Clinical Trials of Multivalent Opioid Vaccine Components

• ClinicalTrials.gov Identifier: NCT04458545
• Recruitment Status: Recruiting
• First Posted: July 7, 2020
• Last Update Posted: January 31, 2024
• Sponsor: New York State Psychiatric Institute
• Collaborator: Clinilabs, Inc.
• Information provided by (Responsible Party): Sandra D. Comer, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: June 16, 2020
• First Posted Date: July 7, 2020
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: October 8, 2020
• Estimated Primary Completion Date: December 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2020)

• Incidence of Treatment-Emergent Adverse Events [ Time Frame: Beginning from first vaccination through study completion (43 Weeks). ]
  Safety and tolerability of the opioid vaccine.
• Effects of Vaccine on Intranasal Drug Positive Subjective Effects [ Time Frame: Throughout the testing session [i.e., pre-dose baseline (Time 0)- Thru- 4.5 hours post-dose]. ]
  Peak self-reported drug "Liking." Measured using a visual analog scale (0-100).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trials of Multivalent Opioid Vaccine Components
• Official Title: Phase 1A/1B Clinical Trials of Multivalent Opioid Vaccine Components
• Brief Summary: 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.

Detailed Description

Overview: The proposed study is designed as a Phase 1a/1b clinical trial of an oxycodone vaccine (Oxy(Gly)4-sKLH Conjugate Vaccine, Adsorbed). Healthy adults, aged 18 to 59 years, who meet DSM-5 criteria for OUD but are not seeking treatment for their drug use, and are physically dependent on opioids will be recruited. This study will employ a between-groups, placebo-controlled design (two active vaccine doses, 1 placebo).

Immunization will occur at Weeks 0, 3, 6 and 18. The Oxy(Gly)4-sKLH vaccine adsorbed to aluminum adjuvant (Alhydrogel®) or aluminum adjuvant as placebo, will be injected intramuscularly (IM) into the deltoid muscle. Each subject completing the study will participate for 43 weeks including: One Screening Phase (Weeks -6 to -2), two Inpatient Phases (Weeks -2-8 and 18-20), two Outpatient Phases (Weeks 8-18, 20-21), and a Follow Up Phase (Week 21, 23, 30, 34, 38, and 42 (1-week, 1-month, 3-month, 4-month, 5-month, and 6-month follow up). Subjects will be immunized during Weeks 0, 3, 6 and 18 with either Oxy(Gly)4-sKLH (either 100 μg or 400 μg dose; different dose levels will be administered by varying the volume of the 400 μg/mL formulation) adsorbed on aluminum adjuvant or aluminum alone as placebo.

Screening Phase (Weeks -6 thru -2): Eligibility for admission into the study will be based on a psychiatric evaluation, physical examination, blood and urine testing, electrocardiogram, drug history assessment, urine drug testing, and ascertainment of physical dependence on opioids via naloxone challenge and/or objective confirmation of opioid withdrawal signs/symptoms

Inpatient Phases (Weeks -1-8 & 18-19) Opioid Maintenance and Testing Sessions: During the inpatient phases participants will be maintained on oral morphine 120 mg/day. During testing sessions, intranasal oxycodone (0, 25, 50, and 100 mg/70kg) will be administered during each inpatient phase to assess the ability of the vaccine to reduce positive subjective ratings (e.g., Drug Liking, High, etc.). Intranasal heroin (100 mg/70 kg) and lactose powder (placebo) will be used as positive and negative controls, respectively. In addition to assessing subjective effects, vital signs and other physiological measures are collected throughout the testing period (4.5 hours). The order ofthe different doses will be randomized and one dose of either oxycodone, heroin, or placebo will be given each day on 5 consecutive days. During testing sessions a physician or nurse practitioner will be on the floor for the first hour after IN dosing, and on-call throughout the session.

Outpatient Phases (Weeks 9-17, 20-21): Participants will return to the laboratory weekly during the outpatient phases in order to assess titer levels, maintain good contact and to assess drug use, adverse events, and concomitant medication use. Blood tests (hematology, chemistry) and urinalysis will be performed repeatedly throughout the study: just prior to each inpatient phase and during the follow up visits at the end of the study (Weeks 8, 12, 17, 21, 23, and 30). In addition, the following assessments will be completed weekly throughout the study: Physical exam, 12-lead ECG, body weight, vital signs, and standard assessments of depression and suicidal thoughts/behaviors, along with cognitive functioning. The Columbia Suicide Severity Rating Scale (CSSRS) and clinical interviews will be used to provide ongoing assessments of this risk throughout the inpatient and outpatient phases of the study.

Discharge (Week 19) and Follow-Up (Weeks 21, 23, 30, 34, 38, and 42): During the last week of the study and/or prior to each inpatient discharge, participants will receive counseling about different treatment options for opioid use disorder. For those participants requesting treatment, appropriate arrangements will be made.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants are randomized among three arms i.e., to one of three doses of the opioid vaccine: Placebo, Low and High dose. Under each vaccine condition, the participant is administered 5 intranasal drugs.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Opioid-use Disorder

Intervention

• Drug: Placebo
  Intranasal placebo 0mg
• Drug: Oxy 25 mg
  Intranasal oxycodone 25mg
• Drug: OXY 50 mg
  Intranasal oxycodone 50mg
• Drug: OXY 100 mg
  Intranasal oxycodone 100mg
• Drug: Heroin
  Intranasal heroin 100mg

Study Arms

• Placebo Comparator: Placebo Vaccine
  Interventions:

  • Drug: Placebo
  • Drug: Oxy 25 mg
  • Drug: OXY 50 mg
  • Drug: OXY 100 mg
  • Drug: Heroin
• Experimental: Low Dose Vaccine (100 μg)
  Interventions:

  • Drug: Placebo
  • Drug: Oxy 25 mg
  • Drug: OXY 50 mg
  • Drug: OXY 100 mg
  • Drug: Heroin
• Experimental: High Dose Vaccine (400 μg)
  Interventions:

  • Drug: Placebo
  • Drug: Oxy 25 mg
  • Drug: OXY 50 mg
  • Drug: OXY 100 mg
  • Drug: Heroin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 30, 2020): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2025
• Estimated Primary Completion Date: December 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

All participants in Group 1 must meet all of the following Inclusion Criteria to be enrolled:

• Evidence of personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Male or female aged 18 to 59 years.
• Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e., sterilized via hysterectomy or bilateral tubal ligation or at least 1 years post-menopausal) or of childbearing potential but practicing a medically acceptable method of birth control.
• Meets current DSM 5 criteria for moderate-severe OUD, physical dependence on opioids, and current use of opioids will be in amounts and/or frequencies that meet or exceed those used in the study (3-4 tablets of a prescription opioid medication per day or 1-2 bags of heroin and/or fentanyl per day). Participants may meet criteria for other behavioral disorders (e.g. gambling) or substance use disorders (cocaine or marijuana), but cannot be physically dependent on drugs that pose risk of withdrawal that requires medical management such as alcohol or benzodiazepines. Participant must self-identify their opioid of choice as being other than oxycodone, oxymorphone, hydrocodone, and hydromorphone (e.g., a heroin and/or fentanyl user). In addition, we will only include individuals who have prior experience with intranasal opioid use. Only participants with a minimum use of 1-2 bags of heroin and/or fentanyl per day and a maximum of 20 bags of heroin/fentanyl per day will be enrolled.

The lower limit ensures that participants are physically dependent on opioids and are able to tolerate the proposed dosing. The upper limit is consistent with our current experience in recruiting this population (where use of 30-50 bags/day is commonly reported because of the shorter duration of psychoactive effects produced by fentanyl compared to heroin).

• Not currently seeking treatment for drug use as defined by urine samples positive for illicit opioids, and at least 2 urine samples negative for buprenorphine and methadone, spaced at least 3 days apart, prior to enrollment.
• Willing and able to comply with scheduled visits, dosing plan, laboratory tests, and other study procedures.
• Patients who weigh less than 300 pounds and/or have less than a maximum girth of 52 inches.

A participant will not be enrolled in Group 1 if he/she meets any of the following Exclusion Criteria:

• Participation in a clinical trial and receipt of investigational drug(s) during 30 days (or 5 half-lives, whichever is longer) prior to randomization.
• Sensitivity, allergy, or contraindication to opioids, alum, or any components of the vaccine.
• Prior exposure to opioid vaccines or vaccines containing KLH.
• Use of prescription psychotropic medications that would potentially interfere with study procedures.
• Women of childbearing age who are pregnant, lactating or, not practicing or willing to begin a medically acceptable method of birth control.
• Cannot read or understand the self-report assessment forms unaided or are so severely disabled that they cannot comply with the requirements of the study.

• Medical conditions that may make study participation hazardous:

  • History of seizures or cardiac risk conditions (unstable angina, cardiac arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling that the heart is beating too hard, too fast, skipping a beat, or fluttering).
  • Elevated liver function tests (i.e., AST and ALT > 2 times the upper limit of normal).
  • Impaired renal function (creatinine > 1.2).
  • Hypertension (>140/90).
  • Asthmatic symptoms within the past 3 years.
  • Active hepatitis [e.g. symptomatic with a positive test for hepatitis B (HBsAg), hepatitis C antibody (HCV), HIV1/HIV2 antibody/antigen].
  • Significant hepatocellular injury as evidenced by elevated bilirubin levels (>1.3), or elevated levels (over 3x the upper limit of normal) of aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT).
  • Creatinine clearance estimated to be less than 60 ml/min.
  • Current gastric disease such as peptic ulcer disease, gastritis, upper gastrointestinal bleeding, or any gastrointestinal malignancy or precancerous condition.
  • Sleep apnea as assessed by the STOP-Bang questionnaire; those with high risk will be excluded from the study
  • Hemoglobin: Women <11.5; men <13
• Newly diagnosed HIV infection or known HIV infection with CD4 counts below normal levels, active tuberculosis, or other immunocompromising diseases.
• Current chronic pain (persistent for longer than 3 months).
• Current or history of psychotic disorder or other severe Axis I disorder based on DSM 5 criteria, other than OUD, including physical dependence on drugs that pose risk of withdrawal that requires medical management such as alcohol or benzodiazepines. Participants diagnosed with dysthymia or mild-moderate depression with no recent suicidal ideation may be included. Recent suicidal ideation" is defined as thoughts about suicide within the past month.
• Previous serious or unexpected adverse reaction to a vaccine, including Guillain-Barré syndrome.
• Use of inhaled corticosteroids, immunosuppressive agents or other medications within 30 days prior to administration of investigational product that might interfere with an immune response. Antihistamines may not be used within 7 days prior to administration of investigational product.
• Use of any vaccine, with the exception of influenza vaccine, or COVID-19 vaccine 30 days prior to administration of study product. Participants who have received the Moderna or Pfizer COVID-19 vaccine will not be eligible to receive study product until 30 days after they have received the second vaccine dose; participants who have received the Johnson and Johnson COVID-19 vaccine will not be eligible to receive study product until 30 days after they have received the vaccine dose. Known history of cancer or cancer treatment within 12 months prior to administration of investigational product.
• Known history of cancer or cancer treatment within 12 months prior to administration of investigational product.
• Receipt of blood products within 3 months of screening.
• Anticipated inability to fulfill all visits and examination procedures throughout the study period
• Individuals who are on medication-assisted treatment for Opioid Use Disorder (e.g., buprenorphine, buprenorphine/naloxone, methadone, naltrexone). We will also exclude participants from our study who "doctor shop" by reviewing information obtained from PMPs.
• Individuals who currently (within the past 3 months) have a temporary restraining order (TRO) against them or against another person.
• Lactose Allergy: Lactose is used as an excipient in the compounded challenge test articles.
• History of prior opiate overdose (within the past 2 years) identified by self-report during multiple interviews conducted during the screening process.

All participants in Group 2 must meet all of the following Inclusion Criteria to be enrolled:

• Evidence of personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Male or female aged 18 to 59 years.
• Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e., sterilized via hysterectomy or bilateral tubal ligation or at least 1 years post-menopausal) or of childbearing potential but practicing a medically acceptable method of birth control.
• Meets current DSM 5 criteria for moderate-severe OUD, physical dependence on opioids in the past year [GROUP 2 ONLY: Participants must be engaged in treatment with buprenorphine, methadone or extended-release naltrexone for at least 8 weeks prior to enrollment.] Participants may meet criteria for other behavioral disorders (e.g. gambling) or substance use disorders (cocaine or marijuana), but cannot have severe co-occurring substance use disorders (e.g., sedative use disorder, alcohol use disorder) that are deemed likely to interfere with study procedures, based on clinical judgement. Not currently seeking treatment for drug use as defined by urine samples positive for illicit opioids, and at least 2 urine samples negative for buprenorphine and methadone, spaced at least 3 days apart, prior to enrollment.
• Participants who are actively engaged in treatment for OUD will only be eligible for Group 2. These participants must be engaged in treatment for at least 8 weeks prior to study enrollment. Engagement in treatment will be assessed based on self-report, collateral information from treatment provider and by urine samples consistently positive for buprenorphine and/or methadone.
• Willing and able to comply with scheduled visits, dosing plan, laboratory tests, and other study procedures.
• Patients who weigh less than 300 pounds and/or have less than a maximum girth of 52 inches.

A participant will not be enrolled in Group 2 if he/she meets any of the following Exclusion Criteria:

• Participation in a clinical trial and receipt of investigational drug(s) during 30 days (or 5 half-lives, whichever is longer) prior to randomization.
• Sensitivity, allergy, or contraindication to opioids, alum, or any components of the vaccine.
• Prior exposure to opioid vaccines or vaccines containing KLH.
• Use of prescription psychotropic medications that would potentially interfere with study procedures.
• Women of childbearing age who are pregnant, lactating or, not practicing or willing to begin a medically acceptable method of birth control.
• Cannot read or understand the self-report assessment forms unaided or are so severely disabled that they cannot comply with the requirements of the study.

• Medical conditions that may make study participation hazardous:

  • History of seizures or cardiac risk conditions (unstable angina, cardiac arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling that the heart is beating too hard, too fast, skipping a beat, or fluttering).
  • Elevated liver function tests (i.e., AST and ALT > 2 times the upper limit of normal).
  • Impaired renal function (creatinine > 1.2).
  • Hypertension (>140/90).
  • Asthmatic symptoms within the past 3 years.
  • Active hepatitis [e.g. symptomatic with a positive test for hepatitis B (HBsAg), hepatitis C antibody (HCV), HIV1/HIV2 antibody/antigen].
  • Significant hepatocellular injury as evidenced by elevated bilirubin levels (>1.3), or elevated levels (over 3x the upper limit of normal) of aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT).
  • Creatinine clearance estimated to be less than 60 ml/min.
  • Current gastric disease such as peptic ulcer disease, gastritis, upper gastrointestinal bleeding, or any gastrointestinal malignancy or precancerous condition.
  • Sleep apnea as assessed by the STOP-Bang questionnaire; those with high risk will be excluded from the study
  • Hemoglobin: Women <10.5; men <11.5
• Newly diagnosed HIV infection or known HIV infection with CD4 counts below normal levels, active tuberculosis, or other immunocompromising diseases.
• Current or history of psychotic disorder or other severe Axis I disorder based on DSM 5 criteria, other than OUD that are deemed by PIs, MD or NP likely to interfere with study procedures. Participants diagnosed with dysthymia or mild-moderate depression with no recent suicidal ideation may be included. "Recent suicidal ideation" is defined as thoughts about suicide within the past month.
• Previous serious or unexpected adverse reaction to a vaccine, including Guillain-Barré syndrome.
• Use of inhaled corticosteroids, immunosuppressive agents or other medications within 30 days prior to administration of investigational product that might interfere with an immune response. Antihistamines may not be used within 7 days prior to administration of investigational product.
• Use of any vaccine, with the exception of influenza vaccine, or COVID-19 vaccine 30 days prior to administration of study product. Participants who have received the Moderna or Pfizer COVID-19 vaccine will not be eligible to receive study product until 30 days after they have received the second vaccine dose; participants who have received the Johnson and Johnson COVID-19 vaccine will not be eligible to receive study product until 30 days after they have received the vaccine dose. Known history of cancer or cancer treatment within 12 months prior to administration of investigational product.
• Known history of cancer or cancer treatment within 12 months prior to administration of investigational product.
• Receipt of blood products within 3 months of screening.
• Anticipated inability to fulfill all visits and examination procedures throughout the study period
• Individuals who currently (within the past 3 months) have a temporary restraining order (TRO) against them or against another person.
• History of prior opiate overdose (within the past 2 years) identified by self-report during multiple interviews conducted during the screening process.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jermaine Jones, PhD; 16467746113; jermaine.jones@nyspi.columbia.edu

Contact: Rachel Luba, PhD; Rachel.Luba@nyspi.columbia.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04458545
• Other Study ID Numbers: 7712
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sandra D. Comer, New York State Psychiatric Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: New York State Psychiatric Institute
• Original Study Sponsor: Same as current
• Collaborators: Clinilabs, Inc.

Investigators

• Principal Investigator: Sandra D Comer, PhD; New York State Psychiatric Institute

• PRS Account: New York State Psychiatric Institute
• Verification Date: January 2024