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

• ClinicalTrials.gov Identifier: NCT03895996
• Recruitment Status: Active, not recruiting
• First Posted: March 29, 2019
• Last Update Posted: December 12, 2022
• Sponsor: Avotres Inc.
• Information provided by (Responsible Party): Avotres Inc.

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
Type 1 Diabetes Mellitus	Drug: AVT001; Other: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 20, 2019
• Actual Primary Completion Date: May 17, 2022
• Estimated Study Completion Date: December 2023

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 :

1. The incidence of treatment-emergent adverse events [ Time Frame: 5 months post first dose ]
   Safety/tolerability outcomes
2. 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
3. The incidence and severity of local i.v.-site reactions, [ Time Frame: 5 months post first dose ]
   Safety/tolerability outcomes

Secondary Outcome Measures :

1. 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
2. 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
3. Changes from baseline in HbA1c [ Time Frame: 5 months post first dose ]
   Efficacy outcomes

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

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

More Information

• Responsible Party: Avotres Inc.
• ClinicalTrials.gov Identifier: NCT03895996
• Other Study ID Numbers: AVT001-T1D-01
• First Posted: March 29, 2019
• Last Update Posted: December 12, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases