Clinical trial NCT06384157: Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder
Official title: A Phase II Double Blind, Placebo Controlled, Randomised, Dose-Ranging Study to Assess the Safety and Efficacy of INDV-2000 Over 3 Months in Treatment Seeking Individuals With Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure safety and efficacy and to determine dose-response relationship for INDV-2000 in participants with moderate to severe Opioid Use Disorder (OUD) who are new to treatment, have recently initiated or completed short-term medically supervised withdrawal with transmucosal (TM) buprenorphine, and are interested in transitioning to a non opioid treatment.

Detailed description: From Day 1 to Day 7, TM buprenorphine and randomized INDV-2000/Placebo will be administered, INDV-2000/Placebo will be administered alone from Day 8 onward. The randomized treatment period starts when the participant receives randomized treatment (at Day 1) and ends at his/her last study visit, if on INDV-2000/Placebo alone, or ends when starting buprenorphine rescue therapy.

Eligibility criteria: Inclusion Criteria:

* Participants are eligible to be included in the study only if all of the following criteria apply:

  1. Participant must be 18 or the legal age of consent in the jurisdiction in which the study is taking place to 65 years of age inclusive, at the time of signing the informed consent.
  2. Able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, be able to comply with protocol requirements, rules and regulations of study site, and be likely to complete all the study interventions.
  3. Males or females with moderate or severe opioid use disorder (OUD) by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who are looking to transition from daily short-term opioid agonist treatment (medically supervised withdrawal) to non-opioid treatment.
  4. Have not been on medication for opioid use for 3 months prior to the current treatment episode, and satisfies either a or b below.

     1. The participant will initiate, or is undergoing medically supervised withdrawal, and

        * In the opinion of the investigator, the participant is able to achieve a stable dose of transmucosal (TM) buprenorphine between ≤24 mg inclusive prior to randomization.
        * Current opioid agonist treatment does not exceed 35 days from the start of TM buprenorphine to the end of Screening window.
     2. The participant recently completed medically supervised withdrawal outside of the study, and

        * Time elapsed between last dose of TM buprenorphine or other withdrawal medication and Study Day 1/randomization does not exceed 21 calendar days.
        * Recently completed opioid agonist treatment does not exceed 35 days of TM buprenorphine dosing days inclusive of medically assisted withdrawal dosing.
  5. Male participants who are sexually active with individuals who are of childbearing potential must agree to use a medically acceptable forms of contraception from Screening until at least 90 days after the last dose of study medication. The following methods of contraception are considered to be medically acceptable: established use of oral, injected or implanted hormonal contraception; placement of an intrauterine device or intrauterine system; or use of a double barrier method of contraception (condom or occlusive cap with use of a spermicide), or abstinence.
  6. A female participant of non-childbearing potential, or a male of childbearing potential if

     * She agrees to use a medically acceptable form of contraception from Screening until at least 90 days after the last dose of study medication. The following methods of contraception are considered to be medically acceptable: abstinence; established use or oral, injected or implanted hormonal contraception; placement of an intrauterine device or intrauterine system; or use of a double barrier method of contraception (condom or occlusive cap with use of a spermicide).
     * She is not pregnant as confirmed by a negative serum screening and or urine human chorionic gonadotrophin test on Study Day 1.
     * She is not lactating.
  7. Body mass index (BMI) within 18.0 to 40.0 kg/m2 (inclusive)

Exclusion Criteria:

* Participants are excluded from the study if any of the following criteria apply:

  1. Have a current diagnosis, other than OUD, requiring chronic opioid treatment.
  2. Have a concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis or alcohol use disorders.
  3. Meet DSM-5 criteria for severe substance use disorder other than opioids.
  4. Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder that would impact participation in the study as judged by an Investigator or medically responsible physician.
  5. Had an opioid overdose event within the 6 months prior to the Screening Visit.
  6. Uses any substance of abuse via the injection route more than 2 times per week over the last 3 months prior to Screening.
  7. Have clinically significant abnormal biochemistry, hematology or urinalysis results that would impact participation in the study as judged by an Investigator or medically responsible physician.
  8. Have a history of narcolepsy, cataplexy, obstructive or central sleep apnea.
  9. Have disorders that may interfere with drug absorption, distribution, metabolism and excretion processes.
  10. History of suicidal ideation within 30 days prior to providing written informed consent as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at the Screening Visit or history of a suicide attempt (per the C-SSRS) in the 6 months prior to informed consent.
  11. Serious cardiac illness or other cardiac assessments including, but not limited to:

      * Uncontrolled arrhythmias.
      * History of congestive heart failure.
      * Myocardial infarction \<6 months from receipt of first dose of investigational medicinal product (IMP)
      * Uncontrolled symptomatic angina
      * QT interval corrected with Fridericia's formula (QTcF) \>450 msec for males and \>470 msec for females or history of prolonged QT syndrome.
  12. Have any combination of the following at screening:

      * Total bilirubin ≥1.5×upper limit of normal (ULN) (with direct bilirubin \>1.3 mg/dL),
      * Alanine aminotransferase (ALT) ≥3×ULN
      * Aspartate aminotransferase (AST) ≥3×ULN
      * International normalized ratio (INR) \>1.2 for participants not receiving anticoagulation therapy, \>3.0 for participants on conventional coagulation therapy, \>3.5 for participants on intensive anticoagulation, or
      * Estimated glomerular filtration rate \<60 mL/min by Cockroft-Gault formula.
  13. Current symptomatic hepatic or biliary disease, including participants with cholecystectomy \<90 days prior to Screening.
  14. Use of a long-acting buprenorphine or naltrexone treatment for OUD within 2 years or 1 year of the screening visit, respectively.
  15. Concurrent treatment or treatment with an investigational drug, or participation in any other clinical study within 30 days prior to the signing the informed consent form.
  16. Blood or platelets donation of greater than 500 mL within 56 days or plasma donation within 7 days of screening; clinically significant anemia or low hemoglobin (\<11 g/dL for females, \<12 g/dL for males).
  17. Known allergy or hypersensitivity to IMP or its excipients.
  18. Any condition that, in the opinion of an Investigator or medically responsible physician, would interfere with evaluation of the IMP or interpretation of participant safety or study results.
  19. Is a member of site staff, has a financial interest in Indivior, or is an immediate family member of anyone directly involved in the study (ie, site staff, Indivior, or Clinical Research Organization \[CRO\] employee).
  20. Participants who are unable, in the opinion of an Investigator or medically responsible physician, to comply fully with the study requirements, including prohibited concomitant therapies.
  21. Current incarceration, treatment for OUD required by court order, or pending incarceration/legal action that could prevent participation or compliance in the study.

Primary outcomes:
measure: Proportion (probability) of participants without treatment failure by the end of Week 12 (Day 85).
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion (probability) of visits with opioid abstinence while participants are on IMP alone.
timeFrame: From Week 1 to Week 13
measure: Participant's percentage of visits with opioid abstinence during the whole study follow-up.
timeFrame: 13 Weeks
measure: Incidence, severity and relatedness of adverse events, treatment-emergent adverse events, serious adverse events and events leading to discontinuation and deaths.
timeFrame: 17 weeks
measure: Opioid Craving Assessment
timeFrame: 13 Weeks
measure: Cmax on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: Tmax on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: AUC0-24 on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: Cavg on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: Cmin on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: CL/F on Day 1 and Day 15/16
timeFrame: 2 Weeks
measure: Clinical Opiate Withdrawal Scale (COWS) score
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Hamilton
country: United States
facility: Boyett Health Services Inc
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Oceanside
country: United States
facility: North County Clinical Research
state: California
city: Pomona
country: United States
facility: Empire Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research - San Diego
state: California
city: Boynton Beach
country: United States
facility: Imagine Research of Palm Beach County
state: Florida
city: Jacksonville
country: United States
facility: Bold City Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: Vitalix Kissimmee
state: Florida
city: Lakeland
country: United States
facility: Accel Research Sites - Lakeland
state: Florida
city: Miami Beach
country: United States
facility: Quantum Clinical Trials
state: Florida
city: Miami Lakes
country: United States
facility: Segal Trials Miami Lakes
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Baltimore
country: United States
facility: Maryland Treatment Centers
state: Maryland
city: Worcester
country: United States
facility: Vitalix Clinical
state: Massachusetts
city: Flint
country: United States
facility: Insight Research Institute
state: Michigan
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Saint Louis
country: United States
facility: Arch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: IMA Clinical Research
state: Nevada
city: Las Vegas
country: United States
facility: Oasis Clinical Research
state: Nevada
city: Bronx
country: United States
facility: Dr Vando Medical Services
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Morehead City
country: United States
facility: West Clinical Research
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research Center, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Pahl Pharmaceutical Professionals, LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: SP Research PLLC Rivus Wellness and Research Insitute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Unity Clinical Research
state: Oklahoma
city: Greenville
country: United States
facility: Prisma Health Addiction Medicine Center
state: South Carolina
city: DeSoto
country: United States
facility: Insite Clinical Research, LLC
state: Texas
city: El Paso
country: United States
facility: El Paso Clinical Trials
state: Texas
city: Houston
country: United States
facility: HD Research
state: Texas
city: Bountiful
country: United States
facility: Progressive Clinical Research Llc
state: Utah
city: Clinton
country: United States
facility: Alpine Research Organisation
state: Utah
city: Provo
country: United States
facility: Boeson Clinical Research
state: Utah
Study officials:
affiliation: Indivior Inc.
name: Global Director Clinical Development
role: STUDY_DIRECTOR
References: