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NCT Number: NCT03895996

Safety, Tolerability and Potential Efficacy of 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.

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Key information

Conditions

Type 1 Diabetes Mellitus Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Joslin Diabetes Center, Harvard Medical School

Boston, Massachusetts, 02215, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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
  • Inadequate venous access to support leukapheresis
  • Any condition that in the opinion of the investigator(s) would preclude the subject from participating in a clinical trial.
  • Abnormal screening ECG that in the opinion of the investigator or sponsor would pose a safety risk.

Treatment and study plan

AVT001

Drug

autologous dendritic cell therapy

Placebo

Other

matched placebo

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAE)

    Time frame: At the Primary Analysis (when all the patients have completed their Day 150 visit)

    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.

  2. Number of Participants and Severity of Local i.v.-Site Reactions,

    Time frame: 5 months post first dose

    Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported.

  3. Changes From Baseline of Creatinine

    Time frame: 5 months post first dose

    Safety/tolerability outcomes - creatinine

  4. Changes From Baseline of Aspartate Aminotransferase

    Time frame: 5 months post first dose

    Safety/tolerability outcomes - Aspartate Aminotransferase

  5. Changes From Baseline of Alanine Aminotransferase

    Time frame: 5 months post first dose

    Safety/tolerability outcomes - Alanine Aminotransferase

  6. Changes From Baseline of Total Bilirubin

    Time frame: 5 months post first dose

    Safety/tolerability outcomes - Total Bilirubin

Secondary outcomes

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

    Time frame: 5 months post first dose

    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.

  2. 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)

    Time frame: 5 months post first dose

    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.

  3. Changes From Baseline in HbA1c

    Time frame: 5 months post first dose

    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.

Sponsors and collaborators

Lead sponsor

Avotres Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2022
Study completion
2023
First posted
Mar 29, 2019
Registry last updated
Mar 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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