Dendritic Cells for Type 1 Diabetes Mellitus (T1DM) Therapy

Autologous Co-stimulation-impaired Dendritic Cells for Type 1 Diabetes Mellitus (T1DM) Therapy: A Sequential Open Label Phase IB Safety Assessment/ Randomized, Double-blind Phase IIA Efficacy Trial to Maintain and Improve Functional Beta Cell Mass in New Onset Disease T1DM Patients

Phase IB will evaluate the safety of autologous, ex vivo-engineered, co-stimulation impaired dendtritic cells to maintain and improve functional residual beta cell mass in new onset Type I Diabetes Mellitus (T1DM) patients. Efficacy measures will be collected and summarized.

Phase IIA will evaluate the safety and efficacy of 3 randomized treatment groups in new onset T1DM patients to assess if the antisense DNA-treated co-stimulation-impaired immunoregulatory dendritic cells (iDC) will safely preserve and/or increase B-cell mass resulting in improvement and/or normalization of blood glucose levels and glycated hemoglobin A1c.

Study Overview

• Status: Unknown
• Conditions: Treatment of Type I Diabetes Mellitus.
• Intervention / Treatment: Biological: Biological

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Orville G. Kolterman, MD; Phone Number: 7242085707; Email: okolterman@alumnistandford.edu
• Study Contact Backup: Name: Peter Gregoire, MBA; Phone Number: 7242085707; Email: pgregoire@futurelifesourcesllc.org

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
      • Principal Investigator: Mary Korytokowski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:(both open label phase IB safety and Phase IIA study):

1. Patients with new onset T1DM (>18 years of age for the phase IB and then >16 (first 10 subjects), >12 years of age for the second 10 subjects, > 8 years for the next 10 subjects and, finally, >8 years of age for the remainder of the phase IIA patients) within 6 months of diabetes mellitus diagnosis.
2. Evidence of decreased β-cell function as measured by C-peptide and blood glucose levels consistent with impaired glucose tolerance.
3. Evidence of at least one high-risk HLA haplotype.
4. Evidence of at least one diabetes-related autoantibody (e.g. IA-2, GAD, ZnT8) ,
5. Adequate immune competence as assessed by immunoreactivity to alloantigens in mixed leukocyte culture and reactivity to viral antigens (CEF Pool Assay) in vitro.
6. Normal hematologic, liver and kidney function.
7. Female participants of childbearing potential in this study must agree to use an effective form of 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) with spermicide], or surgical sterilization (vasectomy for male partner, tubal ligation or hysterectomy). Sexually active male participants must agree to use an effective form of birth control such as condoms.

Exclusion Criteria:(both open label phase IB safety and Phase IIA study):

1. Enrollment or history of enrollment in a drug, or biologic therapy study sponsored by TrialNet.
2. A significant history or current evidence of cardiac disease, uncontrolled hypertension, serious arrhythmias.
3. Evidence of active infection requiring antibiotic therapy.
4. History of other concurrent significant medical diseases.
5. Pregnant or lactating women.
6. Patients requiring chronic systemic corticosteroids.
7. Any other immune disorder including but not limited to other autoimmune diseases, HIV, HBV, HCV, HPV, HSV positivity.
8. Impaired renal function with a creatinine level > 1.5.
9. Administration of the following therapies while patients are undergoing treatment on this protocol: i) radiation therapy; ii) chemotherapy; iii) corticosteroids (except when administered in life-threatening circumstances); iv) other particle or cell-based therapies; v) other biologic therapies; vi) other therapies aimed at modulating the immune system; vii) other endocrine-related therapies, hormone replacement (other than thyroxine and contraceptive), glucoregulation.
10. A hemaglobinopathy known to interfere with the ability to accurately determine HbA1c.
11. No prior radiation therapy, immunotherapy, or chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iDC recipients; iDC cells modified by in vitro engineering.	Biological: Biological
Active Comparator: Control DC recipients; DC cells which have not been modified.	Biological: Biological
Placebo Comparator: Placebo recipients; Saline injections.	Biological: Biological

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of treatment-emergent adverse events.	Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
2-hour area under the curve (AUC) average of C-peptide at 12 months after completion of administration of assigned therapy (Protocol Month 15).	12 Months

Collaborators and Investigators

• Sponsor: DiaVacs, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: September 18, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 20, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: October 22, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: DV-0100-100