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
Overview
- Phase
- Phase 1
- Intervention
- AVT001
- Conditions
- Type 1 Diabetes Mellitus
- Sponsor
- Avotres Inc.
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events (TEAE)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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.
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
Arms & Interventions
AVT001 (Treatment)
Infusion of AVT001 (treatment)
Intervention: AVT001
Matched placebo
Infusion of AVT001-matched placebo
Intervention: Placebo
Outcomes
Primary Outcomes
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.
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.
Changes From Baseline of Creatinine
Time Frame: 5 months post first dose
Safety/tolerability outcomes - creatinine
Changes From Baseline of Aspartate Aminotransferase
Time Frame: 5 months post first dose
Safety/tolerability outcomes - Aspartate Aminotransferase
Changes From Baseline of Alanine Aminotransferase
Time Frame: 5 months post first dose
Safety/tolerability outcomes - Alanine Aminotransferase
Changes From Baseline of Total Bilirubin
Time Frame: 5 months post first dose
Safety/tolerability outcomes - Total Bilirubin
Secondary Outcomes
- 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)