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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Pilot Study to Evaluate the Safety and Feasibility of Autologous Tolerogenic Dendritic Cells Loaded With Proinsulin Peptide (C19-A3) in Patients With Type 1 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04590872
• Other study ID #: 18279
• Status: Recruiting
• Phase: Phase 1
• Start date: June 16, 2022
• Est. completion date: December 10, 2024

Study information

• Verified date: June 2024
• Source: City of Hope Medical Center
• Contact: Study Coordinator
• Phone: 866-444-7538
• Email: DL-TolDC[@]coh.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial investigates the side effects of PIpepTolDC vaccine in treating patients with type 1 diabetes who use insulin and don't have any other diabetes-related health complications. Type 1 diabetes is an autoimmune disease. This means that the immune system, which usually protects against foreign invaders like bacteria and viruses, attacks the body's insulin-producing betacells in the pancreas (autoimmune response). Overtime, the beta cells are destroyed by the immune system. To stay alive, people with type 1 diabetes must use insulin. PIpepTolDC vaccine is a type of immunotherapy (a treatment that uses a person's own immune system) that works like an allergy shot. The vaccine is made using one's own immune cells (dendritic cells) and a beta cell protein. The vaccine may teach the immune system to stop attacking the beta cells, which may help the beta cells recover and make enough insulin to control blood sugar levels. The vaccine may also help reduce future type 1 diabetes related complications.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7
• Est. completion date: December 10, 2024
• Est. primary completion date: December 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Biological:
• Tolerogenic Dendritic Cell Vaccine
PIpepTolDCs

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
City of Hope Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events	Toxicity and adverse events (except hypoglycemia and diabetic ketoacidosis [DKA]) will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Hypoglycemia events and DKA will be defined per American Diabetes Association (ADA) grading systems.Observed toxicities will be summarized by type, severity (by CTCAE v 5.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.	Up to 2 years
Primary	Apheresis duration	Measured in hours.	up to 2 years
Primary	Number of CD14+ monocytes	Number of CD14+ monocytes collected during apheresis	up to 2 years
Primary	TolDC recovery after culture	Number of TolDC generated from CD14+ monocytes	up to 2 years
Primary	Number of successful manufactured products	Number of manufactured products that meet the required cell dose/day, sterility (e.g. endotoxin and gram staining), and viability compared to the total number of products manufactured.	Up to 2 years
Secondary	Change in stimulated C-peptide area under the curve	Assessed via 2-hr mixed meal tolerance test (MMTT). C-peptide preservation is defined as the maintenance of baseline C-peptide levels.	Baseline up to 2 years of follow up
Secondary	Change in interferon (IFN)-gamma and IL-10 producing CD4+ T cells	Will be assessed in response to pro-insulin peptide C19-A3, and assessed via cytokine enzyme-linked immunosorbent spot assay.	Baseline up to 2 years of follow up
Secondary	Change in T cell responsiveness	Will assess for changes in T cell responsiveness to pro-insulin peptide C19-A3 compared to other antigens. Assessed via Lymphocyte Simulation Test.	Baseline up to 2 years of follow up
Secondary	Change in the number of CD8+ autoreactive T cells	Assessed via quantum dot (Q-DOT) nanotechnology assay.	Baseline up to 2 years of follow up
Secondary	Change in immune phenotype	Will analyze for changes in immune cell populations via flow cytometry	Baseline up to 2 years of follow up
Secondary	Change in islet autoantibodies	Will analyze for changes in IAA, GAA, IA-2A, ZnT8A via enzyme-linked immunosorbent assay.	Baseline up to 2 years of follow up
Secondary	Change in glycosylated hemoglobin A1c (HbA1c) levels	HbA1c levels will be assessed via blood test	Baseline up to 2 years of follow up
Secondary	Change in exogenous insulin use (units/kg)	Insulin usage will be recorded daily from the insulin pump and/or participant insulin use logs. The mean daily insulin usage over the 10 consecutive days (IU units/kg body weight/day) preceding the clinic visit will be calculated for each participant.	Baseline up to 2 years of follow up
Secondary	Change in blood glucose levels	Will include clinically important/severe hypoglycemia, hyperglycemia and DKA events as assessed by ADA grading systems. Levels of glucose will be assessed from bloods samples taken during the MMTT and from insulin pump/participant insulin logs	Baseline up to 2 years of follow up