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis

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