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Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals

Primary Purpose

Cocaine Dependence

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
dAd5GNE Vaccine
Placebo
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cocaine Dependence focused on measuring cocaine vaccine, cocaine dependence, Cocaine

Eligibility Criteria

21 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Accrual will be random, with no bias as to gender or racial/ethnic group. Because the accrual process will be random, it is possible that there may be differences in the proportion of males and females, and racial/ethnic groups among the study individuals. All subjects will be concurrently participating in behavioral therapy programs run by Dr. Beeder's clinical team. Each case will be reviewed with the Eligibility Committee, comprised of three investigators other than the PI, to determine eligibility. The Principal Investigator will not participate in this process.

All subjects must fulfill all inclusion criteria and none of the exclusion criteria in order to participate in this study.

Inclusion Criteria:

  1. All subjects should be able to provide informed consent.
  2. Must provide HIV informed consent.
  3. Males and females, 21- 69 years of age.
  4. Individuals that have been diagnosed with a cocaine use disorder according to DSM-V-TR criteria, with documented evidence of cocaine use within the past 60 days and have previously used an average of 1 to 10 grams of powdered and/or crack cocaine (via insufflation or smoking only) per week. Any prior 1 to 4 month period of cocaine abstinence in the past year will be excluded when calculating average cocaine use to evaluate study eligibility.

6. Fertile males and females must agree to use adequate forms of contraception for the duration of the entire study.

7. Body weight > 45 kg.

Exclusion Criteria:

  1. Individuals not deemed in good overall health by the investigator.
  2. Diagnosed history of severe psychotic disorders.
  3. Abnormal EKG at screening with changes consistent with cardiac disease.
  4. History of significant cardiovascular disease, hypertension, prior myocardial infarction and/or cerebrovascular event.
  5. Individuals who are currently on beta-blockers.
  6. Physical signs or laboratory values suggestive of systemic disorders.
  7. History of attempted suicide, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) and/or committed homicide.
  8. History of diagnosed obsessive compulsive disorder (OCD).
  9. Known allergy to soy.
  10. Individuals who are currently taking alprazolam (Xanax) or ziprasidone (Geodon).
  11. Evidence of active infection of any types, including COVID-19, or positive for human immunodeficiency virus (HIV).
  12. Historical or current use of immunomodulators or immunosuppressants <5 years prior to screening.
  13. Receipt of blood within 3 months of screening.
  14. Females who are pregnant or nursing.
  15. Concurrent participation in any other FDA approved Investigational New Drug.
  16. Abnormal liver function (transaminases greater than 2x the upper limit of normal values)
  17. eGFR <30 mL/min/1.73 m2
  18. Severe substance use disorder based on DSM-V-TR criteria (excluding cocaine, nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment) currently not in remission according to one of the following criteria:

    • Early Full Remission: This specifier is used if none of the criteria for Dependence or Abuse have been met for at least 1 month, but less than 12 months OR
    • Early Partial Remission: This specifier is used if only one or more (but not all) of the criteria for Dependence or Abuse has/have been met for at least 1 month, but less than 12 months. OR
    • Sustained Full Remission: This specifier is used if none of the criteria for Dependence or Abuse have been met at any time during a period of 12 months or longer OR
    • Sustained Partial Remission: This specifier is used if only one or more (but not all) of the criteria for Dependence or Abuse has/have been met for a period of 12 months or longer OR
    • On Agonist Therapy: This specifier is used if the individual is on a prescribed agonist medication, and none of the criteria for Dependence or Abuse has been met for that class of medication for at least the past month (except tolerance to, or withdrawal from, the agonist). This category also applies to those being treated for Dependence using a partial agonist or an agonist/antagonist OR
    • Substance Use Related Disorder (mild) up to two disorders: Patients that are assessed to have mild substance-use-related disorders according to the DSM-V criteria will be allowed to participate in the study as long as the number of the disorder-resulting substances does not exceed two (with the exception of the nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment).
  19. History of any seizure disorder.
  20. Individuals with history of Guillain-Barré Syndrome.
  21. Diagnosis of >2 Substance Use Related Disorders (mild) based on DSM-V- TR criteria (excluding nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment
  22. On a prescribed agonist medication, with criteria for dependence or abuse for that class ofmedication for at least the past month (except tolerance to, or withdrawal from, the agonist

Sites / Locations

  • WCMC Department of Genetic MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Cohort 1: 100µg

Cohort 2: 316 µg

Cohort 3: 1000µg

Arm Description

Subjects will receive 100µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.

Subjects will receive 316 µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.

Subjects will receive 1000 µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.

Outcomes

Primary Outcome Measures

Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes a general assessment.
Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes a blood test.
Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes urinalysis.
Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes chest x-ray.
Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes ophthalmology exam.
Safety of dAd5GNE vaccine
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes EKG.

Secondary Outcome Measures

Urine cocaine metabolites
Urine will be tested for benzoylecgonine (BE). The accepted value for a positive urine cocaine is urine BE of ≥ 300 ng/mL.
Anti-cocaine antibody levels over time
The primary endpoint is average cocaine titers (week 10 - week 22) > 4.0 x 105 titer units.

Full Information

First Posted
May 19, 2015
Last Updated
January 30, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT02455479
Brief Title
Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals
Official Title
Phase I Randomized, Double-blind, Placebo Control Study for an Anti-cocaine Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 26, 2012 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
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
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the safety and preliminary efficacy of an anti-cocaine vaccine called dAd5GNE in cocaine-dependent individuals. It uses the concept of a vaccine to treat the neurological effects of cocaine by evoking "immunity" to prevent the effects of cocaine on the brain.
Detailed Description
This is a Phase I dose-ranging, placebo-controlled, double blind study assessing the safety and preliminary efficacy of an anti-cocaine vaccine called "dAd5GNE vaccine". The vaccine is designed to prevent cocaine from reaching the brain. The vaccine is comprised of GNE, a cocaine-like molecule that is linked to the capsid protein of a disrupted serotype 5 adenovirus. The vaccine is used to evoke "immunity" to prevent cocaine from reaching the brain. The vaccine evokes an immune system response and stimulates the creation of anti-cocaine antibodies. The antibodies bind to the cocaine molecules when a person takes cocaine and prevents the cocaine molecules from reaching the brain. This cocaine-antibody complex is not able to cross the blood brain barrier and thus eliminates the effects of cocaine on the brain, as seen in pre-clinical studies done by our group. In mice, rats and nonhuman primates, this vaccine evoked a persistent, high titer, high affinity IgG anti-cocaine antibody response. The pre-clinical studies conducted establish efficacy for high anti-cocaine antibody titers. The immunity sequesters parenterally administered cocaine in the blood, in mice, rats and nonhuman primates (Appendix I-III). For each subject, the study will take place over a period of 32 weeks from the time of the first vaccine administration, and will enroll cocaine addicts, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revisions (DSM-V-TR).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Dependence
Keywords
cocaine vaccine, cocaine dependence, Cocaine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: 100µg
Arm Type
Other
Arm Description
Subjects will receive 100µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.
Arm Title
Cohort 2: 316 µg
Arm Type
Other
Arm Description
Subjects will receive 316 µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.
Arm Title
Cohort 3: 1000µg
Arm Type
Other
Arm Description
Subjects will receive 1000 µg dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16 and 20.
Intervention Type
Biological
Intervention Name(s)
dAd5GNE Vaccine
Intervention Description
dAd5GNE Vaccine or Placebo dAd5GNE Vaccine
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
dAd5GNE Vaccine or Placebo dAd5GNE Vaccine
Primary Outcome Measure Information:
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes a general assessment.
Time Frame
32 weeks
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes a blood test.
Time Frame
32 weeks
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes urinalysis.
Time Frame
32 weeks
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes chest x-ray.
Time Frame
32 weeks
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes ophthalmology exam.
Time Frame
32 weeks
Title
Safety of dAd5GNE vaccine
Description
The primary endpoint is to establish the safety of dAd5GNE vaccine using general safety parameters, which includes EKG.
Time Frame
32 weeks
Secondary Outcome Measure Information:
Title
Urine cocaine metabolites
Description
Urine will be tested for benzoylecgonine (BE). The accepted value for a positive urine cocaine is urine BE of ≥ 300 ng/mL.
Time Frame
32 weeks
Title
Anti-cocaine antibody levels over time
Description
The primary endpoint is average cocaine titers (week 10 - week 22) > 4.0 x 105 titer units.
Time Frame
32 weeks
Other Pre-specified Outcome Measures:
Title
For Information Only
Description
Anti-cocaine antibody subtypes, affinity, and specificity
Time Frame
32 weeks
Title
For Information Only
Description
Anti-Ad5 antibodies
Time Frame
32 weeks
Title
For Information Only
Description
Cocaine craving self-report
Time Frame
32 weeks
Title
For Information Only
Description
Timeline followback (TLFB) drug use calendar
Time Frame
32 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Accrual will be random, with no bias as to gender or racial/ethnic group. Because the accrual process will be random, it is possible that there may be differences in the proportion of males and females, and racial/ethnic groups among the study individuals. All subjects will be concurrently participating in behavioral therapy programs run by Dr. Beeder's clinical team. Each case will be reviewed with the Eligibility Committee, comprised of three investigators other than the PI, to determine eligibility. The Principal Investigator will not participate in this process. All subjects must fulfill all inclusion criteria and none of the exclusion criteria in order to participate in this study. Inclusion Criteria: All subjects should be able to provide informed consent. Must provide HIV informed consent. Males and females, 21- 69 years of age. Individuals that have been diagnosed with a cocaine use disorder according to DSM-V-TR criteria, with documented evidence of cocaine use within the past 60 days and have previously used an average of 1 to 10 grams of powdered and/or crack cocaine (via insufflation or smoking only) per week. Any prior 1 to 4 month period of cocaine abstinence in the past year will be excluded when calculating average cocaine use to evaluate study eligibility. 6. Fertile males and females must agree to use adequate forms of contraception for the duration of the entire study. 7. Body weight > 45 kg. Exclusion Criteria: Individuals not deemed in good overall health by the investigator. Diagnosed history of severe psychotic disorders. Abnormal EKG at screening with changes consistent with cardiac disease. History of significant cardiovascular disease, hypertension, prior myocardial infarction and/or cerebrovascular event. Individuals who are currently on beta-blockers. Physical signs or laboratory values suggestive of systemic disorders. History of attempted suicide, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) and/or committed homicide. History of diagnosed obsessive compulsive disorder (OCD). Known allergy to soy. Individuals who are currently taking alprazolam (Xanax) or ziprasidone (Geodon). Evidence of active infection of any types, including COVID-19, or positive for human immunodeficiency virus (HIV). Historical or current use of immunomodulators or immunosuppressants <5 years prior to screening. Receipt of blood within 3 months of screening. Females who are pregnant or nursing. Concurrent participation in any other FDA approved Investigational New Drug. Abnormal liver function (transaminases greater than 2x the upper limit of normal values) eGFR <30 mL/min/1.73 m2 Severe substance use disorder based on DSM-V-TR criteria (excluding cocaine, nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment) currently not in remission according to one of the following criteria: Early Full Remission: This specifier is used if none of the criteria for Dependence or Abuse have been met for at least 1 month, but less than 12 months OR Early Partial Remission: This specifier is used if only one or more (but not all) of the criteria for Dependence or Abuse has/have been met for at least 1 month, but less than 12 months. OR Sustained Full Remission: This specifier is used if none of the criteria for Dependence or Abuse have been met at any time during a period of 12 months or longer OR Sustained Partial Remission: This specifier is used if only one or more (but not all) of the criteria for Dependence or Abuse has/have been met for a period of 12 months or longer OR On Agonist Therapy: This specifier is used if the individual is on a prescribed agonist medication, and none of the criteria for Dependence or Abuse has been met for that class of medication for at least the past month (except tolerance to, or withdrawal from, the agonist). This category also applies to those being treated for Dependence using a partial agonist or an agonist/antagonist OR Substance Use Related Disorder (mild) up to two disorders: Patients that are assessed to have mild substance-use-related disorders according to the DSM-V criteria will be allowed to participate in the study as long as the number of the disorder-resulting substances does not exceed two (with the exception of the nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment). History of any seizure disorder. Individuals with history of Guillain-Barré Syndrome. Diagnosis of >2 Substance Use Related Disorders (mild) based on DSM-V- TR criteria (excluding nicotine, caffeine, alcohol, marijuana and opiates prescribed for medication assisted therapy or pain treatment On a prescribed agonist medication, with criteria for dependence or abuse for that class ofmedication for at least the past month (except tolerance to, or withdrawal from, the agonist
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra Hyde
Phone
646-962-2672
Email
sah2003@med.cornell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald G Crystal, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
WCMC Department of Genetic Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Hyde
Phone
646-962-2672
Email
sah2003@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Mei Wang
Email
mew2001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Ronald Crystal, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals

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