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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To assess the effects of ultra-low dose aldesleukin on endogenous beta-cell function. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives 1)To assess the efficacy of regular dosing of aldesleukin in increasing Treg levels 2)To confrm the clinical safety and tolerability of ultra-low dose aldesleukin 3) To assess changes in the immune system indicating benefit or potential risk for future gains/loss in beta-cell function and immune function. 4) To assess treatment effect on glycaemic control 5) To assess treatment effect on the immune activity and inflammatory marker CRP, as measured by frequent home dried blood spots.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have given written informed consent to participate or assent with parental consent 2. Be aged 6-18 years 3. Be diagnosed with T1D (at least one autoantibody positive), requiring insulin treatment 4. Be within 6 weeks from diagnosis of T1D 5. Have a random C-peptide > 200 pmol/l 6. Normal full blood count
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E.4 | Principal exclusion criteria |
1. Non-type 1 diabetes (type 2 or monogenic diabetes) and secondary diabetes 2. Uncontrolled thyroid and coeliac diseases 3. Hypersensitivity to aldesleukin or any of the excipients 4. History of severe cardiac disease (NYHA Class III or IV) a. See Appendix D 5. History of malignancy within the past 5 years (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ) 6. Participation in another clinical trial (CTIMP) within 4 months prior to screening 7. Females who are pregnant, lactating or intend to get pregnant during the study 8. Females of childbearing potential who are unwilling or unable to comply with contraceptive advice and regular pregnancy testing throughout the trial 9. Current use of immunosuppressive agents or steroids 10. Active clinical infections – participants can be recruited after a minimum period of 48 h after last day of feeling unwell or last day of antibiotic/anti-viral treatment 11. Immunisations – participants can be recruited after a minimum of 14 days following immunisation. Routine vaccinations should be avoided for the 6-month duration of treatment and for 30 days afterwards 12. Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the participant ineligible for inclusion because of a safety concern 13. Children with compliance problems
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E.5 End points |
E.5.1 | Primary end point(s) |
Differences in slopes of DBS C-peptide over the 6 month-treatment period between the active and placebo groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DBS for c-peptide taken weekly through the treatment phase (6 months) and then monthly during the follow-up period. |
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E.5.2 | Secondary end point(s) |
1) Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline 2) Safety will be assessed at each visit by: Physical examination, including assessment of the most commonly reported reactions to low- or high-dose aldesleukin, namely influenza-like syndrome, skin reaction, diarrhea, nausea; vital signs (temperature, weight, blood pressure, heart rate); abnormal laboratory parameters (liver, kidney function, full blood count); reporting of adverse events. 3) Changes in the absolute numbers of T, B and NK cells. A whole blood 6-color BD TBNK Multitest™ assay using BD Trucount Tubes according to the manufacturers’ instructions (BD Biosciences) will be run to determine the relative and absolute concentration of lymphocyte subpopulations, including mature T, B and NK cells. 4) Change in HbA1c and daily insulin requirements during the trial period. 5) Change in CRP levels during the trial period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment 2) At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment 3) At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment 4) HbA1c: At baseline and then 3,6 and 12 months Insulin dose data: Baseline and then 1, 2, 3, 6 and 12 months 5) Weekly DBS CRP collected during the 6-month treatment period, and monthly during the 6 months post-treatment period
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 5 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 30 |