REL-1017 for Depression

(RELIANCE-II Trial)

No longer recruiting at 109 trial locations

Overseen By Senior Vice President

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Levomecor Inc.

Must be taking: Antidepressants

Must not be taking: Ketamine, Esketamine

Disqualifiers: Bipolar, Psychosis, Mania, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called REL-1017 for individuals with Major Depressive Disorder (MDD) who continue to experience symptoms despite taking antidepressants. The study aims to determine if REL-1017 can enhance depression treatment when added to existing medication. Participants will receive either the new drug or a placebo, alongside their usual antidepressant, for 28 days. Suitable candidates include those diagnosed with MDD, currently experiencing a depressive episode, and not responding well to their current antidepressant regimen. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current antidepressant medications. Participants will continue their current antidepressant therapy along with the study drug or placebo.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that REL-1017 has been tested for safety in people with major depressive disorder. In a year-long study, participants used REL-1017 daily, either alone or with other antidepressants. This study provided important safety information.

Some participants experienced side effects, but few discontinued the treatment because of them, indicating that REL-1017 was generally well-tolerated.

Another study found that depression symptoms improved without major safety issues, suggesting its potential for use with other antidepressants.

Overall, the evidence suggests REL-1017 is quite safe for many people. However, as with any treatment, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

REL-1017 is unique because it works differently from most standard antidepressants. While traditional depression treatments often focus on altering serotonin or norepinephrine levels, REL-1017 targets the NMDA receptor, a part of the brain's glutamate system. This new mechanism offers the potential for faster relief from depressive symptoms, which is exciting for researchers and patients alike. Additionally, REL-1017 is administered orally, making it convenient for daily use alongside existing antidepressants.

What evidence suggests that REL-1017 might be an effective treatment for depression?

Research has shown that REL-1017, which participants in this trial may receive, might help treat Major Depressive Disorder (MDD) when combined with other antidepressants. One study found that 26.6% of patients felt much better by Day 7, increasing to 51% by the end of the first month. After six months, 63.4% of patients demonstrated a strong and lasting improvement. REL-1017 also appeared safe and effective for patients who did not respond well to other treatments. Overall, these findings suggest that REL-1017 could be a promising option for people dealing with depression. ^{1 3 4 6 7}

Who Is on the Research Team?

Paul Greene, PhD

Principal Investigator

Relmada Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder (MDD) who are currently experiencing a depressive episode and haven't had adequate relief from 1 to 3 antidepressant treatments. Participants must be on stable first-line antidepressant therapy. It's not for those with severe substance abuse, recent opioid use, history of certain brain stimulation therapies, suicidal behavior in the past year, bipolar disorder, psychosis or prior NMDAR antagonist treatment.

Inclusion Criteria

You have been diagnosed with Major Depressive Disorder

Are you currently depressed?

Have previous depression medications not worked for you?

Exclusion Criteria

Have you been diagnosed with a mental illness other than depression?

Have you taken ketamine or esketamine for your depression in the past?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REL-1017 or placebo once daily for 28 days as an adjunctive treatment to their current antidepressant therapy

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REL-1017

Trial Overview The study tests REL-1017 as an add-on treatment for MDD against a placebo. Participants will continue their regular antidepressants and receive either REL-1017 or a placebo daily. The trial aims to see if adding REL-1017 improves depression symptoms more than just the standard treatment alone.

How Is the Trial Designed?

Group I: REL-1017 25 mg Experimental Treatment 1 Intervention

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)

Group II: Placebo Placebo Group 1 Intervention

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).

Who Is Running the Clinical Trial?

Levomecor Inc.

Lead Sponsor

Relmada Therapeutics, Inc.

Lead Sponsor

Trials

9

Recruited

1,500+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38917366/

Efficacy and Safety of Esmethadone (REL-1017) in ... Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04688164

A Study to Assess the Efficacy and Safety of REL-1017 as ... Response rate is defined as an improvement ≥50% compared with total Baseline MADRS10 score.

3. psychiatrist.com psychiatrist.com/jcp/esmethadone-rel-1017-major-depressive-disorder-antidepressant-tachyphylaxis-post-hoc-analysis-phase-3-rct/

Esmethadone (REL-1017) in Patients With Major ... Esmethadone may be a potentially safe and effective adjunctive treatment for patients with MDD and antidepressant tachyphylaxis.

4. relmada.com relmada.com/for-investors/news/detail/285/relmada-therapeutics-announces-efficacy-and-safety-results

Relmada Therapeutics Announces Efficacy and Safety ... When treated with REL-1017, 26.6% of de novo patients achieved clinical response by Day 7, 51.0% by Month 1, 60.7% by Month 3, 63.4% by Month 6, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04855747

A Study to Assess the Efficacy and Safety of REL-1017 as ... 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04855760

Safety of REL-1017 for Major Depressive Disorder This was a 1-year, multicenter, open-label, long-term study to assess the safety of REL-1017 once daily (QD) as monotherapy or as adjunctive treatment of Major ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36821775/

Subanalysis of Subjective Cognitive Measures From a ... In a Phase 2a clinical trial, REL-1017 improved subjective measures of cognitive impairment, in addition to improving total MADRS and SDQ scores.