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: Active, not recruiting
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: AVT001; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 24
• 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
• Genders Eligible for Study: All

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
The incidence of treatment-emergent adverse events	Safety/tolerability outcomes	5 months post first dose
Changes from baseline of clinical parameters on CBC/differential, chemistry panel	Safety/tolerability outcomes - the clinical parameters tested include creatinine, AST, ALT, and total bilirubin	5 months post first dose
The incidence and severity of local i.v.-site reactions,	Safety/tolerability outcomes	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")	Efficacy outcomes - "potency assay" measures the activity of CD8+ T regulatory cells	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)	Efficacy outcomes	5 months post first dose
Changes from baseline in HbA1c	Efficacy outcomes	5 months post first dose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2019
• Primary Completion (Actual): May 17, 2022
• Study Completion (Anticipated): December 1, 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): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

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: 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