A Study to Evaluate the Efficacy and Safety of REL-1017 As Adjunctive Treatment of Major Depressive Disorder (MDD)

NCT06735079 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: REL-1017-305
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

Study Overview This clinical trial is a Phase 3 research study designed to test the safety and effectiveness of an investigational drug called REL-1017 (esmethadone HCl). The goal is to determine if REL-1017 can help people with major depressive disorder (MDD) who are already taking other antidepressant medications but have not experienced enough improvement. Why This Study Is Important MDD is a serious condition that affects mood, cognition, motivation, energy, and daily life. Some people do not respond fully to standard antidepressants. REL-1017 is being tested as an additional treatment to see if it can improve symptoms more effectively. Who Can Participate The study is enrolling adults diagnosed with major depressive disorder who do not have enough relief from their current antidepressant medications. Specific criteria must be met to join the study. What Happens in the Study Participants will be randomly assigned to receive either REL-1017 or a placebo (an inactive substance) along with their current antidepressant. This process helps researchers understand the effects of the drug. Neither the participants nor the researchers will know who receives REL-1017 or the placebo during the study. Study Details Duration: The study involves several weeks of treatment and follow-up visits. Assessments: Participants will complete health evaluations, including physical exams and questionnaires, to monitor progress and side effects. Costs: Study-related treatments and assessments are provided at no cost to participants. Potential Benefits and Risks Benefits: Participants may experience improvements in depressive symptoms. Risks: As with any investigational medication, there may be side effects. All participants will be closely monitored by the study team.

Conditions

Major Depressive Disorder (MDD)

Keywords

MDD; Esmethadone; Adjunctive therapy; REL-1017; NMDA

Outcome Measures

Primary Outcomes (1)

• MADRS10

  To evaluate the therapeutic efficacy of REL-1017 compared to placebo in participants with inadequate response to ongoing ADT at Day 28 on the Montgomery-Åsberg Depression Rating Scale (MADRS10) total score. Scale: Montgomery-Åsberg Depression Rating Scale (MADRS) Minimum and Maximum Values: The scale ranges from 0 to 60. Interpretation of Higher Scores: Higher scores indicate greater severity of depression. Specific Ranges: 0-6: Normal/no symptoms. 7-19: Mild depression. 20-34: Moderate depression. 35-60: Severe depression.

  28 days

Secondary Outcomes (4)

• MADRS10

  7 days

• MADRS10

  28 days

• MADRS10

  28 days

• CGI-S

  28 days

Study Arms (2)

REL 1017-305

EXPERIMENTAL

Drug: REL1017 (esmethadone HCI) (active drug)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

REL1017 (esmethadone HCI) (active drug) DRUG

REL-1017 is an investigational drug administered as an oral tablet, once daily. The dosing regimen includes a 75 mg dose on Day 1 (three tablets) in the clinic, followed by 25 mg daily (one tablet) at home from Day 2 to Day 28, with regular safety, efficacy, and tolerability assessments REL-1017 (esmethadone HCl) is under investigation as a novel NMDAR antagonist. Unlike racemic methadone, it lacks opioid-like effects such as dependency or respiratory depression. REL-1017 also lacks dissociative effects seen with more potent NMDAR antagonists such as ketamine. Finally, REL-1017 does not appear to have metabolic or neurological side effects.

REL 1017-305

Placebo DRUG

The placebo serves as a control to evaluate the effectiveness and safety of REL-1017. It is an inactive substance that matches the active drug in appearance but contains no active ingredients. The placebo group allows researchers to compare outcomes, such as changes in depressive symptoms, with the active drug group. The double-blind design ensures neither participants nor researchers know who is receiving the active treatment or placebo, eliminating bias. The placebo also helps assess whether observed side effects are due to the drug or unrelated factors. Participants are randomly assigned to receive either REL-1017 or the placebo, both administered once daily for 28 days. This helps establish REL-1017's clinical effectiveness and safety in treating Major Depressive Disorder (MDD).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Male or female participant, aged 18 to 65 years, inclusive, at Screening.
• Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive, at Screening.
• Participant understands the study requirements, is willing and able to commit to meet all study requirements, adhere to both approved ADT and study drug regimen, and complete all assessments and all scheduled visits, per Investigator judgment.

You may not qualify if:

• History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the participant or the validity of the study results, including established QT prolongation, long QT syndrome, torsades de pointes, bradyarrhythmia, ventricular tachycardia, uncompensated heart failure (greater than NYHA Class 1 CHF), uncontrolled hypokalemia, or uncontrolled hypomagnesemia.
• Any medical, psychiatric condition, or social context that, in the opinion of the Investigator, is likely to unfavourably alter the risk-benefit of participant, to interfere with protocol compliance, or to confound safety or efficacy assessments.
• Triplicate 12-lead ECG with average QTcF ≥450 msec, and/or a QRS interval ≥120 msec at Screening.

Sponsors & Collaborators

• MGGM LLC: lead

Study Sites (2)

Mediolanum Cardio Research

Milan, Italy, 20123, Italy

Location

Clinical Trial Unit - Ente Ospedaliero Cantonale (CTU-EOC) Area Formazione medica e Ricerca (AFRi)

Lugano, Switzerland, 6900, Switzerland

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 16, 2024
• Study Start: December 27, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); IT (1)