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

NCT04590872 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18279
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• 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

• Apheresis duration

  Measured in hours.

  up to 2 years

• Number of CD14+ monocytes

  Number of CD14+ monocytes collected during apheresis

  up to 2 years

• TolDC recovery after culture

  Number of TolDC generated from CD14+ monocytes

  up to 2 years

• 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 Outcomes (9)

• Change in stimulated C-peptide area under the curve

  Baseline up to 2 years of follow up

• Change in interferon (IFN)-gamma and IL-10 producing CD4+ T cells

  Baseline up to 2 years of follow up

• Change in T cell responsiveness

  Baseline up to 2 years of follow up

• Change in the number of CD8+ autoreactive T cells

  Baseline up to 2 years of follow up

• Change in immune phenotype

  Baseline up to 2 years of follow up

Study Arms (1)

Autologous Tolerogenic Dendritic Cell with Proinsulin Peptide (PIpepTolDC)

EXPERIMENTAL

After completion of leukapheresis, patients receive a prime dose of PIpepTolDC intradermally (ID) on Day 0, followed by a boost dose of PIpepTolDC ID on Day 28.

Biological: Tolerogenic Dendritic Cell Vaccine

Interventions

Tolerogenic Dendritic Cell Vaccine BIOLOGICAL

PIpepTolDCs

Autologous Tolerogenic Dendritic Cell with Proinsulin Peptide (PIpepTolDC)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Behrouz Salehian-Dardashti, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 19, 2020
• Study Start: June 16, 2022
• Primary Completion: June 3, 2024
• Study Completion (Estimated): December 15, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)