Fosigotifator for Depression

Recruiting at 3 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AbbVie

Must be taking: Antidepressants

Disqualifiers: Other psychiatric illness

Trial Summary

What is the purpose of this trial?

Major depressive disorder (MDD; depression) is a mood disorder that causes a continued feeling of sadness and loss of interest. It is a common and serious illness that can cause both emotional and physical symptoms such as feelings of sadness, irritability, not being able to focus on activities, tiredness, changes in eating habits, and aches and pains. The main goal of the study is to evaluate how safe and effective fosigotifator is in treating MDD. Fosigotifator (ABBV-CLS-7262) is a new treatment being developed for adult patients with depression. This study is double-blinded, which means that neither the patients nor the study doctors know who is given fosigotifator and who is given placebo. Participants will be randomly assigned to one of the two groups to receive fosigatofator or placebo. There is 1 in 2 chance that participants will receive placebo. Approximately 106 adult participants with MDD will be enrolled in approximately 15 sites across the world. Participants will receive oral fosigotifator or matching placebo. Duration of the study is approximately 144 days. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular weekly visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Will I have to stop taking my current medications?

If you are currently taking antidepressant therapy, you must be able to safely stop taking it at least 7 days before starting the study medication.

What makes the drug Fosigotifator unique for treating depression?

Fosigotifator is unique because it is a new type of drug that may work by specifically targeting serotonin (a brain chemical that affects mood) uptake, potentially offering a different mechanism of action compared to traditional antidepressants, which often have broader effects on the nervous system. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with Major Depressive Disorder as defined by the DSM-5, experiencing a depressive episode lasting 6 weeks to less than 2 years. Participants must need antidepressant therapy or be able to stop current medication safely for at least 7 days before starting the study drug.

Inclusion Criteria

Meets the following disease activity criteria mentioned in the protocol

Body mass index of 18 to 33 kg/m2 at the time of consent

Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for MDD based on the Structured Clinical Interview for DSM-5

Exclusion Criteria

Primary psychiatric illness other than MDD

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral fosigotifator or matching placebo for approximately 114 days

16 weeks

Regular weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fosigotifator (ABBV-CLS-7262) (Other)

Trial Overview The trial tests Fosigotifator's safety and effectiveness against depression compared to a placebo. It's double-blinded, meaning neither doctors nor patients know who receives the actual drug or placebo. The treatment involves weekly visits, medical assessments, blood tests, side effect monitoring, and questionnaires.

Participant Groups

Group I: Fosigotifator Experimental Treatment 1 Intervention

Participants will receive fosigotifator.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo for fosigotifator.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

FG4963 is a new phenylpiperidine derivative that effectively blocks the serotonin (5HT) uptake in the brain, showing similar activity to the established antidepressant chlorimipramine.

Unlike traditional tricyclic antidepressants, FG4963 has a weaker effect on norepinephrine (NA) uptake and appears to have less impact on peripheral organ functions, suggesting it may have a safer profile with fewer side effects related to the autonomic nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical and pharmacological studies on a new 5HT-uptake inhibitor, FG4963, with potential antidepressant properties. Lassen, JB., Squires, RF., Christensen, JA., et al.[2020]

The study found that certain 5-HT receptor ligands, particularly RU 24,969 and 5-CT, effectively inhibit cyclic AMP formation and enhance fibroblast growth factor-induced cell growth in CHL fibroblasts, indicating their potential as effective agonists at the 5-HT1B receptor.

Beta adrenergic receptor antagonists, such as propranolol and pindolol, exhibited antagonist activity at the 5-HT1B receptor in CHL fibroblasts, suggesting that these compounds can modulate 5-HT1B receptor functions differently than in other cell types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential functional activity of 5-hydroxytryptamine receptor ligands and beta adrenergic receptor antagonists at 5-hydroxytryptamine1B receptor sites in Chinese hamster lung fibroblasts and opossum renal epithelial cells. Pauwels, PJ., Palmier, C.[2013]

The novel 5-HT1D receptor antagonist GR 127,935 demonstrated potent antagonism at the 5-HT1D beta receptor sites with a very low KB value of 1.3 nM, indicating strong efficacy in blocking this receptor.

While GR 127,935 showed some agonist activity at 5-HT1A and 5-HT1B receptors, its antagonistic effects were weaker at 5-HT1D alpha and 5-HT1B receptors, suggesting a selective action that could be beneficial for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional effects of the 5-HT1D receptor antagonist GR 127,935 at human 5-HT1D alpha, 5-HT1D beta, 5-HT1A and opossum 5-HT1B receptors. Pauwels, PJ., Palmier, C.[2019]

SB-271046, a selective 5-HT6 antagonist, is being developed as a potential cognition enhancer, particularly for cognitive disorders like Alzheimer's disease, with phase I trials starting in December 1999.

Administration of SB-271046 significantly increased levels of glutamate and aspartate in the frontal cortex, suggesting its potential effectiveness in treating cognitive dysfunction without affecting other neurotransmitter levels like noradrenaline, dopamine, or serotonin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SB-271046 (SmithKline Beecham). Miguel-Hidalgo, JJ.[2018]

In a study of 35 normal tension glaucoma patients over 8 to 11 months, those treated with Naftidrofuryl (200 mg twice daily) showed a significant improvement in visual acuity compared to untreated patients (p = 0.001).

The treated group also experienced a significant increase in mean sensitivity (MS) (p = 0.03), suggesting that Naftidrofuryl may have beneficial effects on visual function in glaucoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of normal pressure glaucoma with a serotonin S2 receptor antagonist, naftidrofuryl (praxilen)]. Mermoud, A., Faggioni, R.[2013]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Neurochemical and pharmacological studies on a new 5HT-uptake inhibitor, FG4963, with potential antidepressant properties. [2020]

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

Differential functional activity of 5-hydroxytryptamine receptor ligands and beta adrenergic receptor antagonists at 5-hydroxytryptamine1B receptor sites in Chinese hamster lung fibroblasts and opossum renal epithelial cells. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Functional effects of the 5-HT1D receptor antagonist GR 127,935 at human 5-HT1D alpha, 5-HT1D beta, 5-HT1A and opossum 5-HT1B receptors. [2019]

4. England pubmed.ncbi.nlm.nih.gov

SB-271046 (SmithKline Beecham). [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of normal pressure glaucoma with a serotonin S2 receptor antagonist, naftidrofuryl (praxilen)]. [2013]