An Immunotherapy Vaccine (PIpepTolDC) for the Treatment of Patients With Type 1 Diabetes

Inclusion criteria

• Willingness to undergo leukapheresis
• Willingness to be followed for about 2 years post-prime dose
• For participants who have a personal continuous glucose monitoring device (CGMD): Willingness to wear a second CGMD during mandated study CGMD visits
• Diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria
• Historical presence of at least one type-1 diabetes associated autoantibody

• GAD specific autoantibodies (glutamic acid decarboxylase autoantibodies [GADA])
• Islet cell cytoplasmic autoantibodies (ICA)
• Islet-antigen 2 specific autoantibody (IA-2A)
• Zinc transporter 8 specific autoantibody (ZNT8A); and/or
• Insulin autoantibody (IAA) (must have been obtained within 7 days of initiating exogenous insulin replacement therapy)
• Time from diagnosis to screening mixed meal tolerance test (MMTT) must be >= 1 year but =< 4 years
• Stable glycemic control per participant's physician
• HbA1c =< 7.5% (=< 58 mmol/mol)
• Non-fasting C-peptide > 0.017 nmol/L
• Stimulated peak C-peptide levels > 0.2 nmol/L from a 2-hour screening MMTT
• Positive for *04:01 allele, *04:02 allele and/or *04:04 allele at the human leukocyte antigen (HLA)-DRB1 gene locus
• Does not possess the protective HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype
• Adequate self-assessment of blood glucose values and recording of glucose values, and administered insulin doses as deemed sufficient by the participant's physician
• No diagnosis of type 1 diabetes related microvascular/macrovascular complications (e.g. nephropathy, retinopathy and neuropathy)
• Deemed acceptable for autologous cell collection (i.e. leukapheresis)
• Only for those who are naive to CGMD use: Deemed able to correctly use a CGM device following training session with a certified diabetes educator and manufacturer representative
• Must meet organ function criteria

Exclusion criteria

• Other investigational agents, biologics
• Anti-inflammatory therapy

• Exception: Over-the-counter (OTC) anti-inflammatory agents (e.g. ibuprofen, Tylenol) are generally allowed. However, those requiring chronic OTC anti-inflammatory agents and unable to stop during mandated CGMD study visits will be excluded
• Systemic corticosteroids within 28 days prior to leukapheresis
• Systemic immunosuppressive therapy (e.g. cyclosporine-A, cyclophosphamide)
• Monoclonal antibody therapy
• Allergen immunotherapy within 28 days prior to leukapheresis
• Vaccine(s) within 28 days prior to leukapheresis
• Prior allogeneic organ transplant
• Beta-cell stimulants (e.g. sulfonylureas such as glimepiride), glucagon-like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors (exception: Those with acute exposure to these agents during T1D misdiagnosis may be permitted per PI discretion)
• Insulin sensitizers (e.g. metformin, thiazolidinediones) within 2 months of leukapheresis
• History of insulin sensitizer use (e.g. metformin, thiazolidinediones) ≥ 2 months
• Other autoimmune/inflammatory disorders (exceptions: (i) Type 1 diabetes. (ii) Asymptomatic patients with incidental autoantibody titres may be permitted per PI discretion)
• Other autoimmune/inflammatory disorders (exception type 1 diabetes)
• Active infection requiring antibiotics and/or anti-virals
• Known history of HIV, HBV, HCV, HTLV, syphilis
• History of positive purified protein derivative (PPD) skin test
• History of atopy requiring systemic treatment and/or history of severe allergic reactions
• History or current malignancy
• Unstable cardiac disease
• History of vascular disease (e.g. deep vein thrombosis, stroke)
• Clinically significant uncontrolled illness
• Females only: pregnant or breastfeeding