BHV-7000 for Depression

Enrolling by invitation at 68 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Biohaven Therapeutics Ltd.

Disqualifiers: Medical condition, Non-compliance, Risk to others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment called BHV-7000 for individuals with Major Depressive Disorder (MDD). The researchers aim to determine how people with MDD respond to the treatment over an extended period. Ideal participants are those who have previously participated in related studies and consistently followed study procedures. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

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

Earlier studies have shown that BHV-7000 is safe and well-tolerated in people. Research indicates that taking up to 120 mg daily for 15 days did not cause severe side effects that would prevent continuation of the treatment. This dose exceeds what is typically used in current studies, suggesting a good safety margin. Additionally, earlier studies found no negative effects on the brain and nervous system, which are often seen with similar drugs. This is encouraging for those considering joining this trial for depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for depression, which often involve SSRIs like fluoxetine or SNRIs such as venlafaxine, BHV-7000 works differently, targeting specific receptors in the brain that are thought to play a role in mood regulation. Researchers are excited about BHV-7000 because it may offer faster relief from depressive symptoms compared to traditional antidepressants, which usually take weeks to show effects. This new mechanism of action could potentially lead to more effective and quicker treatment options for patients struggling with depression.

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

Research has shown that BHV-7000, the investigational treatment in this trial, activates certain potassium channels in the brain, known as Kv7.2/7.3. This action may stabilize brain activity and potentially improve depression symptoms. Previous studies found BHV-7000 to be safe and well-tolerated by participants. However, it did not show significant improvement in a trial for bipolar disorder, a different condition. There remains hope for its effectiveness in treating depression, particularly because it operates differently from many current treatments. Further research is needed to confirm its effectiveness for major depressive disorder. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals who have completed the initial phase of parent studies on Major Depressive Disorder (MDD). Women of childbearing potential must not be pregnant, breastfeeding, or lactating and should test negative for pregnancy to participate.

Inclusion Criteria

I have finished the initial phase of a previous study.

I am not breastfeeding or planning to during the study.

I am a woman of childbearing potential and my pregnancy test before starting the trial is negative.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BHV-7000 to evaluate long-term safety and tolerability

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BHV-7000

Trial Overview The study is focused on assessing the long-term safety and tolerability of a medication called BHV-7000 in people with MDD. It aims to understand how well patients can handle this treatment over an extended period.

How Is the Trial Designed?

Group I: BHV-7000 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Biohaven Therapeutics Ltd.

Lead Sponsor

Trials

13

Recruited

4,800+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 ...