Phase 1b study of proinsulin (PI) peptide immunotherapy in new onset type 1 diabetes

INTERVENTION: 1. Study drug will be administered intradermally at a frequency of either bi‐weekly or 4 times a week 2. To maintain blinding, all subjects will receive injections at bi‐weekly intervals 3. In the case of the placebo group this will be normal saline only 4. For the Low Frequency dosing group this will be alternate study drug and normal saline only 5. For the High Frequency dosing group this will be study drug on every occasion 6. Injections will be administered over 22 weeks to achieve a total of 12 7. Thus the cumulative dose in the Low Frequency group will be 60ìg and in the High Frequency group 120 ìg CONDITION: Newly diagnosed type 1 diabetes ; Nutritional, Metabolic, Endocrine ; Insulin‐dependent diabetes mellitus PRIMARY OUTCOME: Assessment of the safety of PPI C19‐A3 peptide administration in subjects with new‐onset Type 1 diabetes SECONDARY OUTCOME: 1. Change in stimulated C‐peptide production at 12, 24, 36 and 48 weeks versus baseline and between groups; 2. Change in level or quality of T lymphocyte biomarkers of alpha cell specific immune response at 12, 24, 36 and 48 weeks versus baseline and between groups; 3. Change in level or quality of islet cell autoantibody biomarkers of alpha‐cell specific immune response at 12, 24, 36 and 48 weeks versus baseline and between groups; 4. Change in glycated haemoglobin (as measured by % HbA1c levels), daily insulin usage, and mean amplitude of glucose excursions at 12, 24, 36 and 48 weeks versus baseline and between groups; 5. Changes in the Hypoglycaemia Fear Survey (HFS), and Diabetes Treatment Satisfaction Questionnaire (DTSQs) scores at 3,6 and 12 months and ADDQoL (Audit of Diabetes‐Dependent Quality of Life) at 6, and 12 months versus baseline and between groups; 6. The DTSQc (Diabetes Treatment Satisfaction Questionnaire, change version) will also be compared between groups at 12 months INCLUSION CRITERIA: 1. Age 18‐40 years 2. Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection) 3. Possession of HLA‐DRB1*04:01 allele 4. At least one positive islet cell autoantibody (ie anti‐GAD65, antibodies to insulinoma‐associated antigen‐2 (IA‐2) or zinc transporter 8 (ZnT8)). 5. Peak insulin C‐peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test) 6. Written and witnessed informed consent to participate