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Rheumatoid ArthritisPhase 1/2TOLERANTNCT05251870

Tolerogenic Dendritic Cell Therapy for Rheumatoid Arthritis

A Phase 1/2 study testing autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 in people with Rheumatoid Arthritis, run by UMC Utrecht at 3 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Rationale: In rheumatoid arthritis, immune cells cause joint inflammation and destruction in response to autoantigens. Immunosuppressive therapies offer relief but fail to induce tolerance to autoantigens. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesNetherlands
Study dates
17 Aug 2021to Aug 2025
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of rheumatoid arthritis (RA) according to the criteria which were valid at time of diagnosis (i.e. 1987 Rheumatoid Arthritis Classification or 2010 American College of Rheumatology/EULAR RA Classification Criteria)
  • Stable dose, for at least 12 weeks, of any combination of disease-modifying antirheumatic drugs and glucocorticoids (maximum of 7.5 mg per day), with exception of those drugs that are part of the exclusion criteria.
  • Disease in remission or in low disease activity for at least 12 weeks (disease activity score of 28 joints < 3.2)
  • Able and willing to give informed consent and to comply with the study protocol

Who cannot join

  • Intramuscular or intra-articular glucocorticoid injection during 12 weeks prior to inclusion
  • Use of JAK inhibitors
  • Active or chronic infection (except fungal nail infection)
  • Infection requiring hospitalization or IV antibiotics within 6 weeks of baseline
  • Immunization with live vaccine within 6 weeks of baseline
  • History of malignancy (except treated basal cell carcinoma of skin)
Show all 13Show fewer
  • Use of other investigational medicinal products within 30 days prior to study entry
  • Major surgery within 8 weeks of baseline or planned within 12 weeks from baseline
  • Pregnancy, or women planning to become pregnant within the study period, or women who are breast feeding
  • Hb<6 mmol/L; neutrophils< 2.00 x10^9/L; platelets <150x10^9/L; alanine aminotransferase or alkaline phosphatase>2x upper limit of normal; renal insufficiency (clearance < 60 ml/min) at screening visit
  • Poor venous access or medical condition precluding leukapheresis
  • Serious or unstable co-morbidity deemed unsuitable by PI, e.g. chronic obstructive pulmonary disease, cardiac failure
  • Individuals of child bearing potential unwilling to use adequate contraception for duration the of study

Trial locations and contacts

3 sites in 1 country.

Arie J Stoppelenburg, PhD contact

+31302535589

a.j.stoppelenburg@umcutrecht.nl

Research nurses contact

tolerant@umcutrecht.nl

Netherlands3 sites, 1 recruiting

  • Radboud University Medical Centre

    Nijmegen

    Active, not recruiting

  • University Medical Centre Utrecht

    Utrecht

    Recruiting

  • Utrecht University

    Utrecht

    Active, not recruiting

Other trials in Netherlands

About this study

Official title: Tolerogenic Dendritic Cell Therapy for Rheumatoid Arthritis: the TOLERANT Trial

Rationale: In rheumatoid arthritis, immune cells cause joint inflammation and destruction in response to autoantigens. Immunosuppressive therapies offer relief but fail to induce tolerance to autoantigens. Injection of antigen-loaded tolerogenic dendritic cells induces immune tolerance and ameliorates disease in arthritis models. The investigators hypothesize that dendritic cell therapy with TolDCB29 is safe and induces immune tolerance in rheumatoid arthritis patients.

Objective: The aim of the study is to demonstrate the safety and feasibility of intranodal TolDCB29 administration. Secondary objectives are the characterization of B29-peptide specific immune reactivity in response to TolDCB29 treatment and the evaluation of the effect of the treatment on disease activity.

Read more

Study design: Phase I/II, open-label, dose-escalation clinical trial. Study population: Adult patients (>18 years) with rheumatoid arthritis in remission or low disease activity while on disease modifying anti-rheumatic drugs (DMARD) will be included. Any combination and dose of DMARD is allowed, with exception of Janus kinase inhibitors. Concomitant use of a low dose of prednisone (7.5 mg per day or below) is allowed. Medication should be stable for at least twelve weeks. 18 patients will undergo the experimental treatment.

Intervention: Study participants will receive two intranodal injections with the TolDCB29 product with a four-week interval. During the first phase of the study dose escalation is performed, in which the first group (n=3) receives two "low dose" injections, the second group (n=3) receives two "intermediate dose" injections, and the third group (n=3) receives two "high dose" injections. During the second phase, a fourth group (n=9) will receive the highest dosage without attributable serious adverse events thus far.

Being tested
autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Keywords
Tolerogenic Dendritic Cells
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70Drug

    Also called TolDCB29

    Intranodal administration into an inguinal lymphnode. Two administrations at the same injection site with a four week interval.

Study groups in NCT05251870
Study groupRoleWhat they receive
Intranodal TolDCB29 (low dose)ExperimentalTwo administrations of 5 million autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 (TolDCB29). This cohort will consist of three patients.
Receives: Drug: autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Intranodal TolDCB29 (intermediate dose)ExperimentalTwo administrations of 10 million autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 (TolDCB29). This cohort will consist of three patients.
Receives: Drug: autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Intranodal TolDCB29 (high dose)ExperimentalTwo administrations of 15 million autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 (TolDCB29). This cohort will consist of three patients.
Receives: Drug: autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70
Intranodal TolDCB29 (recommended dose)ExperimentalTwo administrations of the recommended dose of autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 (TolDCB29). The recommended dose will be advised by the data safety monitoring board after data review of the first three arms. This cohort will consist of nine patients.
Receives: Drug: autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety as assessed by the occurrence and severity of adverse events

    The occurrence and severity of adverse events will be recorded, including the occurrence of disease flares.

    Measured: 34 weeks

  2. Quantity of good manufacturing practices (GMP)-grade TolDCB29 released according to Quality Control.

    Number of TolDCB29 cells (millions of cells) per patient that were released according to the quality control standards of the IMPD.

    Measured: 34 weeks

  3. Occurrence of out of specification (OOS) products.

    Number of occurrences that out of specification TolDCB29 products were generated during manufacturing and/or reconsitution.

    Measured: 34 weeks

Secondary outcomes (3)

  1. Changes in leukocyte numbers

    Measured: 34 weeks

  2. Changes in CD4+ T lymphocytes subset frequencies

    Measured: 34 weeks

  3. Lymphocyte proliferation to HSP70/B29 peptide

    Measured: 34 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2022
  2. Study start17 Aug 2021
  3. Primary completionAug 2024 (estimated)
  4. Study completionAug 2025 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05251870
Sponsor's protocol ID
NL71296.000.20
Other IDs
2019-003620-20, 2019
Acronym
TOLERANT
Status last verified
Feb 2022
First submitted
21 Dec 2021
Last updated
23 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Stoppelenburg AJ, Schreibelt G, Koeneman B, Welsing P, Breman EJ, Lammers L, de Goede A, Duiveman-de Boer T, van Eden W, Leufkens P, de Vries IJM, Broere F, van Laar JM. Design of TOLERANT: phase I/II safety assessment of intranodal administration of HSP70/mB29a self-peptide antigen-loaded autologous tolerogenic dendritic cells in patients with rheumatoid arthritis. BMJ Open. 2024 Sep 12;14(9):e078231. doi: 10.1136/bmjopen-2023-078231.

    PubMed 39266308

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70 in people with Rheumatoid Arthritis, run by UMC Utrecht at 3 sites in Netherlands.

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 4 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 23 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Arie J Stoppelenburg, PhD (+31302535589, a.j.stoppelenburg@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as assessed by the occurrence and severity of adverse events (time frame: 34 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05251870, which also lists 1 linked publication.

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 23 Feb 2022.

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