JNJ-89495120 for Depression

(Moonlight-1 Trial)

Overseen By Study Contact

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Ketamine, Esketamine

Disqualifiers: Bipolar, Psychotic disorders, Substance use, others

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

1 Power Preferred Clinic 1 of this trial's clinic is considered top 20 on Power

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

124 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate how well JNJ-89495120 works (anti-depressant effects) and how well it is tolerated as compared to placebo on reducing the symptoms of depression in participants with major depressive disorder (MDD).

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.

What data supports the effectiveness of the drug JNJ-89495120 for treating depression?

Research on venlafaxine, a similar drug, shows it can help some people with treatment-resistant depression, with about a third of patients experiencing improvement. This suggests that drugs with similar mechanisms might also be effective for depression. ^{1 2 3 4 5}

How does the drug JNJ-89495120 work differently for depression?

JNJ-89495120 is unique because it is a triple reuptake inhibitor, meaning it blocks the reabsorption of three key neurotransmitters (chemical messengers in the brain): serotonin, norepinephrine, and dopamine. This multi-target approach may offer advantages over traditional treatments that typically focus on just one neurotransmitter. ^{6 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults who were first diagnosed with depression before age 55, are currently in a depressive episode lasting 2-24 months, and have had up to two treatments for this episode. They must have experienced at least one prior MDD episode, have a BMI of 18-35 kg/m^2, and not suffer from bipolar disorder, psychotic disorders, certain personality disorders or PTSD within the last three years.

Inclusion Criteria

Have you taken an antidepressant before?

Were you first diagnosed with depression before the age of 55?

Have you had a previous depression episode prior to your current one?

Exclusion Criteria

Have you taken more than 2 treatments for your depression?

Have you ever been treated with with vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), or ketamine/esketamine?

Have you ever been diagnosed with bipolar disorder, schizophrenia, borderline personality disorder, antisocial personality disorder, or obsessive-compulsive disorder?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JNJ-89495120 or placebo during the double-blind treatment phase in Period 1 and Period 2

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-89495120

Trial Overview The study tests JNJ-89495120's effectiveness and tolerability against a placebo in reducing symptoms of major depressive disorder (MDD). Participants will either receive the experimental drug or an inactive substance without knowing which one they're getting.

Participant Groups

Group I: Arm 2: JNJ-89495120 Dose A and Dose B Experimental Treatment 1 Intervention

Participants will receive JNJ-89495120 dose A in Period 1 followed by JNJ-89495120 dose B in Period 2 during the DB treatment phase of the study.

Group II: Arm 1: JNJ-89495120 Dose A Experimental Treatment 1 Intervention

Participants will receive JNJ-89495120 dose A during the double-blind (DB) treatment phase in Period 1 and Period 2 of the study.

Group III: Arm 3: Placebo Group Placebo Group 1 Intervention

Participants will receive placebo matched to JNJ-89495120 during the DB treatment phase in Period 1 and Period 2 of the study.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

In a study of 84 patients with treatment-resistant unipolar depression, venlafaxine showed effectiveness, with about one-third of patients achieving full or partial response after 12 weeks of treatment.

Approximately 46% of those who responded to venlafaxine maintained their improvement for at least 3 months, indicating that it can provide sustained benefits for some individuals with severe depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venlafaxine for treatment-resistant unipolar depression. Nierenberg, AA., Feighner, JP., Rudolph, R., et al.[2015]

Depression affects a significant portion of the population, with 6.6% of Americans experiencing a depressive episode annually, and 60-70% of patients not fully responding to standard antidepressant treatments.

Given the high rates of treatment-resistant depression and the associated risk of suicide, optimizing treatment through various modalities such as pharmacotherapy, electroconvulsive therapy, and psychotherapy is crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging antidepressants to treat major depressive disorder. Block, SG., Nemeroff, CB.[2016]

Venlafaxine is more effective than selective serotonin reuptake inhibitors (SSRIs) in treating major depression, with a greater likelihood of achieving a therapeutic response and remission, as shown by a meta-analysis of various trials.

In patients with treatment-resistant depression, venlafaxine demonstrated superior efficacy compared to alternative antidepressants, and it also significantly reduced the risk of relapse when used long-term after a major depressive episode.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. Bauer, M., Tharmanathan, P., Volz, HP., et al.[2022]

A predictive model using machine learning was developed to estimate depression symptom severity in patients with treatment-resistant depression (TRD), based on 116 clinical and demographic variables from a dataset of 5,356 PHQ-9 scores.

The model achieved an accuracy of 62.7%, indicating it can effectively categorize depression severity, which could help healthcare systems tailor treatments for TRD patients, although there is potential for further improvement in its accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How well do clinical and demographic characteristics predict Patient Health Questionnaire-9 scores among patients with treatment-resistant major depressive disorder in a real-world setting? Voelker, J., Joshi, K., Daly, E., et al.[2022]

Achieving remission from depression, rather than just a 50% reduction in symptoms, is crucial for improving patients' quality of life and reducing relapse risk, as supported by clinical experience and research.

Pooled data from over 2000 patients indicate that venlafaxine, which works on multiple neurotransmitter systems, is significantly more effective than selective serotonin reuptake inhibitors in achieving remission and preventing relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinician perspective on achieving and maintaining remission in depression. Kelsey, JE.[2005]

JNJ-7925476 is a potent triple reuptake inhibitor that effectively blocks serotonin, norepinephrine, and dopamine transporters, showing a strong ability to increase levels of these neurotransmitters in the brain, which is crucial for treating depression.

In animal models, JNJ-7925476 demonstrated significant antidepressant-like effects, with an effective dose (ED50) of 0.3 mg/kg, indicating its potential as a new therapeutic option for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro and in-vivo characterization of JNJ-7925476, a novel triple monoamine uptake inhibitor. Aluisio, L., Lord, B., Barbier, AJ., et al.[2008]

The XNJY decoction significantly improved depressive-like behaviors in a rat model of poststroke depression (PSD) after 21 days of treatment, showing its potential as an effective antidepressant.

The antidepressant effects of XNJY are likely linked to its ability to enhance neuronal survival and regulate the BDNF/ERK/CREB signaling pathway, increasing levels of serotonin, norepinephrine, and BDNF in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats. Li, T., Wang, D., Zhao, B., et al.[2020]

In a study involving 40 Wistar rats, the Kaixin Jieyu Decoction (KJD) significantly improved depression-like behaviors and reduced hippocampal damage after 21 days of treatment, indicating its potential as an effective anti-depressant.

The mechanism of KJD's protective effects appears to be linked to the promotion of glial fibrillary acidic protein (GFAP) expression in the hippocampus, which is associated with brain health and recovery from depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of kaixin jieyu decoction on behavior and glial fibrillary acidic protein expression in cerebral hippocampus of a rat vascular depression model. Zhang, XH., Huang, SJ., Wang, YY., et al.[2021]

Two fractions of Gardenia jasminoides, specifically petroleum ether (GJ-PE) and n-butyl alcohol (GJ-BO), demonstrated rapid antidepressant effects in mice, as shown by behavioral tests like the forced swimming test (FST) and tail suspension test (TST).

The antidepressant effects of GJ-PE were linked to increased levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, suggesting a mechanism of action that involves BDNF signaling, while GJ-BO did not show this association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two standardized fractions of Gardenia jasminoides Ellis with rapid antidepressant effects are differentially associated with BDNF up-regulation in the hippocampus. Ren, L., Tao, W., Zhang, H., et al.[2017]

The Chinese herbal formula SYJN, consisting of four herbs, demonstrated an antidepressant-like effect in a rat model of chronic unpredictable stress, suggesting its potential as a treatment for depression.

SYJN appears to work by increasing the expression of neurotrophin-3 (NT-3) and nerve growth factor (NGF) in the brain, which were significantly decreased in stressed rats, indicating a possible mechanism for its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herbal formula SYJN increases neurotrophin-3 and nerve growth factor expression in brain regions of rats exposed to chronic unpredictable stress. Mao, QQ., Zhong, XM., Li, ZY., et al.[2011]

References

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

Venlafaxine for treatment-resistant unipolar depression. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging antidepressants to treat major depressive disorder. [2016]

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

The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. [2022]

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

How well do clinical and demographic characteristics predict Patient Health Questionnaire-9 scores among patients with treatment-resistant major depressive disorder in a real-world setting? [2022]

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

Clinician perspective on achieving and maintaining remission in depression. [2005]

6. Netherlands pubmed.ncbi.nlm.nih.gov

In-vitro and in-vivo characterization of JNJ-7925476, a novel triple monoamine uptake inhibitor. [2008]

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

Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats. [2020]

8. China pubmed.ncbi.nlm.nih.gov

Effects of kaixin jieyu decoction on behavior and glial fibrillary acidic protein expression in cerebral hippocampus of a rat vascular depression model. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Two standardized fractions of Gardenia jasminoides Ellis with rapid antidepressant effects are differentially associated with BDNF up-regulation in the hippocampus. [2017]

10. Ireland pubmed.ncbi.nlm.nih.gov

Herbal formula SYJN increases neurotrophin-3 and nerve growth factor expression in brain regions of rats exposed to chronic unpredictable stress. [2011]