Autologous Immunoregulatory Dendritic Cells for Type 1 Diabetes Therapy

NCT02354911 | Withdrawn Phase 2 DMC

• 1 other identifier: DV-0100-101
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine whether dendritic cells collected via leukapheresis and incubated with antisense DNA oligonucleotides and then injected back into the same subject will serve as modulators of the immune system in a manner that disrupts the autoimmune process responsible for the destruction of pancreatic beta cells in subjects with new onset type 1 diabetes.

Conditions

Type 1 Diabetes

Keywords

Immunomodulation

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the mean 2-hour area under the curve (AUC) for plasma c-peptide at 12 and 24 months

  Mean 2-hour area under the time-concentration curve for plasma c-peptide following ingestion of a standardized mixed meal compared across treatment groups at end of Segment 1 (12 months) and Segment 2 (24 months)

  12 and 24 months

Secondary Outcomes (9)

• Reported adverse events

  12 months; 12 to 24 months and 0 to 24 months

• Change from baseline in number of potentially-tolerogenic/regulatory T-cells, B-cells and dendritic cells in circulating peripheral blood mononuclear cell fraction

  3,6,9,12,15,18,21 and 24 months

• Change from baseline in sub-populations of T-cells

  3,6,9,12,15,18,21 and 24 months

• Change from baseline in sub-populations of B-cells

  3,6,9,12,15,18,21 and 24 months

• Change from baseline in sub-populations of dendritic cells

  3,6,9,12,15,18,21 and 24 months

Study Arms (2)

Immunoregulatory Dendritic Cells (iDC)

EXPERIMENTAL

Biological intervention consisting of autologous dendritic cells treated in vitro to convert to active immunoregulatory dendritic cells.

Biological: Immunoregulatory Dendritic Cells

Placebo Control

PLACEBO COMPARATOR

Saline injections administered blinded to subject and all study staff except for research pharmacist who is not involved in study conduct

Other: Placebo Comparator: Placebo Control

Interventions

Immunoregulatory Dendritic Cells BIOLOGICAL

Autologous dendritic cells harvested by leukapheresis and engineered ex vivo via incubation with antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80 and CD86. The ex vivo engineered product is then administered via blinded intradermal injection in the peri-umbilical region of the abdomen given as 4 separate injections at 2-week intervals (\~10 million cells/injection).

Also known as: iDC

Immunoregulatory Dendritic Cells (iDC)

Placebo Comparator: Placebo Control OTHER

Blinded intradermal injections in the peri-umbical region of the abdomen given as 4 separate injections at 2-week intervals

Placebo Control

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Fully executed, Institutional Review Board (IRB) approved, informed consent form
• New onset type 1 diabetes randomized within 100 days of diagnosis
• Positive for at least one islet cell auto-antibody; GAD, insulin (if sample within 7 days of the onset of insulin therapy), islet antibody 2 (IA-2), zinc transporter 8 antibody (ZnT8), and/or islet cell antibody (ICA)
• Peak plasma c-peptide concentration \>0.2 pmol/mL after ingestion of a standardized mixed meal
• Serologic evidence of prior Epstein-Barr virus (EBV) infection
• Immunoreactivity to alloantigens in mixed leukocyte culture and reactivity to viral antigens (CEF Pool Assay) in vitro
• Adequate peripheral venous access for leukapheresis
• Female participants with childbearing potential must agree to use effective birth control during study participation. Reliable and effective forms of birth control include: true abstinence, intrauterine device (IUD), hormonal-based contraception, double-barrier contraception (condom or occlusive cap (diaphragm or cervical cap) + spermicide, or surgical sterilization (vasectomy for male partner, tubal ligation or hysterectomy).
• Sexually active male participants must agree to use condoms during intercourse

You may not qualify if:

• History of enrollment in a drug, or biologic therapy clinical trial within past 12 months impacting the immune system
• Prior or current therapy known to cause a significant, ongoing change in the course of type 1 diabetes or immune status
• Leukopenia (\<3,000 leukocytes/microliter, neutropenia (\<1,500 neutrophils/microliter), lymphopenia (\<800 lymphocytes/microliter) or thrombocytopenia (\<125,000 platelets/microliter)
• Positive screen for HIV, tuberculosis, hepatitis B, hepatitis C, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) infection
• Vaccination with any live vaccine product within the 3 months prior to the first cycle of study agent administration
• Female subjects pregnant or unwilling to defer pregnancy for the study period
• Females lactating at screening
• History of significant heart disease (e.g., myocardial infarction, coronary artery disease, angina pectoris, arrhythmia, uncontrolled hypertension, congestive heart failure, structural defects)
• Liver disease with alanine transaminase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal
• Impaired renal function with a serum creatinine concentration \> 1.5.
• Any other significant immune disorder including, but not limited to, rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, vitiligo, ankylosing spondylitis and celiac disease. (Thyroiditis treated with a stable dose of thyroid replacement therapy is allowed.)
• Any condition that interferes with accurate measurement of glycated hemoglobin (hemoglobin A1C)
• Any condition that, in the investigator's opinion, may compromise continuous study participation or confound study results
• Any planned vaccinations scheduled prior to end of study participation
• Chronic treatment with systemic corticosteroids (topical or inhaled corticosteroids are allowed)

Sponsors & Collaborators

• DiaVacs, Inc.: lead
• West Penn Allegheny Health System: collaborator
• University of Pittsburgh Medical Center: collaborator
• Stanford University: collaborator
• University of Miami: collaborator

Related Publications (1)

• Phillips BE, Garciafigueroa Y, Engman C, Trucco M, Giannoukakis N. Tolerogenic Dendritic Cells and T-Regulatory Cells at the Clinical Trials Crossroad for the Treatment of Autoimmune Disease; Emphasis on Type 1 Diabetes Therapy. Front Immunol. 2019 Feb 6;10:148. doi: 10.3389/fimmu.2019.00148. eCollection 2019.

  PMID: 30787930 DERIVED

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

• Massimo Trucco, PhD

  Institue of Cellular Therapeutics, Allegheny General Hospital, Pittsburgh, PA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: February 3, 2015
• Study Start: October 1, 2015
• Primary Completion: February 16, 2024
• Study Completion: February 16, 2024
• Last Updated: February 20, 2024

Record last verified: 2024-02