The first experimental vaccine to be tested in the United States for treatment of opioid use disorder is being studied in a phase 1a/1b clinical trial led by researchers at Columbia University Vagelos College of Physicians and Surgeons.
“We have good medications to treat opioid use disorder, but about half of the people who use these medications relapse after about six months,” says Sandra Comer, PhD, professor of neurobiology in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons and principal investigator of the trial. “A vaccine that lasts for several months, given in combination with any of these medications, could help many more people beat their addiction and potentially protect them from an overdose death if a patient relapses.”
The experimental vaccine—developed by Marco Pravetoni, PhD, professor of pharmacology and medicine at the University of Minnesota Medical School—is designed to prevent oxycodone from getting into the brain where it causes a euphoric feeling, or “high,” and can impair the brain’s breathing centers and cause death if a user overdoses.
Nearly 50,000 Americans died from opioid-related overdoses in 2019, and new data from the CDC suggest that drug overdose deaths surged to a record level of 87,000 in 2020 during the pandemic, driven largely by fentanyl and other synthetic opioids.
“Vaccine development has been a tremendous boone to humanity. This innovative work brings it to bear on the scourge of addiction with the hope of having a great impact”, says Jeffrey A. Lieberman, MD, the Lawrence C. Kolb Professor of Psychiatry and chair of the Department of Psychiatry department at Columbia University Vagelos College of Physicians and Surgeons.
Vaccine is designed to prevent oxycodone from getting into the brain
The vaccine is designed to generate antibodies to oxycodone, a commonly abused prescription opioid.
If an individual takes oxycodone after vaccination, the antibodies latch onto the drug and prevent it from crossing the blood-brain barrier. Since the opioid does not reach the brain, the user does not get high. The vaccine also may protect against death from overdose due to respiratory depression, which occurs when oxycodone acts centrally in the brain.
In preclinical studies, animals that received the vaccine reduced self-administration of the drug and were protected from toxicity and signs of overdose, such as respiratory depression.
Because the vaccine specifically targets oxycodone, it doesn’t interfere with other opioid-based medications to treat opioid use disorder or with naloxone, a drug used to resuscitate patients who have overdosed.
How the trial works
The trial is enrolling volunteers who are opioid users but not receiving treatment with medications to combat opioid use disorder. One group of trial volunteers will be given a placebo; two other groups will receive either a low or high dose of the active vaccine.
The primary aim of the trial is to determine if the vaccine is well-tolerated and safe, but researchers also will seek to determine if the vaccine produces sufficient antibodies and can prevent euphoria when the volunteers are given oxycodone.
The Columbia investigators have decades of experience administering opioids to people in research studies. During the vaccine trial, the volunteers will be closely monitored by a team of physicians and nurses for several weeks in an inpatient unit to look for adverse events and determine their response to oxycodone after vaccination. The researchers will then study participants’ drug use behavior on an outpatient basis. Jeanne Manubay, MD, assistant clinical professor of medicine in the Department of Psychiatry at Columbia University, will oversee patient monitoring for the trial.
As a parallel to activities at Columbia, researchers at the University of Minnesota are conducting pharmacokinetic and immunological monitoring in blood samples from participants to better understand how the vaccine works. They also hope to identify biomarkers that can predict vaccine efficacy.
The study is being piloted in up to 24 volunteers. If the vaccine proves safe and shows potential efficacy, the trial will be expanded to 45 volunteers.
The oxycodone vaccine will need to be tested in phase 2 and phase 3 trials to determine its efficacy.
Because the chemical structure of different opioids—including oxycodone, heroin, and fentanyl—vary by drug, different vaccines are needed for each opioid. The teams at Columbia and University of Minnesota are working to develop similar vaccines against heroin and fentanyl.
“Clinicians would be able to give the oxycodone vaccine to individuals who mainly use that particular drug but could also administer additional opioid vaccines for those who use other opioids or to prevent patients from switching to another opioid,” Comer says.
“A fentanyl vaccine could also be used to protect first responders, law enforcement, or soldiers if they inadvertently inhale carfentanil—which can be fatal in very small doses.”
Sandra Comer, PhD, is also a research scientist at New York State Psychiatric Institute.
Volunteers are also being enrolled by Clinilabs Drug Development Corp, a contract research organization based in Eatontown, New Jersey.
To learn more about the study or review the volunteer qualifications, call 646-774-6243 or visit https://recruit.cumc.columbia.edu/clinical_trial/2168.
The trial is funded by a grant from the National Institutes of Health (3UG3DA047711 and 3UG3DA047711-02S1).