Opioid Vaccine for Opioid Use Disorder

Recruiting at 1 trial location

Overseen By Sandra Comer, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Psychotropics, Inhaled corticosteroids

Disqualifiers: Seizures, Cardiac conditions, Hypertension, others

Compensation: Varies

Number of Visits: 13

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Currently, abuse of prescription opioid analgesics and heroin is a serious problem in the U.S. Although several medications, including methadone, buprenorphine, and naltrexone, are available and effective in treating opioid use disorder (OUD), long-term relapse rates remain high. The current study is designed to examine a new approach to treating OUD, namely use of a vaccine targeted against oxycodone \[Oxy(Gly)4-sKLH\], one of the most commonly abused prescription opioids. The vaccination approach to treating substance use disorders relies on the ability of the vaccine to produce antibodies that bind the target drug in blood and reduce its ability to enter the brain. The long-term goal of this research will be to develop a combined vaccine against oxycodone and heroin. However, in this trial the Oxy(Gly)4-sKLH vaccine will be studied separately. This is a multi-site study, being conducted at the New York State Psychiatric Institute and the Clinilabs clinical research unit (CRU) in Eatontown, New Jersey. The current study proposes to evaluate safety (Aim 1), degree of antibody production (Aim 2), and efficacy (i.e., ability to reduced drug liking following opioid administration) (Aim 3). The oxycodone vaccine (Oxy(Gly)4-sKLH) will be tested in participants with OUD (target # completers = 45 across two study sites). This study will provide a great deal of information about the safety and potential effectiveness of the Oxy(Gly)4-sKLH vaccine in reducing the abuse of opioids. The NYSPI site is currently paused and has been paused since an institutional pause on human subjects research began in June 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.

Will I have to stop taking my current medications?

The trial requires that participants are not on medication-assisted treatment for Opioid Use Disorder, such as buprenorphine, methadone, or naltrexone. Additionally, participants cannot use certain medications like inhaled corticosteroids or immunosuppressive agents within 30 days before the study product is given.

What data supports the effectiveness of the treatment Oxy(Gly)4-sKLH for opioid use disorder?

Research shows that the Oxy(Gly)4-sKLH vaccine generates specific antibodies that reduce the effects of oxycodone, a commonly abused opioid, in animal studies. The vaccine was effective in decreasing oxycodone's impact on the brain and reducing its addictive properties, while being safe and well-tolerated in pre-clinical trials. ^{1 2 3 4 5}

Is the opioid vaccine safe for humans?

The opioid vaccine, tested under names like Oxy(Gly)4-sKLH, has shown no harmful side effects in animal studies, suggesting it is generally safe. It was well tolerated in rats, with no negative effects on blood, organs, or overall health observed. ^{1 2 3 4 6}

How is the Oxy(Gly)4-sKLH treatment different from other treatments for opioid use disorder?

The Oxy(Gly)4-sKLH treatment is unique because it is a vaccine that generates antibodies specifically targeting oxycodone, reducing its effects and distribution to the brain, unlike traditional treatments that often involve opioid substitutes or antagonists. This vaccine approach offers long-lasting protection and does not interfere with medications used to reverse overdoses. ^{1 2 3 4 5}

Research Team

Sandra D Comer, PhD

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

This trial is for adults aged 18-59 with moderate to severe opioid use disorder who are not seeking treatment and prefer drugs other than certain prescription opioids. They must be able to follow the study plan, weigh less than 300 pounds, have no major health issues like kidney problems or high blood pressure, and women must use birth control if of childbearing potential.

Inclusion Criteria

I weigh less than 300 pounds and my waist is less than 52 inches.

Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

Willing and able to comply with scheduled visits, dosing plan, laboratory tests, and other study procedures

Exclusion Criteria

I am allergic to opioids, alum, or vaccine ingredients.

I have not had cancer or cancer treatment in the last year.

I am not allergic to lactose.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Outpatient Study Visit

Participants receive the Oxy(Gly)4-sKLH vaccine or placebo at Weeks 0, 3, 6, and 18

21 weeks

4 visits (in-person)

Laboratory Session

Participants undergo laboratory assessments to evaluate immune response and drug effects

1 week

3 visits (in-person)

Extended Follow-up

Participants are monitored for safety and effectiveness after treatment

21 weeks

5 visits (in-person)

Treatment Details

Interventions

• Oxy(Gly)4-sKLH

Trial Overview The trial tests a vaccine aimed at treating opioid addiction by generating antibodies against oxycodone. It will assess safety, antibody production, and effectiveness in reducing drug liking after opioid administration. Participants will receive different doses of the vaccine or placebo across two sites.

Participant Groups

Group I: Active Vaccine (high dose or low dose) Experimental Treatment 2 Interventions

Active Oxy(Gly)4-sKLH vaccine dose (low dose or high dose)

Group II: Placebo Oxy(Gly)4-sKLH vaccine dose Placebo Group 1 Intervention

Placebo Oxy(Gly)4-sKLH vaccine

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Clinilabs, Inc.

Collaborator

Trials

9

Recruited

650+

Findings from Research

The Oxy(Gly)4-sKLH Conjugate Vaccine demonstrated strong immunogenicity, producing high antibody levels in Sprague Dawley rats even at low doses, indicating its potential effectiveness in treating opioid use disorders.

Safety assessments showed no significant toxicological effects related to the vaccine, suggesting it is well tolerated and does not cause harmful side effects, which is crucial for its future clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical safety and toxicology profile of a candidate vaccine to treat oxycodone use disorder. Hamid, FA., Marker, CL., Raleigh, MD., et al.[2023]

The OXY-dKLH vaccine effectively protects against the toxic effects of oxycodone, as evidenced by a rightward shift in dose-response curves for pain relief and respiratory depression in vaccinated rats, indicating reduced sensitivity to oxycodone's harmful effects.

Importantly, the vaccine does not interfere with the effectiveness of naloxone, an opioid antagonist used for overdose reversal, and maintains immunogenicity even when administered alongside opioids like morphine, suggesting it could be a safe option for treating oxycodone abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse. Raleigh, MD., Peterson, SJ., Laudenbach, M., et al.[2020]

The heroin vaccine (M-KLH) effectively increased the retention of heroin and its metabolites in the bloodstream while reducing their distribution to the brain, particularly at lower doses, and also protected against respiratory depression.

The oxycodone vaccine (OXY-KLH) significantly reduced the brain distribution of oxycodone, especially when administered subcutaneously, indicating that the effectiveness of these vaccines varies based on the dose and method of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats. Raleigh, MD., Laudenbach, M., Baruffaldi, F., et al.[2019]

The Oxy(Gly)4-sKLH vaccine shows promise as a therapeutic option for opioid use disorders, demonstrating sustained antibody responses for up to five months without boosting antibody levels in response to oxycodone exposure, which minimizes concerns about immune-related side effects.

This vaccine effectively reduces the reinforcing effects of oxycodone while preserving the efficacy of other opioid medications like naloxone and methadone, indicating its potential for safe integration into existing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological mechanisms underlying the efficacy of antibodies generated by a vaccine to treat oxycodone use disorder. Raleigh, MD., King, SJ., Baruffaldi, F., et al.[2022]

The study developed an opioid conjugate vaccine using OXY(Gly)(4) that produced high levels of antibodies specifically targeting oxycodone and its metabolite, oxymorphone, while showing minimal cross-reactivity with other opioids, indicating a focused immune response.

Immunization with the OXY(Gly)(4)-KLH vaccine significantly altered the pharmacokinetics of oxycodone in rats, reducing its free concentration in plasma and brain distribution, which suggests potential for this vaccine to mitigate the effects of oxycodone abuse and addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oxycodone conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia. Pravetoni, M., Le Naour, M., Harmon, TM., et al.[2021]

The study identified an effective opioid conjugate vaccine using an oxycodone-based hapten that significantly reduced the distribution of oxycodone to the brain in mice, demonstrating its potential as a treatment for opioid use disorders.

Both heroin vaccines formulated with different carrier proteins (EcoCRM and KLH) were equally effective in reducing the effects of heroin and its metabolites, suggesting promising candidates for further development in preventing opioid overdoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Characterization of Candidate Vaccines for Treatment of Opioid Use Disorders Using Clinically Viable Carrier Proteins. Baruffaldi, F., Kelcher, AH., Laudenbach, M., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pre-clinical safety and toxicology profile of a candidate vaccine to treat oxycodone use disorder. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacological mechanisms underlying the efficacy of antibodies generated by a vaccine to treat oxycodone use disorder. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

An oxycodone conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Characterization of Candidate Vaccines for Treatment of Opioid Use Disorders Using Clinically Viable Carrier Proteins. [2020]