E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Determining the safety (occurrence of adverse events and disease flares) and tolerability of intranodal TolDCB29 administration. • Determining the feasibility of clinical grade TolDCB29 production from RA patient apheresis product
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E.2.2 | Secondary objectives of the trial |
• Demonstrating the qualitative and quantitative effects on HSP70/B29-specific T cells in response to TolDCB29 therapy • Evaluating the general characteristics of immune reactivity in response to TolDCB29 administration
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The first primary endpoint is the toxicity of the treatment at 20 weeks after the second TolDCB29 administration, defined as: • The occurrence of severe adverse events from administration of the first dose of TolDCB29 onwards • The occurrence of disease flares, defined as an increase in Disease Activity Score in 28 joints of >1.2 (or >0.6 if the former DAS28 was ≥ 3.2).
The second primary endpoint is the feasibility to generate sufficient numbers of TolDCB29 for the planned dose administrations to each participant |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
20 weeks after the second TolDCB29 administration |
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E.5.2 | Secondary end point(s) |
1. The induction and/or activation of HSP70/B29 specific T cells in response to TolDCB29 therapy 2. The general immune reactivity in response to TolDCB29 administration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4, 8, 12, and 24 weeks after the first TolDCB29 administration |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |