BHV-7000 for Depression

Recruiting at 4 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Biohaven Therapeutics Ltd.

Must not be taking: Psychotropics

Disqualifiers: Bipolar, Schizophrenia, Neuropsychiatric, others

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

3 Power Preferred Clinics 3 of this trial's clinics are considered top 20 on Power

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BHV-7000 to determine its effectiveness and safety for people with Major Depressive Disorder (MDD). Participants will receive either BHV-7000 or a placebo (a pill with no active medicine) to compare results. Those experiencing moderate to severe depression for at least two months and willing to stop other depression medications may be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all medications used to treat depression before joining the study.

Is there any evidence suggesting that BHV-7000 is likely to be safe for humans?

Research has shown that BHV-7000 is generally safe and well-tolerated in people. In earlier studies, participants took up to 120 mg of BHV-7000 daily for 15 days without serious side effects. This dosage exceeds the amount tested for depression, and no severe reactions required stopping the medication.

Previous studies also found that BHV-7000 did not cause side effects on the brain and nerves, which are common with similar drugs. This finding is positive because it means fewer issues like dizziness or confusion.

Overall, the evidence suggests that BHV-7000 is safe for people and could be a promising treatment for depression. ^{1 2 3 4 5}

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

BHV-7000 is unique because it potentially offers a new approach to treating depression by targeting different pathways in the brain compared to existing treatments. Most current antidepressants, like SSRIs and SNRIs, work by increasing levels of serotonin or norepinephrine. However, BHV-7000 is believed to work on the glutamate system, which could provide faster relief of symptoms for some patients. Researchers are excited because this novel mechanism could offer hope for those who haven't responded well to traditional treatments.

What evidence suggests that BHV-7000 might be an effective treatment for MDD?

Research suggests that BHV-7000, which participants in this trial may receive, could be promising for treating Major Depressive Disorder (MDD) due to its mechanism of action. It targets specific potassium channels in the brain, helping to calm overactive brain cells. Although a previous trial for bipolar disorder did not show significant benefits, BHV-7000 was found to be safe and well-tolerated. Early safety studies in healthy adults demonstrated it was well-tolerated without serious side effects. This indicates potential effectiveness for MDD, but further research is needed to confirm its benefits. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with moderate to severe depression lasting at least 2 months. Participants must have a BMI between 18 and 35, agree to stop all psychotropic meds before the study, and not be pregnant or planning pregnancy. Those with bipolar disorder, schizophrenia, or on multiple depression medications are excluded.

Inclusion Criteria

At the beginning of the study, you would need to have a negative test for cannabis and not use any cannabis during the study. Would you be okay with that?

Have you been experiencing symptoms of depression for over 2 months but less than 2 years?

Have you felt at least 3 of the following things recently? Feeling sad; low energy or feeling tired; hopelessness or putting yourself down; not being interested in things that you usually enjoy such as hobbies or activities, or friends and family; difficulty concentrating or focusing on things; appetite changes like pushing yourself to eat orovereating; difficulty falling or staying asleep, or oversleeping?

Exclusion Criteria

Have you been diagnosed with Autism Spectrum Disorder?

Have you been diagnosed with Parkinson's Disease?

Have you been diagnosed with Alzheimer's Disease?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BHV-7000 or placebo for 6 weeks to evaluate efficacy and safety in Major Depressive Disorder

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BHV-7000

Trial Overview The trial is testing BHV-7000's effectiveness and safety in treating Major Depressive Disorder (MDD). Participants will either receive BHV-7000 or a placebo to compare outcomes.

How Is the Trial Designed?

Group I: BHV-7000 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Biohaven Therapeutics Ltd.

Lead Sponsor

Trials

13

Recruited

4,800+

Published Research Related to This Trial

Inhibiting the pro-apoptotic protein Bid in mice using pharmacological antagonists significantly reduced behaviors associated with depression in various rodent models, indicating a potential therapeutic target for mood disorders.

The study found that both Bid inhibition and the selective serotonin reuptake inhibitor citalopram improved depressive behaviors, suggesting that manipulating apoptotic pathways could be a promising strategy for developing new treatments for mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressants. Malkesman, O., Austin, DR., Tragon, T., et al.[2021]

Chronic stress reduces the production of brain-derived neurotrophic factor (BDNF) in the hippocampus, which is linked to hippocampal atrophy and depressive disorders.

Blood levels of BDNF decrease in depressed patients, and treatments like selective serotonin reuptake inhibitors can help restore these levels, suggesting that BDNF may serve as a potential biomarker for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brain-derived neurotrophic factor (BDNF) and mood disorder]. Yoshimura, R., Ikenouchi-Sugita, A., Hori, H., et al.[2022]

Banxia-houpo decoction (BXHPD) effectively reduces depressive-like behavior in mice subjected to chronic unpredicted mild stress (CUMS), indicating its potential as a safe antidepressant with limited side effects.

BXHPD promotes the polarization of microglia towards the anti-inflammatory M2 phenotype through the TrkA/Akt signaling pathway, and this effect can be blocked by a TrkA inhibitor, highlighting the mechanism of action behind its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of Banxia-houpo decoction on CUMS-induced depression by promoting M2 microglia polarization via TrkA/Akt signalling. Liu, L., Zhang, R., Chen, C., et al.[2023]

HBK-15, a novel 5-HT1A and 5-HT7 receptor antagonist, demonstrated antidepressant and anxiolytic effects in a mouse model of chronic stress, showing potential to alleviate depressive and anxiety-like behaviors while enhancing memory.

The pharmacokinetic profile of HBK-15 revealed rapid absorption and significant brain penetration, suggesting its effectiveness in targeting the central nervous system, which may be beneficial for treating depression with cognitive dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HBK-15 protects mice from stress-induced behavioral disturbances and changes in corticosterone, BDNF, and NGF levels. Pytka, K., Głuch-Lutwin, M., Kotańska, M., et al.[2018]

AVN-101 is a multi-targeted drug candidate that acts primarily as a potent 5-HT7 receptor antagonist, showing good oral bioavailability and the ability to cross the blood-brain barrier, making it a promising treatment for CNS disorders.

In Phase I clinical trials, AVN-101 was well tolerated at doses up to 20 mg daily, with low toxicity and no significant effects on plasma biochemistry or heart rhythm, indicating a favorable safety profile for further testing in conditions like Alzheimer's disease and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. Ivachtchenko, AV., Lavrovsky, Y., Okun, I.[2019]

Chemical modifications of compound 1 (DR4004) led to the development of new compounds (7-10) that maintained high affinity and selectivity for the 5-HT(7) receptor while improving metabolic stability.

Compound 10 (DR4485) demonstrated oral bioavailability, making it a promising candidate for further research into the therapeutic potential of 5-HT(7) antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New tetrahydrobenzindoles as potent and selective 5-HT(7) antagonists with increased In vitro metabolic stability. Kikuchi, C., Suzuki, H., Hiranuma, T., et al.[2019]

Banxia-Houpo-Tang (BHT) shows similar efficacy to standard antidepressants for treating depression, based on a meta-analysis of 15 randomized controlled trials involving 1,714 participants.

BHT alone has a lower risk of adverse events compared to antidepressants, although combining BHT with antidepressants does not increase this risk, indicating it may be a safer adjunct treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Banxia-Houpo-Tang (Banha-Hubak-Tang) for depression: A systematic review and meta-analysis. Kim, DW., Kwon, HW., Kim, SH.[2023]

The compound N-2'-chlorobiphenylylmethyl 2-methoxyphenylpiperazinylpentanamide (1-8) was identified as a highly selective antagonist of the 5-HT7 receptor, showing a strong binding affinity and potential for treating depression and neuropathic pain.

In animal tests, this novel antagonist demonstrated antidepressant effects at a dose of 25 mg/kg, exhibiting a U-shaped dose-response curve typical of effective 5-HT7R antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression. Kim, Y., Tae, J., Lee, K., et al.[2014]

In a rat model of post-stroke depression, injecting a BDNF gene lentiviral vector into the hippocampus significantly increased BDNF expression, which is typically reduced in depression.

The increased BDNF levels were associated with improved behaviors, such as higher sucrose consumption and increased movement in open field tests, indicating that BDNF overexpression may help alleviate depression-like symptoms after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression. Chen, HH., Zhang, N., Li, WY., et al.[2020]

The selective 5-HT7 receptor antagonist SB 269970 demonstrated specific antianxiety effects in multiple behavioral tests in rats and mice, indicating its potential as an anxiolytic treatment.

SB 269970 also showed antidepressant-like activity in mice without affecting their locomotor activity, suggesting it may be a safer option with fewer side effects compared to standard drugs like diazepam and imipramine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression. Wesołowska, A., Nikiforuk, A., Stachowicz, K., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06419608?cond=Major%20depressive%20disorder&aggFilters=status:not%20rec%20ava&viewType=Table&rank=8

Efficacy and Safety Study of BHV-7000 Monotherapy in ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2. ir.biohaven.com ir.biohaven.com/news-releases/news-release-details/biohaven-presents-new-data-bhv-7000-once-daily-extended-release

Biohaven Presents New Data with BHV-7000 Once-Daily ... Reported expanded safety results from BHV-7000 Phase 1 multiple ascending dose studies, including the once-daily extended-release formulation being ...

3. aesnet.org aesnet.org/abstractslisting/a-first-in-human-phase-1-study-evaluating-the-safety-and-tolerability-of-bhv-7000-a-novel-selective-kv7-2-7-3-potassium-channel-activator-in-healthy-adults

Abstracts - American Epilepsy Society A First in Human Phase 1 Study Evaluating the Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3 Potassium Channel Activator ...

4. psychiatrictimes.com psychiatrictimes.com/view/bhv-7000-for-bipolar-disorder-fails-in-phase-2-3-trial

BHV-7000 for Bipolar Disorder Fails in Phase 2/3 Trial BHV-7000 failed to achieve statistical significance in a bipolar trial but was safe and well-tolerated, with no serious adverse events.

5. ctv.veeva.com ctv.veeva.com/study/long-term-safety-study-of-bhv-7000-in-participants-with-major-depressive-disorder-mdd

Long-term Safety Study of BHV-7000 in Participants With ... The purpose of this study is to evaluate the long-term safety and tolerability of BHV-7000, in participants with Major Depressive Disorder (MDD) ...

6. biohaven.com biohaven.com/wp-content/uploads/ACNP-2024-poster-BHV-7000-preclinical-antidepressant-and-impulse-control.pdf

ACNP-2024-poster-BHV-7000-preclinical-antidepressant- ... – BHV-7000 was safe and well tolerated in phase 1 studies, without central nervous system adverse effects typical of antiseizure medications8. OBJECTIVE. • To ...