Aldesleukin Therapy in Type 1 Diabetes

Conditions

Type 1 Diabetes MedDRA version: 20.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 20.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Marcovecchio ML, Wicker LS, Dunger DB, Dutton SJ, Kopijasz S, Scudder C, Todd JA, Johnson PRV.

2020-03-2017 citations

10.12688/wellcomeopenres.15697.1

Interventions

Trade Name: Proleukin Product Name: Aldesleukin Product Code: Aldesleukin Pharmaceutical Form: Solution for injection in pre-filled pen

Eligibility

Sex/Gender

All

Inclusion criteria

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 Are the trial subjects under 18? yes Number of subjects for this age range: 45 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Main Objective: To assess the effects of ultra-low dose aldesleukin on endogenous beta-cell function.; Secondary Objective: 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. ;Primary end point(s): Differences in slopes of DBS C-peptide over the 6 month-treatment period between the active and placebo groups.;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.	—

Measure

Time frame

Main Objective: To assess the effects of ultra-low dose aldesleukin on endogenous beta-cell function.; Secondary Objective: 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. ;Primary end point(s): Differences in slopes of DBS C-peptide over the 6 month-treatment period between the active and placebo groups.;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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Secondary

Measure	Time frame
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 ; 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	—

Measure

Time frame

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 ; 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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Countries

United Kingdom

Contacts

Public ContactCTRG

University of Oxford

ctrg@admin.ox.ac.uk00000000000

Outcome results

None listed