NCT05251870

Tolerogenic Dendritic Cell Therapy for Rheumatoid Arthritis

Tolerogenic Dendritic Cell Therapy for Rheumatoid Arthritis: the TOLERANT Trial

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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. 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.

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	autologous mature tolerogenic monocyte-derived Dendritic Cells loaded with the B29 peptide of HSP70	Intranodal administration into an inguinal lymphnode. Two administrations at the same injection site with a four week interval.

Timeline

• Start date: 2021-08-17
• Primary completion: 2024-08-01
• Completion: 2025-08-01
• First posted: 2022-02-23
• Last updated: 2022-02-23

Locations

3 sites across 1 country: Netherlands