Clinical Trials of Multivalent Opioid Vaccine Components

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.

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