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

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ClinicalTrials.gov Identifier: NCT03337165
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Alexander A Ostanin, Russian Academy of Medical Sciences

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.

Condition or disease Intervention/treatment Phase
Musculoskeletal Diseases Joint Disease Arthritis Arthritis, Rheumatoid Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Biological: tolerogenic dendritic cells Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
Actual Study Start Date : December 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: tolerogenic dendritic cells
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).
Biological: tolerogenic dendritic cells
dose-escalation




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337165


Contacts
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Contact: Alexey E Sizikov, PhD +7 (383) 228-59-45 depaidici@online.nsk.su
Contact: Yuliya D Kurochkina +7 (383) 228-59-45 juli_k@bk.ru

Locations
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Russian Federation
Institute of Fundamental and Clinical Immunology Recruiting
Novosibirsk, Russian Federation, 630099
Contact: Elena R Chernykh, MD, PhD    +7 (383) 236-03-29    ct_lab@mail.ru   
Contact: Alexander A Ostanin, MD, PhD    +7 (383) 236-03-29    ostanin62@mail.ru   
Sponsors and Collaborators
Russian Academy of Medical Sciences
Investigators
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Study Chair: Elena R Chernykh, MD, PhD Institute of Fundamental and Clinical Immunology
Principal Investigator: Alexander A Ostanin, MD, PhD Institute of Fundamental and Clinical Immunology

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Responsible Party: Alexander A Ostanin, Head of Clinical Department, Russian Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT03337165     History of Changes
Other Study ID Numbers: IFCI-14/10/2016
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Alexander A Ostanin, Russian Academy of Medical Sciences:
Rheumatoid arthritis
Auto-immune disorders
Tolerogenic Dendritic Cells

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Rheumatic Diseases
Joint Diseases
Collagen Diseases
Connective Tissue Diseases
Autoimmune Diseases
Musculoskeletal Diseases
Immune System Diseases