We aim to demonstrate the safety and feasibility of intranodal TolDCB29 administration. Our secondary objectives are the characterization of B29-peptide specific immune reactivity in response to TolDCB29 treatment and the evaluation of the effect of…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcomes are the occurrence of (serious) adverse events including
flares of disease activity in the four treatment groups, and the feasibility of
generating sufficient numbers of TolDCB29 from RA patient apheresis product.
Secondary outcome
Secondary outcomes are the qualitative and quantitative B29-specific T cell
response to treatment and the general immune reactivity to TolDCB29
administration. Our exploratory objective is the impact of the treatment on
clinical parameters.
Background summary
In rheumatoid arthritis, immune cells cause joint inflammation and destruction
in response to auto-antigens. Immunosuppressive therapies offer relief, but
fail to induce tolerance to auto-antigens. Injection of antigen-loaded
tolerogenic dendritic cells induces immune tolerance and ameliorates disease in
arthritis models. We hypothesize that dendritic cell therapy with TolDCB29 is
safe and induces immune tolerance in rheumatoid arthritis patients.
Study objective
We aim to demonstrate the safety and feasibility of intranodal TolDCB29
administration. Our 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.
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.
Study burden and risks
This study aims to demonstrate the safety of TolDCB29 therapy, and to
investigate whether the treatment affects rheumatoid arthritis disease
activity. Previous clinical trials with autologous DC in rheumatoid arthritis
and with HSP peptide and protein in diabetes and RA were proven safe in the
past. Serious risks for patients are therefore not expected. We anticipate that
the treatment with TolDCB29 may confer a clinical benefit by restoring immune
tolerance, which could allow for tapering of the current medication.
Patients included will undergo leukapheresis in Radboud UMC to harvest the
cells, and will receive the treatment in UMC Utrecht after preparation of cells
(within 3-6 weeks after leukapheresis). The TolDCB29 product will be
administered in two injections with a four week interval in between. After each
injection, vital functions will be monitored every 15 minutes during two hours.
From the first injection onwards, they will be followed for twenty-four weeks,
with detailed interviews, physical examination and laboratory testing every 4
weeks. Seventy mL of peripheral venous blood is collected at each of the five
hospital visits for immunomonitoring.
Heidelbergla 100
Utrecht 3584 CX
NL
Heidelbergla 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of rheumatoid arthritis according to the criteria which were valid
at time of diagnosis (i.e. 1987 Rheumatoid Arthritis Classification or 2010
ACR/EULAR RA Classification Criteria).
- Age 18 years or older
- Stable dose, for at least 12 weeks, of any combination of disease-modifying
anti-rheumatic 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, measured by disease activity
score of 28 joints < 3.2 for at least 12 weeks
- Able and willing to give informed consent and to comply with the study
protocol
Exclusion criteria
- Intramuscular or intra-articular glucocorticoid injection during 12 weeks
prior to inclu-sion
- 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)
- 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;
ALT/ALP>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. COPD, cardiac
failure
- Individuals of child bearing potential unwilling to use adequate
contraception for dura-tion of study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003620-20-NL |
| CCMO | NL71296.000.20 |