A Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment for Major Depressive Disorder (MDD) (RELIANCE-II)

June 15, 2026 updated by: Levomecor Inc.

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study to Assess the Efficacy and Safety of REL-1017 as Adjunctive Treatment of Major Depressive Disorder (The RELIANCE-II Study)

This is an outpatient, 2-arm, Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of REL-1017 once daily (QD) as an adjunctive treatment of Major Depressive Disorder. Study participants will continue to take their current antidepressant therapy in addition to the study drug or placebo for the duration of the treatment period.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

236

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Homewood, Alabama, United States, 35209
        • Relmada Site
    • Arizona
      • Chandler, Arizona, United States, 85226
        • Relmada Site
      • Chandler, Arizona, United States, 85286
        • Relmada Site
      • Phoenix, Arizona, United States, 85016
        • Relmada Site
      • Tucson, Arizona, United States, 85704
        • Relmada Site
    • Arkansas
      • Bryant, Arkansas, United States, 72022
        • Relmada Site
    • California
      • Anaheim, California, United States, 92805
        • Relmada Site
      • Bellflower, California, United States, 90706
        • Relmada Site
      • Encino, California, United States, 91316
        • Relmada Site
      • Lafayette, California, United States, 94549
        • Relmada Site
      • Los Angeles, California, United States, 90015
        • Relmada Site
      • Newport Beach, California, United States, 92660
        • Relmada Site
      • Orange, California, United States, 92868
        • Relmada Site
      • Redlands, California, United States, 92374
        • Relmada Site
      • Santa Ana, California, United States, 92705
        • Relmada Site
      • Stanford, California, United States, 94305
        • Relmada Site
      • Temecula, California, United States, 92591
        • Relmada Site
      • Upland, California, United States, 91786
        • Relmada Site
    • Colorado
      • Denver, Colorado, United States, 80209
        • Relmada Site
    • Florida
      • Brandon, Florida, United States, 33511
        • Relmada Site
      • Hialeah, Florida, United States, 33015
        • Relmada Site
      • Jacksonville, Florida, United States, 32256
        • Relmada Site
      • Maitland, Florida, United States, 32751
        • Relmada Site
      • Miami, Florida, United States, 33133
        • Relmada Site
      • Miami, Florida, United States, 33174
        • Relmada Site
      • Miami, Florida, United States, 33122
        • Relmada Site
      • Miami, Florida, United States, 33125
        • Relmada Site
      • Miami, Florida, United States, 33136
        • Relmada Site
      • Miami Springs, Florida, United States, 33166
        • Relmada Site
      • Okeechobee, Florida, United States, 34972
        • Relmada Site
      • Tampa, Florida, United States, 33607
        • Relmada Site
      • West Palm Beach, Florida, United States, 33407
        • Relmada Site
    • Georgia
      • Savannah, Georgia, United States, 31406
        • Relmada Site
    • Idaho
      • Boise, Idaho, United States, 83704
        • Relmada Site
    • Illinois
      • Chicago, Illinois, United States, 60634
        • Relmada Site
      • Chicago, Illinois, United States, 60611
        • Relmada Site
      • Elgin, Illinois, United States, 60123
        • Relmada Site
    • Kansas
      • Overland Park, Kansas, United States, 66210
        • Relmada Site
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Relmada Site
    • Maryland
      • Baltimore, Maryland, United States, 21208
        • Relmada Site
      • Bel Air, Maryland, United States, 21015
        • Relmada Site
      • Gaithersburg, Maryland, United States, 20877
        • Relmada Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02131
        • Relmada Site
    • Michigan
      • Bloomfield Hills, Michigan, United States, 48302
        • Relmada Site
    • Minnesota
      • Mankato, Minnesota, United States, 56001
        • Relmada Site
    • Missouri
      • Weldon Spring, Missouri, United States, 63304
        • Relmada Site
    • Nevada
      • Las Vegas, Nevada, United States, 89121
        • Relmada Site
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Relmada Site
    • New York
      • Cedarhurst, New York, United States, 11516
        • Relmada Site
    • North Carolina
      • Monroe, North Carolina, United States, 28112
        • Relmada Site
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Relmada Site
      • Cincinnati, Ohio, United States, 45215
        • Relmada Site
      • Cincinnati, Ohio, United States, 45219
        • Relmada Site
      • Westlake, Ohio, United States, 44145
        • Relmada Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Relmada Site
      • State College, Pennsylvania, United States, 16801
        • Relmada Site
    • Tennessee
      • Memphis, Tennessee, United States, 38119
        • Relmada Site
    • Texas
      • Austin, Texas, United States, 78737
        • Relmada Site
      • Austin, Texas, United States, 78759
        • Relmada Site
      • Beaumont, Texas, United States, 77702
        • Relmada Site
      • Bellaire, Texas, United States, 77401
        • Relmada Site
      • Dallas, Texas, United States, 75243
        • Relmada Site
      • Friendswood, Texas, United States, 77546
        • Relmada Site
      • Houston, Texas, United States, 77081
        • Relmada Site
      • Sherman, Texas, United States, 75092
        • Relmada Site
      • Wichita Falls, Texas, United States, 76309
        • Relmada Site
    • Utah
      • Draper, Utah, United States, 84020
        • Relmada Site
    • Vermont
      • Rutland, Vermont, United States, 05701
        • Relmada Site
    • Virginia
      • Portsmouth, Virginia, United States, 23703
        • Relmada Site
    • Washington
      • Everett, Washington, United States, 98201
        • Relmada Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Body mass index (BMI) between 18.0 and 35.0 kg/m2.
  • Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD.
  • Current Major Depressive Episode (MDE).
  • Treated on approved, stable first-line anti-depressant therapy with inadequate response to 1 to 3 valid courses of treatment with a depressant medication in the current MDE.

Exclusion Criteria:

  • Any current and primary psychiatric disorder other than Major Depressive Disorder.
  • Severe alcohol or substance use disorder.
  • History of bipolar I and II disorder, psychosis, and/or mania.
  • Poorly controlled diabetes as defined by HbA1c > 7.5%, despite standard care. Subjects with HbA1c >7.5% may continue in the study if approved by the Relmada Medical Monitor.
  • Having received ketamine or esketamine within 60 days prior to Screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
During the double blind treatment period (28 days), participants will take 1 tablet of placebo, orally, per day in addition to their ongoing antidepressant (ADT).
Drug: Placebo
Placebo tablet
Experimental: REL-1017 25 mg
During the double blind treatment period (28 days), participants will take 1 tablet of REL-1017 25 mg, orally, per day in addition to their ongoing antidepressant (ADT)
Drug: REL-1017
REL-1017 tablet
Other Names:
  • Esmethadone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Day 28 in MADRS Total Score
Time Frame: Baseline and Day 28
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. The total score is calculated as the sum of 10 items, each scored from 0 to 6, resulting in a total score range of 0 to 60. Lower scores indicate less severe depressive symptoms and a better outcome, whereas higher scores indicate more severe depressive symptoms and a worse outcome. The outcome measure reports the change in MADRS total score from Baseline to Day 28. Change was calculated as Day 28 score minus Baseline score.
Baseline and Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Day 7 in MADRS Total Score
Time Frame: Day 7
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. The total score is calculated as the sum of 10 items, each scored from 0 to 6, resulting in a total score range of 0 to 60. Lower scores indicate less severe depressive symptoms and a better outcome, whereas higher scores indicate more severe depressive symptoms and a worse outcome. The outcome measure reports the change in MADRS total score from Baseline to Day 7. Change was calculated as Day 7 score minus Baseline score.
Day 7
Change From Baseline to Day 28 in Clinical Global Impression-Severity (CGI-S) Score
Time Frame: Day 28
Clinical Global Impression-Severity (CGI-S) is a clinician-rated assessment of illness severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Lower scores indicate less severe illness and a better outcome, whereas higher scores indicate more severe illness and a worse outcome. The outcome measure reports the change in CGI-S score from Baseline to Day 28. Change was calculated as Day 28 score minus Baseline score
Day 28
MADRS10 Remission Rate at Day 28
Time Frame: Day 28
Remission was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score ≤10 at Day 28. The MADRS total score ranges from 0 to 60, with lower scores indicating less severe depressive symptoms and a better outcome.
Day 28
MADRS10 Response Rate at Day 28
Time Frame: Day 28
Response was defined as a ≥50% reduction from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. The MADRS total score ranges from 0 to 60, with lower scores indicating less severe depressive symptoms and a better outcome.
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Levomecor Inc.

Investigators

  • Study Director: Paul Greene, PhD, Relmada Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2021

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

January 14, 2025

Study Registration Dates

First Submitted

April 19, 2021

First Submitted That Met QC Criteria

April 19, 2021

First Posted (Actual)

April 22, 2021

Study Record Updates

Last Update Posted (Actual)

July 10, 2026

Last Update Submitted That Met QC Criteria

June 15, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REL-1017-302

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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