A vaccine developed at Weill Cornell Medicine and New York–Presbyterian to blunt the effects of cocaine has advanced to clinical trials. After demonstrating that the vaccine prevented cocaine from reaching the brain in animal studies, investigators are now enrolling active cocaine addicts in a phase 1 randomized controlled study to test how it works in people.
“Cocaine addiction is a huge problem that affects more than two million people in the United States, and results in more than 500,000 annual visits to emergency rooms,” said principal investigator Dr. Ronald Crystal. “While there are drugs, like methadone, designed to treat heroin, there aren’t any therapeutics available to treat cocaine addiction. We hope that our vaccine will change that.”
While most drugs that target addiction are designed to disrupt processes in the brain, the new vaccine, called dAd5GNE, is meant to absorb cocaine in the bloodstream—well before it has had a chance to pass the blood–brain barrier and produce a dopamine-induced “high.”
The dAd5GNE vaccine works by linking a cocaine-like molecule called GNE to a disrupted protein of an inactive adenovirus that typically causes cold-like symptoms and is likely to produce an immune response. The immune system then unleashes antibodies that attack both the virus and the cocaine-like molecules connected to it. Once the body sees cocaine as the enemy, if the drug enters the bloodstream, the body will respond with a flood of anticocaine antibodies, each meant to gobble up cocaine like a Pac-man, Crystal said. This means that if someone who has received the vaccine uses cocaine, within seconds it passes from the lungs to the bloodstream, and once there, the antibodies attack.
“The goal of this vaccine is to prevent cocaine from reaching the brain,” Crystal said. “While we know that this works very well in animals, now we need to find out if the vaccine will cause enough anticocaine antibodies to be produced so that it works in humans, too.”
The investigators are looking to enroll 30 subjects who are active cocaine users. The participants in the randomized, double-blind study will be divided into three consecutive, 10-person cohorts. Each cohort of 10 subjects will be randomly split into seven subjects receiving the vaccine and three subjects receiving placebo.
Before receiving the vaccine, each participant will be required to give up cocaine for at least 30 days, during which time they will undergo frequent urine screens to test for cocaine use. Their first vaccine dose will be administered as an injection in the shoulder. Additional boosters will be given every four weeks until the participant has received a total of six injections. After the final booster is given in week 20, the subjects will be monitored for another three months, until the study’s conclusion after 32 weeks.
Each participant will meet with investigators two or three times per week to assess safety and efficacy. These meetings will include regular urine drug screens, electrocardiograms, complete blood counts, and other measures of safety, as well as reviews of any anticocaine antibodies in the participants’ systems, self-reports on cocaine cravings, and the subjects’ desire for other drugs and alcohol. All of the participants will undergo standard drug-dependency therapy throughout the study.
After the first group of 10 subjects is finished, the second group will begin, followed by the third group. In total, 21 subjects will receive the vaccine in escalating doses, and nine subjects will receive placebo. The entire study is expected to take approximately three years to complete.
“Most people who become cocaine addicts want to give it up, but struggle to kick the habit in the long-term,” Crystal said. “If this vaccine works, it could represent a lifetime therapeutic for addicts.”
Source: Weill Cornell Medicine; August 8, 2016.