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AAV8-hCocH for Cocaine Use Disorder

Primary Purpose

Cocaine Dependence, in Remission

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AAV8-hCocH

About this trial

This is an interventional other trial for Cocaine Dependence, in Remission

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Non-treatment seeking male or females ages 18 to 65 years, inclusive.
DSM-5 diagnosis of cocaine use disorder in sustained remission as confirmed by the PI's review of the medical record.
Are motivated to abstain from cocaine use during the period of the study, as evidenced both by the judgment of the Investigator or designee and by compliance with the requirement to make regular clinic visits.
In the opinion of the PI, be in good general health as determined by medical and psychiatric history, general clinical examination, vital signs, and laboratory tests.
Have provided written informed consent. Subjects should be cooperative, willing and able to participate and adhere to the protocol requirements.
Have hematology, chemistry, kidney and liver function laboratory tests that are within (+/- 10%) of the current Mayo Clinic standardized normal values.
Show a baseline EKG that demonstrates normal sinus rhythm and conduction without clinically significant abnormalities or arrhythmias.
Are willing to return to research area for follow-up.

Exclusion Criteria:

They show detectable pre-existing immunity to the AAV8 capsid as measured by AAV8 transduction inhibition and AAV8 total antibodies.
Evidence of HIV or hepatitis of any etiology.
Creatinine ≥ 1.5 mg/dL.
Any disease or mental health condition at the physician's discretion that would prevent the subject from fully complying with the requirements of the study. The physician may exclude subjects with active alcohol abuse, other substance abuse or positive urine toxicology screen for substances of abuse.
Pregnant &/or lactating. All lactating women will be excluded from study participation. Women of child-bearing potential must have a negative pregnancy test performed at screening visit, agree to use birth control throughout the study period, refrain from getting pregnant within the study period and consent to pregnancy testing throughout the study period. Men must agree to use barrier methods of birth control and refrain from fathering children within the next year.
Morbid obesity (BMI > 40).

Sites / Locations

Mayo Clinic in RochesterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

AAV8-hCocH Low dose: 2e12 vg/kg

AAV8-hCocH Medium dose: 6e12vg/kg

AAV8-hCocH High dose: 2e13 vg/kg

Arm Description

Cohort 1: Participant receives one-time IV administration of low dose 2e12 vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Cohort 2: Participant receives one-time IV administration of medium dose 6e12vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Cohort 3: Participant receives one-time IV administration of high dose 2e13 vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Outcomes

Primary Outcome Measures

Adverse Events

Number of participants with treatment-related adverse events

Change in enzyme expression profile

Serum level of AAV8-hCocH gene expression

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax)

Cmax is measured as the peak concentration of AAV8 in the blood after intravenous infusion

Time of peak concentration (tmax)

The time to maximum plasma concentration of AAV8 in the blood after intravenous infusion

Half-Life (t1/2)

The time for plasma concentration of AAV8 in the blood to be reduced to exactly half of starting concentration

Area under the Concentration-Time Curve (AUC)

AUC is a measure of the AAV8 serum concentration over time. Used to characterize drug absorption.

Full Information

NCT ID

NCT04884594

First Posted

May 7, 2021

Last Updated

October 16, 2022

Sponsor

W. Michael Hooten

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT04884594

Brief Title

AAV8-hCocH for Cocaine Use Disorder

Official Title

Intravenous Administration of AAV8-human Cocaine Hydrolase to Treat Cocaine Use Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 8, 2021 (Actual)

Primary Completion Date

December 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

W. Michael Hooten

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Dependence, in Remission

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AAV8-hCocH Low dose: 2e12 vg/kg

Arm Type

Experimental

Arm Description

Cohort 1: Participant receives one-time IV administration of low dose 2e12 vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Arm Title

AAV8-hCocH Medium dose: 6e12vg/kg

Arm Type

Experimental

Arm Description

Cohort 2: Participant receives one-time IV administration of medium dose 6e12vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Arm Title

AAV8-hCocH High dose: 2e13 vg/kg

Arm Type

Experimental

Arm Description

Cohort 3: Participant receives one-time IV administration of high dose 2e13 vg/kg of AAV8-hCocH, with 7 week of follow-up after dose

Intervention Type

Drug

Intervention Name(s)

AAV8-hCocH

Intervention Description

2e12 vg/kg single infusion intravenous

Intervention Type

Drug

Intervention Name(s)

AAV8-hCocH

Intervention Description

6e12vg/kg single infusion intravenous

Intervention Type

Drug

Intervention Name(s)

AAV8-hCocH

Intervention Description

2e13 vg/kg single infusion intravenous

Primary Outcome Measure Information:

Title

Adverse Events

Description

Number of participants with treatment-related adverse events

Time Frame

60 months

Title

Change in enzyme expression profile

Description

Serum level of AAV8-hCocH gene expression

Time Frame

Baseline, 24 months

Secondary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax)

Description

Cmax is measured as the peak concentration of AAV8 in the blood after intravenous infusion

Time Frame

24 months

Title

Time of peak concentration (tmax)

Description

The time to maximum plasma concentration of AAV8 in the blood after intravenous infusion

Time Frame

24 months

Title

Half-Life (t1/2)

Description

The time for plasma concentration of AAV8 in the blood to be reduced to exactly half of starting concentration

Time Frame

24 months

Title

Area under the Concentration-Time Curve (AUC)

Description

AUC is a measure of the AAV8 serum concentration over time. Used to characterize drug absorption.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Non-treatment seeking male or females ages 18 to 65 years, inclusive. DSM-5 diagnosis of cocaine use disorder in sustained remission as confirmed by the PI's review of the medical record. Are motivated to abstain from cocaine use during the period of the study, as evidenced both by the judgment of the Investigator or designee and by compliance with the requirement to make regular clinic visits. In the opinion of the PI, be in good general health as determined by medical and psychiatric history, general clinical examination, vital signs, and laboratory tests. Have provided written informed consent. Subjects should be cooperative, willing and able to participate and adhere to the protocol requirements. Have hematology, chemistry, kidney and liver function laboratory tests that are within (+/- 10%) of the current Mayo Clinic standardized normal values. Show a baseline EKG that demonstrates normal sinus rhythm and conduction without clinically significant abnormalities or arrhythmias. Are willing to return to research area for follow-up. Exclusion Criteria: They show detectable pre-existing immunity to the AAV8 capsid as measured by AAV8 transduction inhibition and AAV8 total antibodies. Evidence of HIV or hepatitis of any etiology. Creatinine ≥ 1.5 mg/dL. Any disease or mental health condition at the physician's discretion that would prevent the subject from fully complying with the requirements of the study. The physician may exclude subjects with active alcohol abuse, other substance abuse or positive urine toxicology screen for substances of abuse. Pregnant &/or lactating. All lactating women will be excluded from study participation. Women of child-bearing potential must have a negative pregnancy test performed at screening visit, agree to use birth control throughout the study period, refrain from getting pregnant within the study period and consent to pregnancy testing throughout the study period. Men must agree to use barrier methods of birth control and refrain from fathering children within the next year. Morbid obesity (BMI > 40).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Brenda Anderson, RN

Phone

(507) 255-7157

Hooten.william@mayo.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

W. Michael Hooten, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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AAV8-hCocH for Cocaine Use Disorder

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