Musculoskeletal DiseasesPhase 1TolDCfoRANCT03337165
Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
A Phase 1 study testing tolerogenic dendritic cells in people with Musculoskeletal Diseases and Joint Disease, run by Russian Academy of Medical Sciences at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Musculoskeletal Diseases, Joint Disease, Arthritis
- What is being tested?
- tolerogenic dendritic cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteRussia
- Study dates
- Dec 2016to Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- Pregnancy
- Malignancy
- Participation in other clinical trials
Trial locations and contacts
1 site in 1 country.
Russia1 site
Institute of Fundamental and Clinical Immunology
Novosibirsk, 630099
About this study
Official title: Safety/Efficacy of Intra-articular Administration of 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.
Read the 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.
- Conditions
- Musculoskeletal Diseases, Joint Disease, Arthritis, Arthritis, Rheumatoid, Rheumatic Diseases, Connective Tissue Diseases
- Being tested
- tolerogenic dendritic cells
- Keywords
- Rheumatoid arthritis, Auto-immune disorders, Tolerogenic Dendritic Cells
- Medical subject headings
- Musculoskeletal Diseases, Joint Diseases, Arthritis, Arthritis, Rheumatoid, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tolerogenic dendritic cellsBiological
dose-escalation
| Study group | Role | What they receive |
|---|---|---|
| tolerogenic dendritic cells | Experimental | 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). Receives: Biological: tolerogenic dendritic cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within 6 months of injection
Secondary outcomes (3)
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.
Measured: At final study visit, 6 months post treatment
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.
Measured: Baseline, 1, 3 and 6 months post treatment
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.
Measured: Baseline, 1, 3 and 6 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study startDec 2016
- Primary completionMay 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Musculoskeletal DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Russian Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander A Ostanin, Russian Academy of Medical Sciences
- Investigators
- Elena R Chernykh, MD, PhD, Study chair, Institute of Fundamental and Clinical ImmunologyAlexander A Ostanin, MD, PhD, Principal investigator, Institute of Fundamental and Clinical Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337165
- Sponsor's protocol ID
- IFCI-14/10/2016
- Acronym
- TolDCfoRA
- Status last verified
- Sep 2019
- First submitted
- 3 Nov 2017
- Last updated
- 13 Sep 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety/Efficacy of Intra-articular Administration of Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03337165
- Acronym / sponsor ID
- TolDCfoRA / IFCI-14/10/2016
- Conditions
- Musculoskeletal Diseases, Joint Disease, Arthritis, Arthritis, Rheumatoid, Rheumatic Diseases, Connective Tissue Diseases
- Keywords
- Rheumatoid arthritis, Auto-immune disorders, Tolerogenic Dendritic Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Russian Academy of Medical SciencesUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 8 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tolerogenic dendritic cells | Experimental | Biological: tolerogenic dendritic cellsEach 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tolerogenic dendritic cellsdose-escalation | Biological | tolerogenic dendritic cells |
Primary outcome
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.
3 secondary outcomes
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
Change from Baseline in DAS28 Score.
Time frame: Baseline, 1, 3 and 6 months post treatment
Change from Baseline in the Health Assessment Questionnaire (HAQ)
Time frame: Baseline, 1, 3 and 6 months post treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena R Chernykh, MD, PhD study chair
Institute of Fundamental and Clinical Immunology
Alexander A Ostanin, MD, PhD principal investigator
Institute of Fundamental and Clinical Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tolerogenic dendritic cells in people with Musculoskeletal Diseases and Joint Disease, run by Russian Academy of Medical Sciences at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants experiencing AEs and SAEs following the intra-articular administration of tDCs. (time frame: within 6 months of injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2019.