Cocaine Vaccine for Cocaine Addiction

Overseen By Sandra Hyde

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Beta-blockers, Xanax, Geodon, Immunosuppressants

Disqualifiers: Severe psychotic disorders, Cardiovascular disease, OCD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 20 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental vaccine, dAd5GNE (also known as the Anti-Cocaine Vaccine), to determine if it can help people with cocaine addiction by creating a kind of "immunity" that blocks cocaine's effects on the brain. In its early stages, the trial primarily aims to assess the vaccine's safety and potential to reduce cocaine use. Participants will receive different doses of the vaccine or a placebo over several months. Ideal candidates are individuals diagnosed with a cocaine use disorder who have used cocaine recently. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as beta-blockers, alprazolam (Xanax), and ziprasidone (Geodon). If you are on these medications, you would need to discontinue them to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the dAd5GNE vaccine has been tested previously and is considered safe at a low dose. In earlier studies, recipients developed antibodies that specifically target cocaine. These antibodies help lower cocaine levels in the brain, suggesting the vaccine can work without causing harmful effects.

Evidence indicates that participants who received the vaccine were more likely to test negative for cocaine. The vaccine also appears to reduce the usual hyperactive effects of cocaine. This suggests the vaccine not only aims to treat addiction but does so with minimal risk to participants.

While these findings are promising, it is important to remember that this trial is in an early phase, primarily focusing on safety. The vaccine's tolerability is being closely monitored to ensure it is safe for further testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cocaine addiction focus on behavioral therapy or medications to manage withdrawal symptoms and cravings, but they don't directly target cocaine itself. The dAd5GNE vaccine is unique because it aims to create antibodies that bind to cocaine molecules in the bloodstream, preventing them from reaching the brain and triggering a high. This mechanism is groundbreaking because it acts as a sort of "shield" against cocaine, potentially reducing the incentive to use the drug. Researchers are excited about this vaccine because it offers a novel approach to addiction treatment by directly targeting the drug rather than just the symptoms of addiction.

What evidence suggests that the dAd5GNE vaccine might be an effective treatment for cocaine addiction?

Research shows that the dAd5GNE vaccine might help treat cocaine addiction by stopping cocaine from affecting the brain. Studies have found that the vaccine lowers cocaine levels in the brain and reduces the increased movement and energy caused by the drug. In this trial, participants will receive different dosages of the dAd5GNE vaccine or a placebo. In a small trial, those who received the vaccine were more likely to test negative for cocaine use. This suggests that the vaccine may help lessen cocaine's effects and potentially reduce addiction. The vaccine acts like a blocker, preventing cocaine from entering the brain and decreasing its stimulating effects. ^{1 2 4 6 7}

Who Is on the Research Team?

Ronald G Crystal, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults aged 21-69 with cocaine use disorder, using 1-10 grams of cocaine weekly. They must be in good health, not have severe mental disorders or significant heart disease, and cannot be on certain medications like beta-blockers or immunosuppressants. Participants should agree to contraception and will also receive behavioral therapy.

Inclusion Criteria

The study will randomly accept participants without any preference for gender or ethnicity. Your participation in the study will not be affected by your gender or ethnicity. All participants will also be receiving behavioral therapy from Dr. Beeder's team. An Eligibility Committee, made up of three investigators other than the main researcher, will review each participant's case to decide if they are eligible to join the study. The main researcher will not be involved in this decision-making process.

Must provide HIV informed consent.

My body weight is over 45 kg.

Exclusion Criteria

- 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.

Known allergy to soy.

Concurrent participation in any other FDA approved Investigational New Drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the dAd5GNE vaccine or placebo at weeks 0, 4, 8, 12, 16, and 20

20 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• dAd5GNE Vaccine

Trial Overview The study tests the safety and initial effectiveness of a new anti-cocaine vaccine called dAd5GNE. It aims to create 'immunity' against the neurological effects of cocaine. Participants are randomly assigned to receive either the vaccine or a placebo while undergoing behavioral therapy.

How Is the Trial Designed?

Group I: Cohort 3: 1000µg Experimental Treatment 2 Interventions

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

Group II: Cohort 2: 316 µg Experimental Treatment 2 Interventions

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

Group III: Cohort 1: 100µg Experimental Treatment 2 Interventions

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

dAd5GNE Vaccine is already approved in United States for the following indications:

Approved in United States as dAd5GNE Vaccine for:

• Cocaine dependence

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The dAd5GNE cocaine vaccine was tested in a study with 6 adult female rhesus monkeys, showing that it can significantly delay the reacquisition of cocaine self-administration after a period of abstinence, indicating its potential as a relapse prevention strategy.

While the vaccine did not significantly reduce the overall preference for cocaine over candy in most monkeys, it maintained high serum antibody levels and demonstrated a longer time to resume cocaine use in vaccinated monkeys compared to controls, suggesting a protective effect against relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of an adenovirus-based anti-cocaine vaccine to reduce cocaine self-administration and reacqusition using a choice procedure in rhesus macaques. Evans, SM., Foltin, RW., Hicks, MJ., et al.[2018]

The dAd5GNE cocaine vaccine produced long-lasting high levels of anti-cocaine antibodies in rats, effectively reducing cocaine-related behaviors such as hyperlocomotion and self-administration.

Vaccinated rats showed significantly less motivation to seek cocaine and did not exhibit typical relapse behaviors when primed with cocaine, indicating the vaccine's potential to block cocaine-seeking behavior and treat addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. Wee, S., Hicks, MJ., De, BP., et al.[2021]

The anticocaine vaccine dAd5GNE effectively prevents cocaine from reaching the brain and other sensitive organs by sequestering it in the blood, which could help treat cocaine use disorders.

In studies with nonhuman primates, the vaccine did not show any adverse effects on major organs, indicating a favorable safety profile while limiting cocaine's systemic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fate of systemically administered cocaine in nonhuman primates treated with the dAd5GNE anticocaine vaccine. Hicks, MJ., Kaminsky, SM., De, BP., et al.[2021]

Cocaine addiction is a significant issue, leading to criminal activities, and currently, there are no effective medications to treat it, highlighting the need for innovative solutions.

Vaccines against cocaine are being developed, with one already in clinical trials, showing promise as a potential method to help motivated addicts overcome their addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cocaine vaccine development. Kinsey, BM., Kosten, TR., Orson, FM.[2021]

The cocaine vaccine dAd5GNE successfully induced high levels of anti-cocaine antibodies in nonhuman primates, which significantly reduced cocaine's ability to bind to the dopamine transporter (DAT) in the brain.

When anti-cocaine antibody levels were above 4 × 10(5), cocaine occupancy at DAT dropped to less than 20%, well below the threshold needed to produce a 'high', suggesting the vaccine could effectively prevent the effects of cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter. Maoz, A., Hicks, MJ., Vallabhjosula, S., et al.[2021]

The dAd5GNE cocaine vaccine effectively prevents cocaine from entering the central nervous system in models of both daily and binge cocaine use, demonstrating its potential to reduce cocaine-induced hyperactivity and seizures.

A clinical trial has been initiated to further evaluate the safety and efficacy of dAd5GNE in humans, with the expectation that it will help cocaine addicts by blocking the drug's effects even during high-dose use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine vaccine dAd5GNE protects against moderate daily and high-dose "binge" cocaine use. Havlicek, DF., Rosenberg, JB., De, BP., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7703925/

Cocaine vaccine dAd5GNE protects against moderate daily ... Previous studies have shown that dAd5GNE vaccination reduces cocaine levels in the brain [10, 11] and reduces cocaine-induced hyperactivity [7] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02455479

NCT02455479 | Safety Study of a Disrupted Adenovirus ... The purpose of this study is to assess the safety and preliminary efficacy of an anti-cocaine vaccine called dAd5GNE in cocaine-dependent individuals.

3. geneticmedicine.weill.cornell.edu geneticmedicine.weill.cornell.edu/news/vaccine-may-treat-cocaine-addiction-blocking-drugs-entry-brain

Vaccine may treat cocaine addiction by blocking drug's entry ... A small trial of the vaccine, known as dAd5GNE, found that participants receiving it had a higher likelihood of testing negative for cocaine and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091305716301617

Efficacy of an adenovirus-based anti-cocaine vaccine to ... dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. ... dAd5GNE vaccine may be effective for cocaine ...

5. nature.com nature.com/articles/npp2011200

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus ... These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction.

6. reporter.nih.gov reporter.nih.gov/project-details/9853773

Clinical Assessment of Anti-cocaine Vaccine dAdGNE ... The data from this cohort demonstrated that at this low dose, the dAd5GNE vaccine is safe and elicits persistent serum cocaine-specific antibodies in the range ...

7. nature.com nature.com/articles/npp2013114

Adenovirus Capsid-Based Anti-Cocaine Vaccine Prevents ... In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 105, the cocaine occupancy ...