<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04458545</url>
  </required_header>
  <id_info>
    <org_study_id>7712</org_study_id>
    <nct_id>NCT04458545</nct_id>
  </id_info>
  <brief_title>Clinical Trials of Multivalent Opioid Vaccine Components</brief_title>
  <official_title>Phase 1A/1B Clinical Trials of Multivalent Opioid Vaccine Components</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinilabs, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, abuse of prescription opioid analgesics and heroin is a serious problem in the&#xD;
      U.S. Although several medications, including methadone, buprenorphine, and naltrexone, are&#xD;
      available and effective in treating opioid use disorder (OUD), long-term relapse rates remain&#xD;
      high. The current study is designed to examine a new approach to treating OUD, namely use of&#xD;
      a vaccine targeted against oxycodone [Oxy(Gly)4-sKLH], one of the most commonly abused&#xD;
      prescription opioids. The vaccination approach to treating substance use disorders relies on&#xD;
      the ability of the vaccine to produce antibodies that bind the target drug in blood and&#xD;
      reduce its ability to enter the brain. The long-term goal of this research will be to develop&#xD;
      a combined vaccine against oxycodone and heroin. However, in this trial the Oxy(Gly)4-sKLH&#xD;
      vaccine will be studied separately. This is a multi-site study, being conducted at the New&#xD;
      York State Psychiatric Institute and the Clinilabs clinical research unit (CRU) in Eatontown,&#xD;
      New Jersey. The current study proposes to evaluate safety (Aim 1), degree of antibody&#xD;
      production (Aim 2), and efficacy (i.e., ability to reduced drug liking following opioid&#xD;
      administration) (Aim 3). The oxycodone vaccine (Oxy(Gly)4-sKLH) will be tested in&#xD;
      participants with OUD (target # completers = 45 across two study sites). This study will&#xD;
      provide a great deal of information about the safety and potential effectiveness of the&#xD;
      Oxy(Gly)4-sKLH vaccine in reducing the abuse of opioids.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overview: The proposed study is designed as a Phase 1a/1b clinical trial of an oxycodone&#xD;
      vaccine (Oxy(Gly)4-sKLH Conjugate Vaccine, Adsorbed). Healthy adults, aged 18 to 59 years,&#xD;
      who meet DSM-5 criteria for OUD but are not seeking treatment for their drug use, and are&#xD;
      physically dependent on opioids will be recruited. This study will employ a between-groups,&#xD;
      placebo-controlled design (two active vaccine doses, 1 placebo).&#xD;
&#xD;
      Immunization will occur at Weeks 0, 3, 6 and 18. The Oxy(Gly)4-sKLH vaccine adsorbed to&#xD;
      aluminum adjuvant (Alhydrogel®) or aluminum adjuvant as placebo, will be injected&#xD;
      intramuscularly (IM) into the deltoid muscle. Each subject completing the study will&#xD;
      participate for 43 weeks including: One Screening Phase (Weeks -6 to -2), two Inpatient&#xD;
      Phases (Weeks -2-8 and 18-20), two Outpatient Phases (Weeks 8-18, 20-21), and a Follow Up&#xD;
      Phase (Week 21, 23, 30, 34, 38, and 42 (1-week, 1-month, 3-month, 4-month, 5-month, and&#xD;
      6-month follow up). Subjects will be immunized during Weeks 0, 3, 6 and 18 with either&#xD;
      Oxy(Gly)4-sKLH (either 100 μg or 400 μg dose; different dose levels will be administered by&#xD;
      varying the volume of the 400 μg/mL formulation) adsorbed on aluminum adjuvant or aluminum&#xD;
      alone as placebo.&#xD;
&#xD;
      Screening Phase (Weeks -6 thru -2): Eligibility for admission into the study will be based on&#xD;
      a psychiatric evaluation, physical examination, blood and urine testing, electrocardiogram,&#xD;
      drug history assessment, urine drug testing, and ascertainment of physical dependence on&#xD;
      opioids via naloxone challenge and/or objective confirmation of opioid withdrawal&#xD;
      signs/symptoms&#xD;
&#xD;
      Inpatient Phases (Weeks -1-8 &amp; 18-19) Opioid Maintenance and Testing Sessions: During the&#xD;
      inpatient phases participants will be maintained on oral morphine 120 mg/day. During testing&#xD;
      sessions, intranasal oxycodone (0, 25, 50, and 100 mg/70kg) will be administered during each&#xD;
      inpatient phase to assess the ability of the vaccine to reduce positive subjective ratings&#xD;
      (e.g., Drug Liking, High, etc.). Intranasal heroin (100 mg/70 kg) and lactose powder&#xD;
      (placebo) will be used as positive and negative controls, respectively. In addition to&#xD;
      assessing subjective effects, vital signs and other physiological measures are collected&#xD;
      throughout the testing period (4.5 hours). The order ofthe different doses will be randomized&#xD;
      and one dose of either oxycodone, heroin, or placebo will be given each day on 5 consecutive&#xD;
      days. During testing sessions a physician or nurse practitioner will be on the floor for the&#xD;
      first hour after IN dosing, and on-call throughout the session.&#xD;
&#xD;
      Outpatient Phases (Weeks 9-17, 20-21): Participants will return to the laboratory weekly&#xD;
      during the outpatient phases in order to assess titer levels, maintain good contact and to&#xD;
      assess drug use, adverse events, and concomitant medication use. Blood tests (hematology,&#xD;
      chemistry) and urinalysis will be performed repeatedly throughout the study: just prior to&#xD;
      each inpatient phase and during the follow up visits at the end of the study (Weeks 8, 12,&#xD;
      17, 21, 23, and 30). In addition, the following assessments will be completed weekly&#xD;
      throughout the study: Physical exam, 12-lead ECG, body weight, vital signs, and standard&#xD;
      assessments of depression and suicidal thoughts/behaviors, along with cognitive functioning.&#xD;
      The Columbia Suicide Severity Rating Scale (CSSRS) and clinical interviews will be used to&#xD;
      provide ongoing assessments of this risk throughout the inpatient and outpatient phases of&#xD;
      the study.&#xD;
&#xD;
      Discharge (Week 19) and Follow-Up (Weeks 21, 23, 30, 34, 38, and 42): During the last week of&#xD;
      the study and/or prior to each inpatient discharge, participants will receive counseling&#xD;
      about different treatment options for opioid use disorder. For those participants requesting&#xD;
      treatment, appropriate arrangements will be made.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>Beginning from first vaccination through study completion (43 Weeks).</time_frame>
    <description>Safety and tolerability of the opioid vaccine.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of Vaccine on Intranasal Drug Positive Subjective Effects</measure>
    <time_frame>Throughout the testing session [i.e., pre-dose baseline (Time 0)- Thru- 4.5 hours post-dose].</time_frame>
    <description>Peak self-reported drug &quot;Liking.&quot; Measured using a visual analog scale (0-100).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Opioid-use Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo Vaccine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intranasal placebo 0mg</description>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxy 25 mg</intervention_name>
    <description>Intranasal oxycodone 25mg</description>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OXY 50 mg</intervention_name>
    <description>Intranasal oxycodone 50mg</description>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OXY 100 mg</intervention_name>
    <description>Intranasal oxycodone 100mg</description>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Heroin</intervention_name>
    <description>Intranasal heroin 100mg</description>
    <arm_group_label>High Dose Vaccine (400 μg)</arm_group_label>
    <arm_group_label>Low Dose Vaccine (100 μg)</arm_group_label>
    <arm_group_label>Placebo Vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          2. Males and females aged 18 to 59 years.&#xD;
&#xD;
          3. Females must be non-pregnant, non-lactating and either be of non-childbearing&#xD;
             potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1&#xD;
             year post-menopausal) or of childbearing potential but practicing a medically&#xD;
             acceptable method of birth control.&#xD;
&#xD;
          4. Meets current DSM 5 criteria for moderate-severe OUD, physical dependence on opioids,&#xD;
             and current use of opioids will be in amounts and/or frequencies that meet or exceed&#xD;
             those used in the study (3-4 tablets of a prescription opioid medication per day or&#xD;
             1-2 bags of heroin per day). Participants may meet criteria for other behavioral&#xD;
             disorders (e.g. gambling) or substance use disorders (e.g., cocaine or marijuana), but&#xD;
             cannot be physically dependent on drugs that pose risk of withdrawal that requires&#xD;
             medical management such as alcohol or benzodiazepines.&#xD;
&#xD;
             Participant must self-identify their opioid of choice as being other than oxycodone,&#xD;
             oxymorphone, hydrocodone, and hydromorphone (e.g., a heroin user). In addition, we&#xD;
             will only include individuals who have prior experience with intranasal opioid use.&#xD;
             Only participants with a minimum use of 1-2 bags of heroin per day and a maximum of 15&#xD;
             bags of heroin per day will be enrolled.&#xD;
&#xD;
          5. Not currently seeking treatment for drug use as defined by urine samples positive for&#xD;
             illicit opioids, and at least 2 urine samples negative for buprenorphine and&#xD;
             methadone, spaced at least 3 days apart, prior to admission.&#xD;
&#xD;
          6. Willing and able to comply with scheduled visits, dosing plan, laboratory tests, and&#xD;
             other study procedures.&#xD;
&#xD;
          7. Patients who weigh less than 300 pounds and /or have less than a maximum girth of 52&#xD;
             inches.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in a clinical trial and receipt of investigational drug(s) during 30&#xD;
             days (or 5 half-lives, whichever is longer) prior to randomization.&#xD;
&#xD;
          2. Sensitivity, allergy, or contraindication to opioids, alum, or any components of the&#xD;
             vaccine.&#xD;
&#xD;
          3. Prior exposure to opioid vaccines or vaccines containing Keyhole Limpet Hemocyanin.&#xD;
&#xD;
          4. Use of prescription psychotropic medications that would potentially interfere with&#xD;
             study procedures.&#xD;
&#xD;
          5. Women of childbearing age who are pregnant, lactating or, not practicing or willing to&#xD;
             begin a medically acceptable method of birth control.&#xD;
&#xD;
          6. Cannot read or understand the self-report assessment forms unaided or are so severely&#xD;
             disabled that they cannot comply with the requirements of the study.&#xD;
&#xD;
          7. Medical conditions that may make study participation hazardous:&#xD;
&#xD;
               -  History of seizures or cardiac risk conditions (unstable angina, cardiac&#xD;
                  arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling&#xD;
                  that the heart is beating too hard, too fast, skipping a beat, or fluttering).&#xD;
&#xD;
               -  Elevated liver function tests (i.e., AST and ALT &gt; 3 times the upper limit of&#xD;
                  normal).&#xD;
&#xD;
               -  Impaired renal function (creatinine &gt; 1.2).&#xD;
&#xD;
               -  Hypertension (&gt;140/90).&#xD;
&#xD;
               -  Asthmatic symptoms within the past 3 years.&#xD;
&#xD;
               -  Active hepatitis [e.g. symptomatic with a positive test for hepatitis B (HBsAg),&#xD;
                  hepatitis C antibody (HCV), HIV1/HIV2 antibody/antigen].&#xD;
&#xD;
               -  Significant hepatocellular injury as evidenced by elevated bilirubin levels&#xD;
                  (&gt;1.3), or elevated levels (over 3x the upper limit of normal) of aspartate&#xD;
                  aminotransferase (AST) and serum alanine aminotransferase (ALT).&#xD;
&#xD;
               -  Creatinine clearance estimated to be less than 60 ml/min.&#xD;
&#xD;
               -  Current gastric disease such as peptic ulcer disease, gastritis, upper&#xD;
                  gastrointestinal bleeding, or any gastrointestinal malignancy or precancerous&#xD;
                  condition.&#xD;
&#xD;
               -  Sleep apnea as assessed by the STOP-Bang questionnaire; those with high risk will&#xD;
                  be excluded from the study&#xD;
&#xD;
               -  Hemoglobin: Women &lt;11.5; men &lt;13.&#xD;
&#xD;
          8. Newly diagnosed HIV infection or known HIV infection with CD4 counts below normal&#xD;
             levels, active tuberculosis, or other immunocompromising diseases.&#xD;
&#xD;
          9. Current chronic pain (persistent for longer than 3 months).&#xD;
&#xD;
         10. Current or history of psychotic disorder or other severe Axis I disorder based on DSM&#xD;
             5 criteria, other than OUD, including physical dependence on drugs that pose risk of&#xD;
             withdrawal that requires medical management such as alcohol or benzodiazepines.&#xD;
&#xD;
             Participants diagnosed with dysthymia or mild-moderate depression with no recent&#xD;
             suicidal ideation may be included. Recent suicidal ideation&quot; is defined as thoughts&#xD;
             about suicide within the past month.&#xD;
&#xD;
         11. Previous serious or unexpected adverse reaction to a vaccine, including Guillain-Barré&#xD;
             syndrome.&#xD;
&#xD;
         12. Use of inhaled corticosteroids, antihistamines, immunosuppressive agents or other&#xD;
             medications within 30 days prior to administration of investigational product that&#xD;
             might interfere with an immune response.&#xD;
&#xD;
         13. Use of any vaccine, with the exception of influenza vaccine, 30 days prior to&#xD;
             administration of study product.&#xD;
&#xD;
         14. Known history of cancer or cancer treatment within 12 months prior to administration&#xD;
             of investigational product.&#xD;
&#xD;
         15. Receipt of blood products within 3 months of screening.&#xD;
&#xD;
         16. Anticipated inability to fulfill all visits and examination procedures throughout the&#xD;
             study period (approximately 12 months).&#xD;
&#xD;
         17. Individuals who are on medication-assisted treatment for Opioid Use Disorder (e.g.,&#xD;
             buprenorphine, buprenorphine/naloxone, methadone, naltrexone).&#xD;
&#xD;
         18. Individuals who currently (within the past 3 months) have a temporary restraining&#xD;
             order (TRO) against them or against another person.&#xD;
&#xD;
         19. Lactose is used as an excipient in the compounded challenge test articles.&#xD;
&#xD;
         20. History of prior opiate overdose (within the past 2 years) identified by self-report&#xD;
             during multiple interviews conducted during the screening process.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>59 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandra D Comer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jermaine Jones, PhD</last_name>
    <phone>16467746113</phone>
    <email>jermaine.jones@nyspi.columbia.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rachel Luba, PhD</last_name>
    <email>Rachel.Luba@nyspi.columbia.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Clinilabs Drug Development Corporation</name>
      <address>
        <city>Eatontown</city>
        <state>New Jersey</state>
        <zip>07724</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ronno Spanola, MS</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>New York State Psychiatric Institute: Division on Substance Use Disorders</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Sandra D. Comer</investigator_full_name>
    <investigator_title>Professor of Neurobiology (in Psychiatry)</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heroin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04458545
org study id: 7712
nct id: NCT04458545
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
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.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: Beginning from first vaccination through study completion (43 Weeks).
description: Safety and tolerability of the opioid vaccine.
measure: 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].
description: Peak self-reported drug "Liking." Measured using a visual analog scale (0-100).
arm group label: Placebo Vaccine
arm group type: Placebo Comparator
arm group label: Low Dose Vaccine (100 μg)
arm group type: Experimental
arm group label: High Dose Vaccine (400 μg)
arm group type: Experimental
intervention type: Drug
intervention name: Placebo
description: Intranasal placebo 0mg
arm group label: High Dose Vaccine (400 μg)
arm group label: Low Dose Vaccine (100 μg)
arm group label: Placebo Vaccine
intervention type: Drug
intervention name: Oxy 25 mg
description: Intranasal oxycodone 25mg
arm group label: High Dose Vaccine (400 μg)
arm group label: Low Dose Vaccine (100 μg)
arm group label: Placebo Vaccine
intervention type: Drug
intervention name: OXY 50 mg
description: Intranasal oxycodone 50mg
arm group label: High Dose Vaccine (400 μg)
arm group label: Low Dose Vaccine (100 μg)
arm group label: Placebo Vaccine
intervention type: Drug
intervention name: OXY 100 mg
description: Intranasal oxycodone 100mg
arm group label: High Dose Vaccine (400 μg)
arm group label: Low Dose Vaccine (100 μg)
arm group label: Placebo Vaccine
intervention type: Drug
intervention name: Heroin
description: Intranasal heroin 100mg
arm group label: High Dose Vaccine (400 μg)
arm group label: Low Dose Vaccine (100 μg)
arm group label: Placebo Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 59 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sandra D Comer, PhD
role: Principal Investigator
affiliation: New York State Psychiatric Institute
last name: Jermaine Jones, PhD
phone: 16467746113
email: jermaine.jones@nyspi.columbia.edu
last name: Rachel Luba, PhD
email: Rachel.Luba@nyspi.columbia.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Sandra D. Comer
investigator title: Professor of Neurobiology (in Psychiatry)
mesh term: Opioid-Related Disorders
mesh term: Heroin
sharing ipd: No