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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: AVT001
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVT001 (Treatment)<br>Infusion of AVT001 (treatment) | Drug: AVT001<br>* autologous dendritic cell therapy<br>|
| Placebo Comparator: Matched placebo<br>Infusion of AVT001-matched placebo | Other: Placebo<br>* matched placebo<br>|

What is the study measuring?
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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 |