Clinical trial NCT03895996: Safety, Tolerability and Potential Efficacy of AVT001 in Patients With Type 1 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Avotres Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-29
Enrollment: 25
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: At the Primary Analysis (when all the patients have completed their Day 150 visit)
measure: Number of Participants and Severity of Local i.v.-Site Reactions,
timeFrame: 5 months post first dose
measure: Changes From Baseline of Creatinine
timeFrame: 5 months post first dose
measure: Changes From Baseline of Aspartate Aminotransferase
timeFrame: 5 months post first dose
measure: Changes From Baseline of Alanine Aminotransferase
timeFrame: 5 months post first dose
measure: Changes From Baseline of Total Bilirubin
timeFrame: 5 months post first dose
Secondary outcomes:
measure: Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay")
timeFrame: 5 months post first dose
measure: 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)
timeFrame: 5 months post first dose
measure: Changes From Baseline in HbA1c
timeFrame: 5 months post first dose
Other outcomes:
Locations:
city: Boston
country: United States
facility: Joslin Diabetes Center, Harvard Medical School
state: Massachusetts
Study officials:
affiliation: Joslin Diabetes Center, Harvard Medical School
name: Jason Gaglia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaglia JL, Daley HL, Bryant NK, Ritz J, Dong T, Skyler JS, Jiang H. Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes. NEJM Evid. 2024 Jul;3(7):EVIDoa2300238. doi: 10.1056/EVIDoa2300238. Epub 2024 Jun 25.