Safety, Tolerability and Potential Efficacy of AVT001 in Patients With Type 1 Diabetes

A Phase 1 / 2 Double-Blind, Randomized, Placebo Controlled Study of Safety, Tolerability and Potential Efficacy of AVOTRES Cell-Based Therapy (AVT001) in Patients With Type 1 Diabetes

This is a double-blind, randomized , placebo-controlled study to evaluate the safety and tolerability of AVT001, and to assess AVT001 as a potential treatment for type 1 diabetes (T1D). The trial will involve approximately 24 new-onset T1D subjects.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: AVT001; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center, Harvard Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosis of type 1 diabetes, within 12 months of first dosing, confirmed by positive lab result for one or more of the following types of autoantibodies:

   1. Glutamic acid decarboxylase (GAD65)
   2. Insulinoma associated protein 2 (IA-2, also known as ICA-512)
   3. Zinc transporter 8 (ZnT8).
2. Age 16 or older and able to provide informed consent/assent.
3. If a participant is female with reproductive potential, willing to avoid pregnancy through the duration of the trial.
4. Signed and dated written informed consent/assent.

Key Exclusion Criteria:

1. Poorly controlled diabetes despite insulin therapy, who in the opinion of the investigator would not be a good candidate for participation in a clinical trial
2. Screening hemoglobin <10.0 g/dL; leukocytes <3,000/uL; neutrophils <1,500/uL; lymphocytes <800/uL; platelets <100,000/uL
3. Screening Urine Albumin Excretion > 300mg/gmCr
4. Screening eGFR < 60 mL/min/1.73m2
5. Screening ALT or AST > 1.5x upper limit of normal (ULN)
6. Screening bilirubin > 2.0 mg / dL, or > 3.0 mg / dL for participants with Gilbert's Syndrome
7. Current use of immunosuppressive or immunomodulatory therapies, including pharmacologic doses of systemic steroids. However, topical steroidal creams and inhaled steroids without large systemic absorption are allowed.
8. Coincident medical condition likely to require immunosuppressive or immunomodulatory therapies.
9. Coincident medical condition likely to limit short term (5 year) life expectancy (malignancy, symptomatic coronary artery disease, recent stroke)
10. Prior radiation therapy, immunotherapy (within 1 year of screening), or chemotherapy
11. Serologic evidence of current HIV-1 or HIV-2 infection
12. Serologic evidence of hepatitis C infection
13. Serologic evidence of acute or chronic active hepatitis B as measured by Core Ab positive and / or Surface Antibody antigen positive
14. Subjects with other autoimmune conditions (except compensated or treated autoimmune thyroid, celiac, alopecia, or vitiligo diseases)
15. Women who are pregnant (pregnancy testing during screening), breastfeeding, or planning pregnancy during the study period
16. Inadequate venous access to support leukapheresis
17. Any condition that in the opinion of the investigator(s) would preclude the subject from participating in a clinical trial.
18. Abnormal screening ECG that in the opinion of the investigator or sponsor would pose a safety risk.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVT001 (Treatment); Infusion of AVT001 (treatment)	Drug: AVT001; autologous dendritic cell therapy
Placebo Comparator: Matched placebo; Infusion of AVT001-matched placebo	Other: Placebo; matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAE)	Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose.	At the Primary Analysis (when all the patients have completed their Day 150 visit)
Number of Participants and Severity of Local i.v.-Site Reactions,	Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported.	5 months post first dose
Changes From Baseline of Creatinine	Safety/tolerability outcomes - creatinine	5 months post first dose
Changes From Baseline of Aspartate Aminotransferase	Safety/tolerability outcomes - Aspartate Aminotransferase	5 months post first dose
Changes From Baseline of Alanine Aminotransferase	Safety/tolerability outcomes - Alanine Aminotransferase	5 months post first dose
Changes From Baseline of Total Bilirubin	Safety/tolerability outcomes - Total Bilirubin	5 months post first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay")	CD8+ T cell Inhibition Assay is used to determine whether AVT001 corrects the defect of the dysfunctional Q/E CD8+ Treg pathway in T1D patients. More specifically, this assay detects the specific recognition between the TCR on patients' Q/E CD8+Treg cells and the "common target structure", the HLA-E/Hsp60sp complex, expressed on the surface of the artificially established target cells. The % inhibition measures the function of down-regulation by Q/E CD8+ Tregs via comparing the % of inhibition of TH1 cells versus TB1 cells. By assessing the % inhibition of the TH1 cells of the patient's CD8+ T cells, the CD8+ T cell Inhibition Assay detects the specific recognition of the common target structure (HLA-E/Hsp60sp) on TH1 cells by the TCR on the patient's T cells to be tested. A negative value means the measured Q/E CD8+ Tregs completely lose its inhibition function, and the TH1 cells cultured with it happened to grow faster than the corresponding TB1 cells as its control.	5 months post first dose
Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT)	The area under the stimulated C-peptide curve (AUC) over the first 4-hour period of a mixed meal glucose tolerance test is calculated using the trapezoidal rule that is a weighted sum of the C-peptide values over the 240 minutes. The AUC is normalized by dividing it with 240 mins, therefore, its unit is nmol/L. Missing C-peptide levels at any given timepoint is not imputed. In the calculation of the AUC when C-peptide levels are missing, a line is drawn from the last timepoint with a non-missing C-peptide to the next timepoint with non-missing C-peptide.	5 months post first dose
Changes From Baseline in HbA1c	HbA1c is a blood test that is used to monitor blood glucose control in people with diabetes. HbA1c is short for glycated haemoglobin. The test is also sometimes called haemoglobin A1c.	5 months post first dose

Collaborators and Investigators

• Sponsor: Avotres Inc.
• Investigators: Principal Investigator: Jason Gaglia, MD, Joslin Diabetes Center, Harvard Medical School

Publications and helpful links

General Publications

• Gaglia JL, Daley HL, Bryant NK, Ritz J, Dong T, Skyler JS, Jiang H. Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes. NEJM Evid. 2024 Jul;3(7):EVIDoa2300238. doi: 10.1056/EVIDoa2300238. Epub 2024 Jun 25.

Helpful Links

• Avotres Inc. in collaboration with Joslin Diabetes Center, a Harvard Medical School affiliate, have reported one year data of a phase I/II clinical trial of AVT001 in type 1 diabetes.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: AVT001-T1D-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No