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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 17, 2022

Interventions

  • Drug: AVT001
    • autologous dendritic cell therapy
  • Other: Placebo
    • matched placebo

Arms, Groups and Cohorts

  • Experimental: AVT001 (Treatment)
    • Infusion of AVT001 (treatment)
  • Placebo Comparator: Matched placebo
    • Infusion of AVT001-matched placebo

Clinical Trial Outcome Measures

Primary Measures

  • The incidence of treatment-emergent adverse events
    • Time Frame: 5 months post first dose
    • Safety/tolerability outcomes
  • Changes from baseline of clinical parameters on CBC/differential, chemistry panel
    • Time Frame: 5 months post first dose
    • Safety/tolerability outcomes – the clinical parameters tested include creatinine, AST, ALT, and total bilirubin
  • The incidence and severity of local i.v.-site reactions,
    • Time Frame: 5 months post first dose
    • Safety/tolerability outcomes

Secondary Measures

  • Assessment of the HLA-E-restricted CD8+ T cell regulatory activity (“potency assay”)
    • Time Frame: 5 months post first dose
    • Efficacy outcomes – “potency assay” measures the activity of CD8+ T regulatory cells
  • 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
    • Efficacy outcomes
  • Changes from baseline in HbA1c
    • Time Frame: 5 months post first dose
    • Efficacy outcomes

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Avotres Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jason Gaglia, MD, Principal Investigator, Joslin Diabetes Center, Harvard Medical School

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