Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder

Opioid Use Disorder Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06384157
• Other study ID #: INDV-2000-201
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Indivior Inc.
• Contact: Global Director Clinical Development
• Phone: (804) 594-4488
• Email: trialdisclosure[@]indivior.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: September 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 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 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 taper on study (Study Day 7)

2. The participant recently completed medically supervised withdrawal outside

of the study, and:

• Time elapsed between last dose of TM buprenorphine and Study Day 1/randomization does not exceed 10 calendar days
• Recently completed opioid agonist treatment does not exceed 35 days of TM buprenorphine dosing days (inclusive of medically assisted withdrawal dosing and the study taper week [Study Day 7])

5. Male participants who are sexually active with individuals who are of childbearing potential must agree to use a medically acceptable form of contraception from Screening until at least 90 days after the last dose of study medication.

6. Female participant of non-childbearing potential; or a female 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, she is not pregnant as confirmed by a negative serum screening and or urine human chorionic gonadotrophin test on Study Day 1, and 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 1 time per week.

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:

1. Uncontrolled arrhythmias

2. History of congestive heart failure

3. Myocardial infarction <6 months from receipt of first dose of investigational medicinal product (IMP)

4. Uncontrolled symptomatic angina

5. 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:

1. Total bilirubin =1.5×upper limit of normal (ULN) (with direct bilirubin >1.3 mg/dL)

2. Alanine aminotransferase (ALT) =3×ULN

3. Aspartate aminotransferase (AST) =3×ULN

4. International normalized ratio (INR) >1.2×ULN

5. 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 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 (i.e., 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.

21. Current incarceration, treatment for OUD required by court order, or pending incarceration/legal action that could prevent participation or compliance in the study.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders
• Substance-Related Disorders

Intervention

Drug:
• INDV-2000
INDV-2000 is a highly potent and selective OX1R antagonist that is being developed as a therapy for the treatment of OUD.

Other:
• Placebo
This is a randomized, double-blind, placebo-controlled study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Indivior Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion (probability) of participants without treatment failure by the end of Week 12 (Day 85).	The treatment failure is defined as meeting either one of the two criteria.; Urine Drug Screen (UDS, dipstick) positive for opioids, or fentanyl on 4 consecutive assessments while participants on the Investigational Medicinal Product (IMP) (INDV-2000 or placebo) alone (after Day 8 visit).; Discontinued the IMP (INDV-2000 or placebo) prematurely.	12 weeks
Secondary	Proportion (probability) of visits with opioid abstinence while participants are on IMP alone.	Abstinence is based on negative UDS and self-report use.	From Week 1 to Week 13
Secondary	Participant's percentage of visits with opioid abstinence during the whole study follow-up.	Abstinence is based on negative UDS and self-report use.	13 Weeks
Secondary	Incidence, severity and relatedness of adverse events, treatment-emergent adverse events, serious adverse events and events leading to discontinuation and deaths.	Number of participants reporting adverse events	17 weeks
Secondary	Opioid Craving Assessment	7-item self-reported instrument to assess the participant's craving in the past week, on a likert scale of 1 to 7 (Strongly Disagree as 1, Disagree, Slightly Disagree, Neither Agree nor Disagree, Slightly Agree, Agree, or Strongly Agree as 7). The 7 questions assess general craving, and the following 6 dimensions: preoccupation or obsessive thoughts, anticipation of negative reinforcement, anticipation of positive reinforcement, motivation, drive and intention to use opioids, feeling lack of control or automaticity, and feeling uneasiness related to opioid use.	13 Weeks
Secondary	Cmax on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	Tmax on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	AUC0-24 on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	Cavg on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	Cmin on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	CL/F on Day 1 and Day 15/16	PK sampling are done under the PK Substudy	2 Weeks
Secondary	Clinical Opiate Withdrawal Scale (COWS) score	The COWS is an 11-item, validated instrument used to assess symptoms of opiate withdrawal. The score is the sum of the response to each of the 11 items and ranges from 0 to 48. A score of 5 to 12 is considered mild, 13 to 24 is moderate, 25 to 36 is moderately severe, and a score >36 is considered severe withdrawal.	4 weeks