OXD01 in Combination With Sublingual Buprenorphine/Naloxone for Treatment of Opioid Use Disorder

Study Overview
=================
Brief Summary
-----------------
This is an open-label, randomized, parallel-group multicenter study designed to evaluate the efficacy of the digital therapeutic OXD01 (MODIA) combined with sublingual buprenorphine/naloxone standard of care (SL BUP/NAL SOC) background therapy compared to SL BUP/NAL alone to change opioid use patterns in subjects with OUD. Approximately 400 subjects will be randomized. The study will include a screening visit and a randomization visit, followed by 24 weeks of study treatment. Subjects will be scheduled for evaluation visits, which will include a UDS and a self report of drug use, weekly during the first four weeks of treatment, then every other week from weeks 5 through 12, then monthly through week 25. Subjects will also return to the site for only a urine drug screen (UDS) and a self-report of drug use each week between the evaluation visits. The primary objective of the study is to determine whether the combination of sublingual (SL) buprenorphine/naloxone (BUP/NAL) standard of care (SOC) background therapy and the digital therapeutic OXD01 is superior to SL BUP/NAL alone to reduce opioid use.

Detailed Description
-----------------
Medication-assisted treatment, the current standard for opioid addiction, is the use of medications in combination with counseling and behavioral therapies to provide a whole-patient approach to the treatment of opioid use disorder (OUD). However, patients may not have optimal access to faceto-face clinical behavioral health services. Digital therapeutics can help bridge the gap between accessible services and optimal treatment of OUD, the primary goal of which is to reduce the use of opioids. OXD01 is a device-based digital therapeutic, designed to offer individuals diagnosed with OUD quality psychotherapy intervention based on cognitive behavioral therapy and motivational interviewing. This study is being conducted to determine the value of OXD01 when combined with medication to change opioid use patterns in subjects with OUD. Note: No investigational product will be administered as part of this study.

Official Title
-----------------
A Randomized, Open-label, Parallel-group Study to Evaluate the Efficacy of the Digital Therapeutic OXD01 (MODIA™) in Combination With Sublingual Buprenorphine/Naloxone for the Treatment of Opioid Use Disorder

Conditions
-----------------
Opioid-use Disorder

Intervention / Treatment
-----------------
* Device: OXD01 digital therapy
* Other: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female 18 - 65 years of age at the screening visit, fluent in English and able to read, comprehend, and willingly sign the informed consent form (ICF). Voluntarily seeking treatment for OUD. In the judgment of the Investigator has the appropriate hearing, vision, manual dexterity, ability to understand instructions, and ability to use and understand internet-based applications. Currently meets the criteria for moderate or severe opioid use disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-V (Appendix B). Has a positive UDS for opioids at screening that is consistent with their drug use history. In good health as determined by lack of clinically significant abnormalities in health assessments performed at screening. Agrees not to take any buprenorphine products other than those prescribed by the Investigator during participation in the study, and agrees to use OXD01 as directed if randomized to that treatment group. Completed SL BUP/NAL induction, with physical withdrawal symptoms reduced so the subject is able to fulling participate in OXD01 training, if randomized to that treatment group, and is no greater than 14 days from the first dose of SL BUP/NAL induction. Exclusion Criteria: 1. Unwilling or unable to comply with the requirements of the protocol or are in a situation or condition that, in the opinion of an Investigator, may interfere with participation in the study (e.g., does not have reliable internet access). 2. History of allergy or sensitivity to naloxone, buprenorphine or other opioids, or history of any drug hypersensitivity or intolerance which, in the opinion of an Investigator, would compromise the safety of the subject. 3. Used an investigational drug within 30 days or 5 half-lives (whichever is greater) prior to randomization. 4. Received prescribed medication-assisted treatment with buprenorphine, methadone, or naltrexone for opioid use disorder within 14 days prior to screening. 5. Past or present diseases that, judged by an Investigator and based on available medical history/records, may jeopardize the safety of the subject or impact the validity of the study results. 6. Tongue piercing, or piercings in the mouth or oral deformities that may affect sublingual absorption, in the opinion of an Investigator. 7. Hospitalization for a psychiatric disorder in the past 30 days, not including inpatient treatment for drug rehabilitation. 8. Schizophrenia, or other serious mental illness defined as a mental, behavioral, or emotional disorder resulting in serious functional impairment which substantially interferes with or limits participation in the study. 9. A Quick Inventory of Depression Symptoms - Self-Report (QIDS-SR, Appendix C) score ≥ 16 (severe depression) or a rating of 2 or 3 for question 12 (Thoughts of Death or Suicide) at screening. 10. A current diagnosis, other than opioid use disorder, requiring chronic opioid treatment. 11. Chronic pain that is unremitting or unstable. 12. Current DSM-V diagnosis of moderate to severe substance use disorder for psychoactive substances other than opioids, caffeine, marijuana, or nicotine. 13. Requires current use of medications that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4 (Section 4.3.1). 14. Any pending legal action that could affect participation or compliance in the trial. 15. Is an employee of the Investigator or the trial site, with direct involvement in the proposed trial or other trials under the direction of the Investigator or trial site, or is a family member of the Investigator or an employee.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: SL BUP/NAL SOC background therapy<br>standard of care. Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice. | Other: Standard of Care<br>* sublingual buprenorphine/naloxone Medication-assisted treatment, the current standard for opioid addiction; the use of medications in combination with counseling<br>|
| Experimental: SL BUP/NAL + OXD01<br>standard of care + OXD01 (digital therapy). Subjects in both groups will receive the assigned treatment for 24 weeks. Subjects in both groups may also be encouraged to participate in behavioral health therapies in accordance with the Investigator's standard of practice. | Device: OXD01 digital therapy<br>* OXD01 digital therapy, 1-2 times per week 15-30 minutes each time.<br>Other: Standard of Care<br>* sublingual buprenorphine/naloxone Medication-assisted treatment, the current standard for opioid addiction; the use of medications in combination with counseling<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of Opioid use | The primary objective of the study is to determine whether the combination of sublingual (SL) buprenorphine/naloxone (BUP/NAL) standard of care (SOC) background therapy and the digital therapeutic OXD01 is superior to SL BUP/NAL alone for the change of opioid use. | from week 6 to week 25 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
digital therapy, cognitive behavioral therapy, CBT