Liafensine for Treatment Resistant Depression

(ENLIGHTEN Trial)

No longer recruiting at 41 trial locations

Overseen By Vineela Mallireddy

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Denovo Biopharma LLC

Must not be taking: Antidepressants, ADHD medications

Disqualifiers: Psychotic disorders, Bipolar, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Liafensine, to determine its effectiveness for individuals with depression unresponsive to other treatments. Participants will receive either 1 mg or 2 mg of Liafensine or a placebo (a pill with no active drug) for six weeks. The trial aims to assess whether Liafensine can reduce depression symptoms. Individuals who have experienced depression for the past five years and have tried at least two different antidepressant treatments without success may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking your current antidepressant medications at least 5 half-lives before the trial starts. For fluoxetine, a longer washout period (time without taking the medication) of 3 to 4 weeks is required, depending on the dose.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that liafensine is generally safe and well-tolerated in people with treatment-resistant depression. Previous research reported side effects similar to those in other studies, indicating that most people did not experience unexpected or severe side effects while taking the medication.

In the ENLIGHTEN trial, liafensine was found to be safe for patients. The trial showed no major safety concerns, making liafensine a potential option for those considering joining a trial.

Overall, while some mild side effects might occur, as with any medication, liafensine has demonstrated a good safety record in studies so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Liafensine is unique because it potentially offers a new approach for treating depression, particularly for those with treatment-resistant depression (TRD). Most current antidepressants target neurotransmitters like serotonin, norepinephrine, and dopamine. Liafensine might work differently by targeting specific pathways or receptors that aren't fully addressed by existing medications, potentially leading to improved outcomes for patients who haven't responded well to standard treatments. Researchers are excited because this could mean faster relief and better efficacy for individuals struggling with TRD.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that liafensine may help people with treatment-resistant depression (TRD). In this trial, participants will receive either liafensine at different dosages or a placebo. Earlier studies demonstrated that liafensine worked well for patients with a specific genetic marker called ANK3. These patients experienced significant improvements in their depression symptoms compared to those who took a placebo. Another study found that liafensine greatly reduced depressive symptoms over six weeks. This evidence suggests that liafensine could be a helpful treatment for those with TRD, especially if they have certain genetic markers. ^{4 5 6 7 8}

Who Is on the Research Team?

Matthew A Spear, M.D.

Principal Investigator

Denovo Biopharma

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-resistant Major Depressive Disorder, specifically those with the DGM4 genotype who have tried at least two antidepressants without success in the past 5 years. Men must comply with pregnancy prevention measures. People currently responding well to treatments, with substance abuse issues, significant health abnormalities, or recent cancer history (except certain skin cancers) cannot participate.

Inclusion Criteria

Have you been diagnosed with Major Depressive Disorder?

You have taken two or more different antidepressants within the past 5 years that felt ineffective.

You are currently experiencing depression.

Exclusion Criteria

You have previously taken part in a study involving the drug liafensine.

You have a medical condition that could interfere with how your body processes liafensine.

You have had cancer within the past two years, except for non-spreading skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Liafensine 1mg, Liafensine 2mg, or placebo in a randomized, double-blind manner

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Liafensine
• Placebo

Trial Overview The study tests Liafensine's effectiveness and safety against a placebo in patients with treatment-resistant depression. It's a Phase 2b trial involving about 180 participants who are randomly assigned to receive either Liafensine or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Liafensine 2mg Experimental Treatment 1 Intervention

Patients with TRD were treated with liafensine 2 mg QD for 6 weeks.

Group II: Liafensine 1mg Experimental Treatment 1 Intervention

Patients with TRD were treated with liafensine 1 mg QD for 6 weeks.

Group III: Placebo Placebo Group 1 Intervention

Patients with TRD were treated with placebo 1 mg QD for 6 weeks.

Who Is Running the Clinical Trial?

Denovo Biopharma LLC

Lead Sponsor

Trials

19

Recruited

3,200+

Published Research Related to This Trial

A prediction model was developed using individual patient data from 1493 participants in four clinical trials to estimate the likelihood of responding to placebo in antidepressant trials, with a focus on variables like age and bodily symptoms.

The model showed good calibration and discrimination, indicating it can help identify individuals more likely to respond to placebo, which is crucial for understanding the effects of antidepressants in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data. Shinohara, K., Tanaka, S., Imai, H., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40928787/

ANK3 as a Novel Genetic Biomarker for Liafensine in ... Conclusions and relevance: Liafensine was efficacious and well tolerated in ANK3-positive patients with TRD, with clinically meaningful and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05113771

Study Details | NCT05113771 | A Biomarker-Guided, ... The primary endpoint is to demonstrate liafensine is superior to placebo in DGM4 positive patients with TRD.

3. psychiatrictimes.com psychiatrictimes.com/view/new-biomarker-guided-clinical-trial-of-liafensine-for-treatment-resistant-depression

New Biomarker-Guided Clinical Trial of Liafensine for ... The ENLIGHTEN trial showed liafensine's efficacy in ANK3-positive TRD patients, with significant MADRS score improvements compared to placebo.

4. denovobiopharma.com denovobiopharma.com/en/news_info.html?id=167

News The study demonstrated robust efficacy of DB104 (liafensine) in treatment-resistant depression (TRD) patients carrying a novel pharmacogenomic ...

5. empr.com empr.com/news/liafensine-fast-tracked-for-treatment-resistant-depression/

Liafensine Fast Tracked for Treatment-Resistant Depression Findings showed DGM4-positive patients treated with liafensine experienced highly significant improvement in depressive symptoms over the 6-week ...

6. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2838697

ANK3 as a Novel Genetic Biomarker for Liafensine in ... This randomized clinical trial assesses whether liafensine is efficacious in ANK3-positive patients with treatment-resistant depression.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12423948/

ANK3 as a Novel Genetic Biomarker for Liafensine in ... This randomized clinical trial assesses whether liafensine is efficacious in ANK3-positive patients with treatment-resistant depression.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05113771

Study Details | NCT05113771 | A Biomarker-Guided, ... The primary endpoint is to demonstrate liafensine is superior to placebo in DGM4 positive patients with TRD.