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

Type 1 Diabetes Mellitus Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03895996
• Other study ID #: AVT001-T1D-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 20, 2019
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: Avotres Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: December 2023
• Est. primary completion date: May 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• AVT001
autologous dendritic cell therapy

Other:
• Placebo
matched placebo

Locations

Country	Name	City	State
United States	Joslin Diabetes Center, Harvard Medical School	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Avotres Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of treatment-emergent adverse events	Safety/tolerability outcomes	5 months post first dose
Primary	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
Primary	The incidence and severity of local i.v.-site reactions,	Safety/tolerability outcomes	5 months post first dose
Secondary	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
Secondary	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
Secondary	Changes from baseline in HbA1c	Efficacy outcomes	5 months post first dose