NBI-1065845 for Depression

(SAVITRI Trial)

Recruiting at 42 trial locations

Overseen By Neurocrine Medical Information Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neurocrine Biosciences

Must be taking: Antidepressants

Disqualifiers: Pregnancy, Neurological abnormalities, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

183 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called NBI-1065845 to see if it can help people with Major Depressive Disorder (MDD) feel better. The goal is to find out if NBI-1065845 can reduce symptoms of depression.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants currently on antidepressants must have been taking them for at least 8 weeks before the trial.

What data supports the effectiveness of the drug NBI-1065845 for depression?

The research on vilazodone, a drug used for major depressive disorder, shows significant improvement in depression severity compared to a placebo, suggesting that similar treatments can be effective. Additionally, venlafaxine, another antidepressant, demonstrated significant improvement in depression scores, indicating that drugs with similar mechanisms may be beneficial. ^{1 2 3 4 5}

Is NBI-1065845 safe for humans?

The study on NSI-189, a similar compound, showed it was generally well tolerated with no serious side effects in patients with depression. ^{6 7 8 9 10}

How is the drug NBI-1065845 different from other depression treatments?

NBI-1065845, also known as NSI-189, is unique because it is a neurogenic compound that works independently of the traditional monoamine reuptake pathways (the usual way many antidepressants work). It aims to stimulate brain cell growth and improve cognitive function, offering a novel approach compared to standard antidepressants. ^{6 11 12 13 14}

Research Team

Clinical Development Lead

Principal Investigator

Neurocrine Biosciences

Eligibility Criteria

Adults aged 18-65 with Major Depressive Disorder (MDD) who haven't had enough improvement from previous antidepressant treatments can join. They must be on a stable depression medication for at least 8 weeks or have taken it for that long in their current episode. Pregnant or breastfeeding individuals, those with unstable health conditions, certain psychiatric disorders other than MDD, or a history of substance abuse cannot participate.

Inclusion Criteria

The subject has completed written informed consent.

Subject is currently on stable pharmacological treatment for depression.

The participant has completed written informed consent.

Exclusion Criteria

Participant is pregnant or breastfeeding or plans to become pregnant during the study.

Participant has an unstable medical condition or unstable chronic disease.

In the Investigator's opinion, the participant is not capable of adhering to the protocol requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or NBI-1065845 (low or high dose) orally once a day

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NBI-1065845
• Placebo

Trial Overview The trial is testing the effectiveness of NBI-1065845 versus a placebo in improving symptoms of depression in adults with MDD. Participants will either receive the experimental drug NBI-1065845 or a placebo to compare outcomes between the two groups.

Participant Groups

Group I: NBI-1065845 Low Dose Experimental Treatment 1 Intervention

Participants will receive low-dose NBI-1065845 orally once a day.

Group II: NBI-1065845 High Dose Experimental Treatment 1 Intervention

Participants will receive high-dose NBI-1065845 orally once a day.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive placebo orally once a day.

Who Is Running the Clinical Trial?

Neurocrine Biosciences

Lead Sponsor

Trials

78

Recruited

6,600+

Kyle W. Gano

Neurocrine Biosciences

Chief Executive Officer since 2024

PhD in Pharmacology

Dr. Sanjay Keswani

Neurocrine Biosciences

Chief Medical Officer

MD

Findings from Research

NSI-189, a neurogenic compound, was well tolerated in a Phase 1B study with 24 patients suffering from major depressive disorder, showing no serious adverse effects across multiple dosing regimens.

The treatment demonstrated promising efficacy, with significant reductions in depressive and cognitive symptoms measured by various scales, indicating potential as a new treatment option for MDD, although the study's small sample size is a limitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Fava, M., Johe, K., Ereshefsky, L., et al.[2022]

Aripiprazole augmentation for major depressive disorder (MDD) shows a remission rate of approximately 33% over long-term treatment (≥6 months), suggesting it can be an effective strategy for patients who do not respond to standard treatments.

Lower doses of aripiprazole (2-5 mg) are associated with fewer adverse effects, such as weight gain and akathisia, compared to higher doses (≥5 mg), making it a safer option for long-term management of MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis. Seshadri, A., Wermers, ME., Habermann, TJ., et al.[2021]

In a 12-week trial with 220 participants, NSI-189 at a 40 mg daily dose showed a significant reduction in depression symptoms on the Symptoms of Depression Questionnaire (SDQ) and Cognitive and Physical Functioning Scale (CPFQ) compared to placebo, suggesting potential efficacy in treating major depressive disorder.

Both doses of NSI-189 were well tolerated, indicating a favorable safety profile, and the findings support further investigation into its antidepressant and cognitive-enhancing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. Papakostas, GI., Johe, K., Hand, H., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Categorical improvements in disease severity in patients with major depressive disorder treated with vilazodone: post hoc analysis of four randomized, placebo-controlled trials. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Rethinking the medication management of major depression. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Differentiation between major and minor depression. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. [2011]

5. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of venlafaxine for the treatment of major depression. [2015]

6. England pubmed.ncbi.nlm.nih.gov

A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. [2022]

7. Denmark pubmed.ncbi.nlm.nih.gov

Achieving gains beyond response. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Escitalopram in the long-term treatment of major depressive disorder in elderly patients. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of escitalopram in treatment of severe depression in Chinese population. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Transient inactivation of the infralimbic cortex induces antidepressant-like effects in the rat. [2013]

12. England pubmed.ncbi.nlm.nih.gov

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. [2021]

13. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets? [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Advances in the treatment of depression. [2022]