NMRA-335140 for Depression

Recruiting at 5 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Neumora Therapeutics, Inc.

Disqualifiers: Personality disorder, Bipolar, Schizophrenia, others

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: 6 weeks

332 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, NMRA-335140, to determine its effectiveness in reducing symptoms of Major Depressive Disorder (MDD). Participants will receive either the experimental treatment or a placebo (a non-active pill) for six weeks. The trial aims to assess whether NMRA-335140 improves depression symptoms more effectively than the placebo. Individuals who have experienced depression symptoms for more than four weeks but less than a year, and have not had multiple failed antidepressant treatments, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for depression.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 treating depression. In earlier studies with adults who have major depressive disorder (MDD), the treatment was generally well-tolerated. Specifically, one study found that most patients did not experience severe side effects. The most common issues were mild, such as headaches and nausea, similar to those of other medications.

This current study is in phase three, indicating that earlier phases have already assessed safety and shown positive results. Phase three studies are larger and focus on confirming a treatment's safety and effectiveness. If NMRA-335140 is approved for other uses, it suggests some level of safety, but previous studies primarily support its use in depression. Always consult a healthcare professional about any concerns before joining a trial. ^{1 2 3 4 5}

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

Most treatments for depression, like SSRIs and SNRIs, work by altering neurotransmitter levels in the brain to improve mood over time. However, NMRA-335140 is unique because it targets a different mechanism that could offer faster relief from depressive symptoms. Researchers are excited about this drug's potential to provide quicker and possibly more effective results compared to traditional antidepressants. This could be a game-changer for people struggling with depression who need faster symptom relief.

What evidence suggests that NMRA-335140 might be an effective treatment for depression?

This trial will compare NMRA-335140, also known as BTRX-335140, with a placebo to determine its potential in treating depression by affecting certain brain pathways. Research has shown mixed results: in some cases, NMRA-335140 did not significantly reduce depression symptoms compared to a placebo, but early studies suggested it might help with depression and anxiety. This treatment specifically targets kappa opioid receptors, which play a role in mood regulation. While strong agreement is lacking, ongoing research, including this trial, aims to determine its effectiveness for major depressive disorder. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder (MDD) confirmed by a clinical interview, experiencing symptoms for more than 4 weeks but less than 12 months. They must have moderate to severe depression scores and stable symptoms between screening and baseline. Details about specific exclusions are not provided.

Exclusion Criteria

Have you been diagnosed with Schizophrenia?

Have you consistenly felt depressed for more than 12 months?

Have you been diagnosed with Bipolar Disorder?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either NMRA-335140 or placebo for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with NMRA-335140 long-term

What Are the Treatments Tested in This Trial?

Interventions

• NMRA-335140
• Placebo

Trial Overview The study tests the effects of NMRA-335140 compared to a placebo on depression symptoms over six weeks. Participants will be randomly assigned to receive either the experimental drug or placebo without knowing which one they're getting (double-blind). There's also an optional extension study afterwards.

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)

Group II: Placebo Placebo Group 1 Intervention

Placebo participants will receive matching placebo tablet once daily.

Who Is Running the Clinical Trial?

Neumora Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

2,100+

Published Research Related to This Trial

Ketamine, an NMDA antagonist, has shown rapid improvement in depressive symptoms for patients who do not respond to traditional antidepressants, with effects lasting several days after a low-dose infusion.

A pilot study indicated that a higher-dose, 96-hour infusion of ketamine, combined with clonidine to reduce side effects, resulted in about 40% of subjects maintaining a good response for 8 weeks, highlighting the need for further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. Farber, NB.[2019]

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]

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]

A single intravenous infusion of ketamine significantly reduces depressive symptoms in patients with major depressive disorder (MDD) and bipolar depression (BD), showing effects as early as 40 minutes and peaking at day 1, with a strong effect size (Hedges' g = -1.00).

Non-ketamine NMDAR antagonists also show efficacy, but their effects are less pronounced and only significant from days 5-8, indicating that ketamine may offer a faster and more robust treatment option for refractory depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Kishimoto, T., Chawla, JM., Hagi, K., et al.[2022]

NMDA receptor antagonists may help reduce neurotoxic damage in various neurological diseases, suggesting a potential therapeutic role in treating these conditions.

The review highlights clinically tolerated NMDA receptor antagonists that have been used for other medical conditions and can inhibit NMDA receptor activity through mechanisms like open-channel block or redox modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for clinically tolerated NMDA antagonists: open-channel blockers and alternative redox states of nitric oxide. Lipton, SA.[2022]

NMDA receptor antagonists, particularly ketamine, have shown promising antidepressant effects in clinical studies, making them a focus for developing new depression treatments.

While ketamine demonstrates rapid antidepressant action, its clinical use is limited due to adverse effects, highlighting the need for safer alternatives that can provide similar benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational NMDA receptor modulators for depression. Szewczyk, B., Pałucha-Poniewiera, A., Poleszak, E., et al.[2013]

Recent research highlights the potential of NMDA receptor antagonists, like ketamine and esketamine, as effective treatments for major depressive disorder (MDD), especially for patients who do not respond to traditional antidepressants.

Esketamine's recent FDA approval marks a significant advancement in antidepressant therapy, but further investigation is needed to fully understand the mechanisms and address safety concerns associated with these NMDA receptor-targeting drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on NMDA antagonists in depression. Pochwat, B., Nowak, G., Szewczyk, B.[2020]

A new series of benzopolycyclic amines were developed as NMDA receptor antagonists, showing increased activity compared to earlier analogues.

One of the compounds demonstrated a lower IC50 value than memantine, a drug approved for Alzheimer's, indicating it may be a more potent option for treating related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel benzopolycyclic amines with NMDA receptor antagonist activity. Valverde, E., Sureda, FX., Vázquez, S.[2014]

In a study involving 117 elderly patients with major depressive disorder, sodium benzoate showed significant improvements in perceived stress and cognitive function compared to placebo, suggesting its potential as a novel treatment for late-life depression.

While sertraline effectively reduced self-reported depressive symptoms, it was associated with a higher risk of increasing low-density lipoprotein levels and had a higher dropout rate compared to sodium benzoate, indicating that sodium benzoate may be a safer and more tolerable option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial. Lin, CH., Wang, SH., Lane, HY.[2022]

In a randomized, double-blind trial involving 31 adult outpatients with major depressive disorder, memantine did not show significant improvement in depression symptoms compared to placebo after 8 weeks of treatment.

Despite a high completion rate of 84%, the study concluded that memantine lacks substantial efficacy as an augmentation treatment for patients who did not respond well to conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. Smith, EG., Deligiannidis, KM., Ulbricht, CM., et al.[2021]

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 ...