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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Major Depressive Disorder, Depression

Intervention / Treatment
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* Drug: REL-1017
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 to 65 years, inclusive. Diagnosed with Major Depressive Disorder (MDD) based on Structured Clinical Interview for DSM-5 (SCID-5) for MDD. Current major depressive episode. Treated on approved, stable first-line anti-depressant therapy with inadequate response to 1 to 3 valid courses of treatment with an antidepressant medication 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. Any lifetime experience of having received ketamine or esketamine as a treatment for MDD, or as part of a clinical trial.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REL-1017 25 mg<br>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<br>* REL-1017 tablet<br>* Other names: esmethadone;|
| Placebo Comparator: Placebo<br>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<br>* Placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the MADRS10 total score | 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 Oto 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 |
| --- | --- | --- |
| Change in CGI-S score | 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 | 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 Oto 60 with scores above 34 indicating severe depression. A negative change from baseline indicates improvement. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REL-1017, Relmada, NMDA receptor antagonist, esmethadone, adjunctive, antidepressant, Reliance, Depression