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

NCT03895996 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AVT001-T1D-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay")

  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)

  5 months post first dose

• Changes From Baseline in HbA1c

  5 months post first dose

Study Arms (2)

AVT001 (Treatment)

EXPERIMENTAL

Infusion of AVT001 (treatment)

Drug: AVT001

Matched placebo

PLACEBO COMPARATOR

Infusion of AVT001-matched placebo

Other: Placebo

Interventions

AVT001 DRUG

autologous dendritic cell therapy

AVT001 (Treatment)

Placebo OTHER

matched placebo

Matched placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Screening hemoglobin \<10.0 g/dL; leukocytes \<3,000/uL; neutrophils \<1,500/uL; lymphocytes \<800/uL; platelets \<100,000/uL
• Screening Urine Albumin Excretion \> 300mg/gmCr
• Screening eGFR \< 60 mL/min/1.73m2
• Screening ALT or AST \> 1.5x upper limit of normal (ULN)
• Screening bilirubin \> 2.0 mg / dL, or \> 3.0 mg / dL for participants with Gilbert's Syndrome
• 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.
• Coincident medical condition likely to require immunosuppressive or immunomodulatory therapies.
• Coincident medical condition likely to limit short term (5 year) life expectancy (malignancy, symptomatic coronary artery disease, recent stroke)
• Prior radiation therapy, immunotherapy (within 1 year of screening), or chemotherapy
• Serologic evidence of current HIV-1 or HIV-2 infection
• Serologic evidence of hepatitis C infection
• Serologic evidence of acute or chronic active hepatitis B as measured by Core Ab positive and / or Surface Antibody antigen positive
• Subjects with other autoimmune conditions (except compensated or treated autoimmune thyroid, celiac, alopecia, or vitiligo diseases)
• Women who are pregnant (pregnancy testing during screening), breastfeeding, or planning pregnancy during the study period

Sponsors & Collaborators

• Avotres Inc.: lead

Study Sites (1)

Joslin Diabetes Center, Harvard Medical School

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 38916421 RESULT

Related 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.

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

Results Point of Contact

• Title: Tuochuan Dong, Director, Business & Operations
• Organization: Avotres Inc.

tuochuan.dong@avotres.com

7169093370

Study Officials

• Jason Gaglia, MD

  Joslin Diabetes Center, Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 29, 2019
• Study Start: June 20, 2019
• Primary Completion: May 17, 2022
• Study Completion: December 19, 2023
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)