Clinical trial NCT04590872: An Immunotherapy Vaccine (PIpepTolDC) for the Treatment of Patients With Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 2 years
measure: Apheresis duration
timeFrame: up to 2 years
measure: Number of CD14+ monocytes
timeFrame: up to 2 years
measure: TolDC recovery after culture
timeFrame: up to 2 years
measure: Number of successful manufactured products
timeFrame: Up to 2 years
Secondary outcomes:
measure: Change in stimulated C-peptide area under the curve
timeFrame: Baseline up to 2 years of follow up
measure: Change in interferon (IFN)-gamma and IL-10 producing CD4+ T cells
timeFrame: Baseline up to 2 years of follow up
measure: Change in T cell responsiveness
timeFrame: Baseline up to 2 years of follow up
measure: Change in the number of CD8+ autoreactive T cells
timeFrame: Baseline up to 2 years of follow up
measure: Change in immune phenotype
timeFrame: Baseline up to 2 years of follow up
measure: Change in islet autoantibodies
timeFrame: Baseline up to 2 years of follow up
measure: Change in glycosylated hemoglobin A1c (HbA1c) levels
timeFrame: Baseline up to 2 years of follow up
measure: Change in exogenous insulin use (units/kg)
timeFrame: Baseline up to 2 years of follow up
measure: Change in blood glucose levels
timeFrame: Baseline up to 2 years of follow up
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Behrouz Salehian-Dardashti, MD
role: PRINCIPAL_INVESTIGATOR
References: