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

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-I 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: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: REL-1017

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33175
      • Relmada Site
    • Miami Springs, Florida, United States, 33166
      • Relmada Site
    • Palm Bay, Florida, United States, 32905
      • Relmada Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Relmada Site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Relmada Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Relmada Site
    • Watertown, Massachusetts, United States, 02472
      • Relmada Site
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Relmada Site
  • New York
    • New York, New York, United States, 10128
      • Relmada Site
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Relmada Site
  • Texas
    • Austin, Texas, United States, 78737
      • Relmada Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults 18 to 65 years, inclusive.
• Diagnosed with Major Depressive Disorder (MDD) based on structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (SCID-5) for MDD.
• Current major depressive episode.
• With inadequate response to 1-3 first-line antidepressants administered at an adequate and stable dose

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.
• Acute or chronic condition that, in the Investigator's opinion, would limit the subject's ability to complete or participate in this clinical study.
• Prior participation in a ketamine, esketamine, dextromethorphan or any other NMDAR- antagonist study, or received esketamine at any time.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REL-1017; A 75 mg REL-1017 loading dose (three 25 mg REL-1017 tablets) will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 25 mg REL-1017 in addition to their ongoing antidepressant.	Drug: REL-1017; REL-1017 tablet; Other Names: esmethadone
Placebo Comparator: Placebo; Three tablets of matching placebo will be administered on Day-1 of the 28-day treatment period. From Day-2 to Day-28, participants will take 1 placebo tablet in addition to their ongoing antidepressant.	Drug: Placebo; Placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the MADRS10 Total Score From Baseline to 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. The overall score ranges from 0 to 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS10 Remission Rate (Total Score ≤10) at Day 28	Therapeutic remission rate with REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Remission is defined as MADRS10 Total Score ≤10 at Day 28. A higher percentage of remission indicates a higher percentage of subjects with MADRS10 Total Score ≤10 at Day 28.	Day 28
MADRS10 Response Rate (Improvement ≥50% Compared With Total Baseline Score) at Day 28	Therapeutic response to REL-1017 as adjunctive treatment versus placebo in the Montgomery-Asberg Depression Rating Scale (MADRS10). Response rate is defined as an improvement ≥50% compared with total Baseline MADRS10 score.	Day 28

Collaborators and Investigators

• Sponsor: Relmada Therapeutics, Inc.
• Investigators: Study Director: Marco Pappagallo, MD, Relmada Therapeutics

Publications and helpful links

Helpful Links

• Study Homepage

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2021
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: REL-1017
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: REL-1017-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No