NMRA-335140 for Depression

Recruiting at 109 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Neumora Therapeutics, Inc.

Disqualifiers: Personality disorder, Bipolar, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 52 weeks

650 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety and effectiveness of NMRA-335140 for individuals with major depressive disorder (MDD). It serves as an extension study for participants who have completed a prior study with this medication. Participants will take a daily tablet for 52 weeks. Ideal candidates are those who have finished a previous NMRA-335140 study for MDD without significant side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment for MDD.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you must comply with medication restrictions from the parent study. It's best to discuss your current medications with the study team to understand any specific requirements.

Is there any evidence suggesting that NMRA-335140 is likely to be safe for humans?

Research has shown that NMRA-335140 has been tested for safety in people with major depressive disorder. In earlier studies, this treatment was generally well-tolerated, meaning most participants did not experience serious side effects.

One study compared NMRA-335140 to a placebo (a pill with no active ingredients). The results indicated that participants taking NMRA-335140 did not experience more side effects than those taking the placebo. This finding suggests NMRA-335140 is safe for most people.

Some individuals might experience mild side effects, but these are usually not serious. This information comes from research involving many participants, providing strong evidence that NMRA-335140 is safe to use. ^{1 2 3 4 5}

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

Most treatments for depression, like SSRIs or SNRIs, work by altering neurotransmitter levels in the brain. But NMRA-335140 is different because it targets a novel pathway, potentially offering relief to patients who haven't responded to existing medications. This treatment is also administered as a convenient, once-daily tablet, which could improve patient adherence. Researchers are excited about its potential to provide a new option for those with treatment-resistant depression.

What evidence suggests that NMRA-335140 might be an effective treatment for major depressive disorder?

Research has shown that NMRA-335140, also known as navacaprant, might help treat major depressive disorder (MDD). Early studies suggest it could alleviate depression, inability to feel pleasure, and anxiety. However, one study found it did not significantly reduce depression symptoms compared to a placebo, indicating mixed results. While initial findings are promising, further research is needed to confirm its effectiveness for MDD. Participants in this trial will receive NMRA-335140 at a dose of 80 mg once daily during a 52-week treatment period. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for people who have major depressive disorder and completed a previous NMRA-335140 study. They must have signed an informed consent form, agree to follow medication restrictions, and comply with contraception requirements from the earlier study.

Inclusion Criteria

You have consented to participation in this study via the completion of an ICF.

You are willing to follow the associated medication/therapy rules outlined in the document.

You have successfully concluded a Phase 3 MDD study (NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303) as dictated by the provisions of the source protocol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NMRA-335140 at a dose of 80 mg once daily during a 52-week treatment period

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Open-label extension

Participants continue to receive NMRA-335140 to assess long-term safety and effectiveness

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NMRA-335140

Trial Overview The trial is testing the safety and effectiveness of a drug called NMRA-335140 over 52 weeks in participants with major depressive disorder who previously took part in related studies.

How Is the Trial Designed?

Group I: NMRA-335140 80 milligrams (mg) once daily (QD) Experimental Treatment 1 Intervention

Participants will receive a NMRA-335140 tablet at a dose of 80 mg once daily (QD) during a 52-week treatment period.

Who Is Running the Clinical Trial?

Neumora Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

2,100+

Published Research Related to This Trial

Current antidepressant treatments for major depressive disorder (MDD) and bipolar disorder (BD) often have delayed effects and limited efficacy, primarily targeting monoamine systems, while novel glutamate receptor modulators show promise for faster-acting antidepressant effects.

Ketamine, a non-competitive NMDA receptor antagonist, has demonstrated rapid and robust antidepressant effects, leading to the exploration of other NMDA antagonists and glutamate modulators, which may offer similar or improved therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New targets for rapid antidepressant action. Machado-Vieira, R., Henter, ID., Zarate, CA.[2022]

In a 52-week study involving 813 patients with major depressive disorder who had inadequate responses to previous treatments, dexmecamylamine was found to be generally safe and tolerable when used alongside SSRIs/SNRIs.

While 82.4% of patients on dexmecamylamine experienced adverse events, the most common were mild, such as constipation and dizziness, and overall safety profiles were consistent with earlier studies, indicating it may be a viable adjunct treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of dexmecamylamine (TC-5214) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to antidepressant therapy: results of a long-term study. Tummala, R., Desai, D., Szamosi, J., et al.[2022]

The combination of brexpiprazole and fluoxetine significantly alters amino acid levels in the brain, which may contribute to its antidepressant effects, as shown in a study measuring tissue levels after single and repeated doses.

Specifically, the combination increased GABA levels and affected the D-serine/L-serine and glycine/L-serine ratios in various brain regions, indicating a potential mechanism of action related to NMDAR neurotransmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in amino acid levels in mouse brain regions after adjunctive treatment of brexpiprazole with fluoxetine: comparison with (R)-ketamine. Ma, M., Ren, Q., Fujita, Y., et al.[2018]

Ketamine has shown a unique fast-acting neuroprotective and antidepressant effect by targeting the glutamatergic system, suggesting that glutamate plays a significant role in treating major depression.

Emerging treatments, including NMDA receptor antagonists and AMPA agonists, have demonstrated the ability to promote new synaptic connections and reverse stress-induced neuronal changes, indicating a promising direction for future antidepressant drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of calcium, glutamate and NMDA in major depression and therapeutic application. Deutschenbaur, L., Beck, J., Kiyhankhadiv, A., et al.[2015]

In two Phase III studies involving 614 patients with major depressive disorder, TC-5214 (dexmecamylamine) did not show significant antidepressant effects compared to placebo, as measured by the Montgomery Åsberg Depression Rating Scale (MADRS).

While TC-5214 was generally well tolerated, the most common side effects reported were constipation and headache, indicating that while it may not be effective, it does not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant. Vieta, E., Thase, ME., Naber, D., et al.[2022]

Prolonged treatment with various antidepressants and the mGlu5 negative allosteric modulator MTEP resulted in significant increases in mGlu5 receptor binding in the rat brain, suggesting enhanced receptor availability.

The study indicates that adaptive up-regulation of mGlu5 receptors may be a common response to different antidepressant treatments, which could play a role in their therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged administration of antidepressant drugs leads to increased binding of [(3)H]MPEP to mGlu5 receptors. Nowak, G., Pomierny-Chamioło, L., Siwek, A., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04221230

Study in Major Depressive Disorder With NMRA-335140 ... A proof of concept (POC) study evaluating the impact of NMRA-335140 (BTRX-335140) relative to placebo on symptoms of major depressive disorder (MDD) in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40199329/

A Randomized, Double-Blind Phase 2 Clinical Trial This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid ...

3. ir.neumoratx.com ir.neumoratx.com/news-releases/news-release-details/neumora-therapeutics-reports-data-koastal-1-study-navacaprant

Neumora Therapeutics Reports Data from KOASTAL-1 Study ... Study did not demonstrate statistically significant improvement on primary endpoint of reduction in depressive symptoms as measured by MADRS ...

4. neumoratx.com neumoratx.com/wp-content/uploads/2024/08/ACNP23_Ph2_Poster_Final.pdf

Navacaprant (NMRA-140), A Novel and Highly Selective ... results from preclinical studies support its potential to modulate depression, anhedonia, and anxiety6 (Figure 1). Ȳ Navacaprant (NMRA-140, BTRX-335140) is a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06429722

NCT06429722 | To Evaluate the Effects of NMRA-335140 ... This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults ...