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

November 5, 2025 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 in the MADRS10 total score
Time Frame: Day 28

Therapeutic efficacy of REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). A higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6.

A negative change from baseline indicates improvement.
Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CGI-S score
Time Frame: Day 28

Therapeutic efficacy of REL-1017 as an adjunctive treatment versus placebo in Clinical Global Impression of Severity (CGI-S). The CGI-S is a standard method used in clinical studies to quantify and track patient progress and treatment response over time. The scale is composed of 7 ratings: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients.

The score ranges from 1 to 7, and a lower CGI-S score indicates lower levels of depression.
Day 28
Change in the MADRS10 total score
Time Frame: Day 7
MADRS10 score at Day 7.
Day 7
MADRS10 Remission Rate
Time Frame: Day 28
MADRS10 remission rate (total score ≤10) at Day 28
Day 28
MADRS10 Response Rater
Time Frame: Day 28
Improvement ≥50% compared with total Baseline score) at Day 28
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 (Estimated)

November 6, 2025

Last Update Submitted That Met QC Criteria

November 5, 2025

Last Verified

January 1, 2025

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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