A Biomarker-Guided, Randomized, Placebo-Controlled Efficacy and Safety Study of Liafensine in Patients With TRD

NCT05113771 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DB104-01
• Study Type: interventional
• Target: 197
• Locations: 2 countries
• Sites: 45

Brief Summary

This study was conducted as a randomized, double-blind, placebo-controlled, multi-center Phase 2b study. Approximately 180 subjects with treatment resistant depression who meet all eligibility criteria will be enrolled. The primary endpoint is to demonstrate liafensine is superior to placebo in DGM4 positive patients with TRD.

Conditions

Treatment Resistant Depression

Keywords

TRD, Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score From Baseline to Day 42, in DGM4-positive Patients

  The primary objective of this study was change of Montgomery Åsberg Depression Rating Scale (MADRS) total score (range = 0 60, with higher scores indicating more severe depression) in DGM4 positive patients who were treated with liafensine versus placebo.

  Baseline to Day 42

Secondary Outcomes (2)

• Change From Baseline to Day 42 in Clinical Global Impression-Severity Scale (CGI-S) Score in DGM4 Positive Patients

  Baseline to Day 42

• The Clinical Global Impression-Improvement Scale (CGI-I) (Range = 1-7, With Higher Score Indicating Worsening) Was Assessed in DGM4 Positive Patients

  42 days

Study Arms (3)

Liafensine 1mg

EXPERIMENTAL

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

Drug: Liafensine

Liafensine 2mg

EXPERIMENTAL

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

Drug: Liafensine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Liafensine DRUG

Liafensine

Also known as: DB104

Liafensine 1mg; Liafensine 2mg

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed informed consent which includes pharmacogenomic (PGx) testing.
• Have a diagnosis of MDD without psychotic features, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, based on clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Have a history of TRD within the past 5 years as documented by the Massachusetts General Hospital (MGH) Antidepressant Treatment Response Questionnaire (ATRQ) (5-year version). That is, within the past 5 years study participants must have had a clinically meaningful inadequate response (estimated \< 50% improvement per Investigator/patient consensus and documented by the Investigator) to at least two treatment courses with antidepressant regimens. These must involve at least two different pharmacologic treatment classes\* and have been given at accepted therapeutic doses for an adequate duration (at least 6 weeks). One of these treatment failures must have occurred within the current episode.
• \*Note: Non-pharmacological treatment (eg, cognitive behavioral therapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation, vagus nerve stimulation, acupuncture) are not counted as treatment regimen.
• To be eligible, patients must have DGM4 genotype results obtained from the designated Clinical Laboratory Improvement Amendments (CLIA) lab, and all eligible DGM4-positive patients and about 20% DGM4-negative patients will be randomly included by an IRT system in order to achieve the appropriate randomization ratio of DGM4-positive vs negative patients.
• Pregnancy conception limitations
• Female patients must be postmenopausal or surgically sterile or, if of childbearing potential and the partner is not vasectomized (6 months minimum), must agree to use a medically acceptable form of contraception from the time of signing the informed consent form (ICF) through at least 60 days following the last administration of study drug. If only the barrier method is used, a double barrier must be employed. Postmenopausal women must have had ≥ 24 months of spontaneous amenorrhea. Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy, or bilateral tubal ligation. All women of childbearing potential must have a negative pregnancy test result before administration of study drug.
• Male patients must be biologically incapable of having children (eg, vasectomized) or must agree to use the above forms of birth control for themselves and their partner from the time of signing the informed consent form through at least 120 days following the last administration of study drug.
• Be fluent in the local language.
• Male or female aged 18 to 70, inclusive, at time of enrollment.
• Have a HAMD-17 total score ≥ 21 at screening.
• Be willing to discontinue the use of antidepressant drugs (including over-the-counter medications to treat depression \[eg, St John's Wort\]) at least 5 half-lives (or at least 1 week for herbal or other over-the-counter medications for depression) prior to baseline (Day -1). For fluoxetine, a washout period of at least 3 weeks for ≤ 20 mg/day and at least 4 weeks for \> 20 mg/day is required.

You may not qualify if:

• Prior participation in a study with liafensine
• Used any investigational drug product, device, or biologic within 6 months or five half-lives (whichever is longer) prior to baseline (Day -1).
• A positive pregnancy test result or currently breastfeeding.
• Clinically significant illness (including chronic, persistent, or acute infection), medical/surgical procedure, or trauma within 30 days prior to screening or between screening and baseline (Day 1) as determined by the investigator.
• A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, respiratory, immunologic, hematologic, dermatologic, or neurologic abnormality, or any other condition, that in the investigator's opinion, represent potential risk to the patient's safety, full participation in the study, or affect the absorption, distribution, metabolism, or excretion of liafensine.
• Presence of autoimmune hepatitis, primary sclerosing cholangitis, untreated hepatitis C, active hepatitis B, or any other uncontrolled or unstable liver disease according to local guidance.
• Uncontrolled human immunodeficiency virus (HIV) infection according to local guidance.
• Uncontrolled abnormal thyroid function according to local guidance.
• One or more clinical laboratory evaluations are outside the reference range, at screening, that are in the investigator's opinion, of potential risk to the patient's safety.
• Has at the Screening Visit:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 1.5x the upper limit of normal (ULN) at screening.
• Total bilirubin (TBL) \> 2 mg/dL (34.2 μmol/L) at screening, unless there is an explained indirect hyperbilirubinemia, eg, Gilbert's syndrome.
• Alkaline phosphatase (ALP) \> 1.5x the ULN at screening. Note: Laboratory tests can be repeated to see if values return to normal range, but any such laboratory abnormality must be resolved by the Baseline Visit (Day -1).
• Clinically significant vital sign abnormality at screening. This includes, but is not limited to, the following, in the supine (after at least 5 min rest) and standing (after 1 min and 3 min standing): systolic blood pressure ≥ 140 mmHg; diastolic blood pressure ≥ 90 mmHg; or heart rate \< 50 or \> 90 beats per minute. If the initial blood pressure is ≥ 140/90 mmHg, the lowest value from up to 3 additional attempts, which also must not be ≥ 140/90 mmHg, should be used. Patients with symptomatic orthostatic hypotension, at the discretion of investigator, will be excluded.
• Corrected QT interval measurement according to the Fridericia rule (QTcF) \> 450 msec for men and \> 470 msec for women during controlled rest at screening, or history of long-QT syndrome.

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (45)

University of Alabama at Birmingham

Huntsville, Alabama, 35801, United States

Location

Alea Research

Phoenix, Arizona, 85012, United States

Location

Collaborative Neuroschience Research, LLC

Garden Grove, California, 92845, United States

Location

Behavioral Research Specialists, LLC

Glendale, California, 91206, United States

Location

Sunwise Clinical Research, LLC.

Lafayette, California, 94549, United States

Location

Excell Research

Oceanside, California, 92056, United States

Location

Anderson Clinical Reseach

Redlands, California, 92374, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Collaborative Neuroscience Research, LLC

Torrance, California, 90502, United States

Location

Pacific Clinical Research Management Group

Upland, California, 91786, United States

Location

Clinical Research of Brandon, LLC

Brandon, Florida, 33511, United States

Location

Access Research Institute

Brooksville, Florida, 34613, United States

Location

The Medicine Medical Research

Hollywood, Florida, 33121, United States

Location

Nuovida Research Center

Miami, Florida, 33145, United States

Location

SG Research, LLC

Miami, Florida, 33145, United States

Location

Aqualane Clinical Research

Naples, Florida, 34105, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

Location

CenExel Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Psych Atlanta, PC

Marietta, Georgia, 30060, United States

Location

Revive Research Institute, Inc

Elgin, Illinois, 60123, United States

Location

Ascension Via Christi Research, a division of Ascension Via Christi Hospitals Wichita, Inc.

Wichita, Kansas, 67214, United States

Location

Pharmasite Research, Inc.

Baltimore, Maryland, 21208, United States

Location

CBH Health LLC

Gaithersburg, Maryland, 20877, United States

Location

Boston Clinical Trials & Medical Research

Boston, Massachusetts, 02131, United States

Location

Neurobehavioral Medicine Group

Bloomfield, Michigan, 48302, United States

Location

Alivation Research, LLC

Lincoln, Nebraska, 68526, United States

Location

Altea Research Institute, Las Vegas

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

Global Medical Institutes, LLC

Princeton, New Jersey, 08510, United States

Location

Global Medical Institutes, LLC

Princeton, New Jersey, 08540, United States

Location

Bio Behavior Health

Toms River, New Jersey, 08755, United States

Location

IMA Clinical Research

Albuquerque, New Mexico, 87109, United States

Location

Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

The Ohio State University Department of Psychiatry

Columbus, Ohio, 43210, United States

Location

Lehigh Center for Clinical Research, LLC

Allentown, Pennsylvania, 18104, United States

Location

Global Medical Institutes, LLC

Moosic, Pennsylvania, 18507, United States

Location

FutureSearch Trials of Dallas

Dallas, Texas, 75231, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

North Texas Clinical Trials

Fort Worth, Texas, 76014, United States

Location

University of Texas Medical School at Houston

Houston, Texas, 77054, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

OCT Research ULC

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

AMNDX Inc.

Markham, Ontario, L3R 1A3, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B1M4, Canada

Location

CAMH-Russell Street Site 250 College Street

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (1)

• Wang G, Aguado M, Spear MA, Alphs L, Chen C, Huang H, Lu XX, Doostzadeh J, Wu S, Wang S, Patel A, Nemeroff CB, Wang Z, Li A, Luo W. ANK3 as a Novel Genetic Biomarker for Liafensine in Treatment-Resistant Depression: The ENLIGHTEN Randomized Clinical Trial. JAMA Psychiatry. 2025 Dec 1;82(12):1186-1194. doi: 10.1001/jamapsychiatry.2025.2416.

  PMID: 40928787 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Julie Doostzadeh, Executive Director
• Organization: Denovo Biopharma

jdoostzadeh@denovobiopharma.com

858-799-1021

Study Officials

• Matthew A Spear, M.D.

  Denovo Biopharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2021
• First Posted: November 9, 2021
• Study Start: June 29, 2022
• Primary Completion: February 6, 2024
• Study Completion: March 5, 2024
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (41); CA (4)