Safety, Tolerability and Potential Efficacy of AVT001 in Patients With Type 1 Diabetes
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AVT001 (Treatment) Infusion of AVT001 (treatment) |
Drug: AVT001
autologous dendritic cell therapy
|
| Placebo Comparator: Matched placebo Infusion of AVT001-matched placebo |
Other: Placebo
matched placebo
|
Outcome Measures
Primary Outcome Measures
- The incidence of treatment-emergent adverse events [5 months post first dose]
Safety/tolerability outcomes
- Changes from baseline of clinical parameters on CBC/differential, chemistry panel [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, [5 months post first dose]
Safety/tolerability outcomes
Secondary Outcome Measures
- Assessment of the HLA-E-restricted CD8+ T cell regulatory activity ("potency assay") [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) [5 months post first dose]
Efficacy outcomes
- Changes from baseline in HbA1c [5 months post first dose]
Efficacy outcomes
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Joslin Diabetes Center, Harvard Medical School | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Avotres Inc.
Investigators
- Principal Investigator: Jason Gaglia, MD, Joslin Diabetes Center, Harvard Medical School
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AVT001-T1D-01