The purpose of this study is to test the safety of a novel gene viral vector treatment for adults with cocaine use disorder-sustained remission. This gene regulates an enzyme (cocaine hydrolase) that breaks down cocaine into inactive substances, thereby decreasing the pleasurable feeling this drug usually provides.
This is a phase-I dose escalation clinical trial testing the safety and MTD of IV administration of AAV8-hCocH to subjects with a history of cocaine use disorder-sustained remission. Subjects who provide written informed consent, meet entry criteria, and do not have transduction inhibition to AAV8 (pre-existing AAV8 antibodies) will be eligible. Subjects will be enrolled sequentially every 2-3 months or longer between cohorts. Dose escalation may be initiated after a single subject has been safely dosed; maximum enzyme expression is anticipated at week 3-4. This escalation paradigm is intended to minimize the number of subjects exposed to sub-therapeutic doses. The starting dose is based on the expression and safety of AAV8-CocH in mice, rats and NHP, and previous human experience using AAV8-FVIII IV in hemophilia patients. The starting dose has a large safety margin (15-fold) from the NOAEL in NHP. Approximately 7 weeks after an injection, a decision to escalate to the next dose level will be made based on a review of safety parameters and CocH levels by the investigative team.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
10
2e12 vg/kg single infusion intravenous
6e12 vg/kg single infusion intravenous
4e12 vg/kg single infusion intravenous
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Adverse Events
Number of participants with treatment-related adverse events
Time frame: 60 months
Change in enzyme expression profile
Serum level of AAV8-hCocH gene expression
Time frame: Baseline, 24 months
Maximum Observed Plasma Concentration (Cmax)
Cmax is measured as the peak concentration of AAV8 in the blood after intravenous infusion
Time frame: 24 months
Time of peak concentration (tmax)
The time to maximum plasma concentration of AAV8 in the blood after intravenous infusion
Time frame: 24 months
Half-Life (t1/2)
The time for plasma concentration of AAV8 in the blood to be reduced to exactly half of starting concentration
Time frame: 24 months
Area under the Concentration-Time Curve (AUC)
AUC is a measure of the AAV8 serum concentration over time. Used to characterize drug absorption.
Time frame: 24 months
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