Fosigotifator for Depression

No longer recruiting at 3 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must be taking: Antidepressants

Disqualifiers: Other psychiatric illness

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called fosigotifator for adults with major depressive disorder (MDD), a mood disorder causing persistent sadness and loss of interest in daily activities. The study aims to determine the safety and effectiveness of fosigotifator in treating these symptoms. Participants will be randomly assigned to receive either the drug or a placebo, with neither the participants nor the doctors knowing which is administered. Those who have experienced a major depressive episode lasting between six weeks and two years and require antidepressant therapy might be suitable candidates. Participants must attend weekly check-ups and complete various assessments over approximately 144 days. As a Phase 1 trial, this research focuses on understanding how fosigotifator works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that fosigotifator is likely to be safe for humans?

Research has shown that fosigotifator has been tested for safety in humans. In earlier studies with patients who have conditions like amyotrophic lateral sclerosis (ALS), fosigotifator proved to be safe and generally well-tolerated. The side effects resembled those seen with other treatments, indicating it did not cause more problems than expected.

Although this trial focuses on major depressive disorder (MDD), the safety data from past studies in other conditions offers some reassurance. However, since this is an early-phase study for MDD, researchers are still collecting detailed safety information specific to this condition. Participants in this trial will help further understand how people with depression respond to fosigotifator in terms of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fosigotifator is unique because it represents a new approach for treating depression by targeting specific pathways in the brain that aren't addressed by traditional antidepressants like SSRIs or SNRIs. Most current treatments for depression work by increasing levels of neurotransmitters like serotonin and norepinephrine, but fosigotifator works differently, potentially offering benefits for patients who haven't responded to standard therapies. Researchers are excited about fosigotifator because it could provide a faster onset of relief and potentially fewer side effects compared to existing medications.

What evidence suggests that fosigotifator might be an effective treatment for depression?

Research has shown that fosigotifator, which participants in this trial may receive, activates a specific protein pathway called eIF2B. This activation helps nerve cells continue normal protein production, even under stress. This process is important because it might alleviate stress-related issues common in major depressive disorder (MDD). Early studies suggest that targeting this pathway could improve depression symptoms. However, as this is a new treatment, more information is needed to fully understand its effectiveness for MDD. Initial data from related conditions, such as ALS, are promising, but the evidence is still developing. ^{1 2 3 4 5}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fosigotifator (ABBV-CLS-7262)

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M24-840

A Study to Assess Adverse Events of Fosigotifator (ABBV- ... A Study to Assess Adverse Events of Fosigotifator (ABBV-CLS-7262) in Adults With Major Depressive Disorder. Study ID: M24-840. ClinicalTrials.gov ID:.

2. trial.medpath.com trial.medpath.com/drug/report/86892eab963fd37d

ABBV-CLS-7262 | Advanced Drug Monograph - MedPath Comprehensive analysis about ABBV-CLS-7262, including its mechanisms, clinical uses, and therapeutic considerations.

3. calicolabs.com calicolabs.com/press/calico-statement-on-fosigotifator-in-healey-als-platform-trial/

Calico Provides Update on Fosigotifator in HEALEY ALS ... By activating eIF2B, fosigotifator could attenuate the ISR pathway and restore normal protein production in stressed nerve cells, potentially ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04948645

NCT04948645 | A Phase 1 Study to Investigate the Safety ... Fosigotifator is an investigational drug being researched for the treatment of Amyotrophic Lateral Sclerosis. This is an up to 156-week, 2-part study. Part 1 ...

5. massgeneral.org massgeneral.org/neurology/als/news/healeyamg-announces-platform-trial-update-fosigotifator

Sean M. Healey & AMG Center Announces Update in ALS ... We remain deeply committed to fully understanding the effects of fosigotifator in ALS, and will further evaluate the data before determining ...