A Study to Assess the Efficacy, Safety and Tolerability of VLS-01 Buccal Film, Compared to Placebo in Patients With Treatment Resistant Depression (ELUMINA)

A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Assess the Efficacy, Safety, and Tolerability of Repeated Doses of VLS-01 Buccal Film in Participants With Treatment Resistant Depression

This Phase 2 study (protocol number VLS-01-203) will determine the efficacy, safety, and tolerability of short-term treatment with a VLS-01 transmucosal buccal film (VLS-01-BU) in patients with treatment resistant Major Depressive disorder (TRD) and will characterize the onset and durability of antidepressant effects of VLS-01-BU versus placebo.

Study Overview

• Status: Recruiting
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: VLS-01-203 BU; Drug: VLS-01-BU Placebo

Detailed Description

This Phase 2, multicenter, double-blind, randomized, placebo-controlled trial will enroll approximately 142 participants with TRD, randomized 1:1 to receive a total of 2 double-blind administrations of VLS- 01-BU (buccal film containing VLS-01) or placebo, administered via the buccal transmucosal route, with a 2-week interval between each administration, during the placebo-controlled treatment period. All participants will have their symptoms monitored for 12 weeks in the placebo- controlled follow-up period, following the second administration of VLS-01-BU or placebo. After the placebo-controlled treatment and observation period all participants will be re-randomized 1:1 to receive one double-blinded administration of VLS-01-BU (dose strength 1 or dose strength 2) during a non-placebo-controlled treatment period. Final safety and efficacy assessment will be conducted two weeks after administration of the third dose.

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kevin Craig, MD; Phone Number: +1 332-282-0507; Email: clinicaltrials@atai.life

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, NSW 2050
      • Recruiting
      • Royal Prince Alfred Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Sydney Local Health District (SLHD) Mental Health
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Recruiting
      • NeuroCentrix
    • Carlton, Victoria, Australia, 3053
      • Recruiting
      • The University of Melbourne
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Royal Melbourne Hospital
    • Northcote, Victoria, Australia, 3070
      • Recruiting
      • Paratus Clinical Research Melbourne
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • University of Melbourne
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital Parkville
• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0E8
      • Recruiting
      • Centre for Neurology Studies
  • Ontario
    • Kingston, Ontario, Canada, K7L 4X3
      • Recruiting
      • Providence Care Hospital
• United Kingdom
  • London, United Kingdom, W1G 8DR
    • Recruiting
    • Clerkenwell Health
  • England
    • Doncaster, England, United Kingdom, DN 4 8QN
      • Recruiting
      • Clerkenwell Health
    • London, England, United Kingdom, W1U 6RP
      • Recruiting
      • Clerkenwell Health
    • Motherwell, England, United Kingdom, ML1 4UF
      • Recruiting
      • NeuroClin
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Recruiting
      • Noble Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Preferred Research Partners, Inc.
    • Little Rock, Arkansas, United States, 72204
      • Recruiting
      • Pillar Clinical Research, LLC
    • Rogers, Arkansas, United States, 72758
      • Recruiting
      • Woodland Research Northwest
  • California
    • Garden Grove, California, United States, 92845
      • Recruiting
      • CenExel
    • Glendale, California, United States, 91206
      • Recruiting
      • Behavioral Research Specialists, LLC
    • La Jolla, California, United States, 92037
      • Recruiting
      • Kadima Neuropsychiatry Institute
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Collaborative Neuroscience Research, LLC
    • Santa Monica, California, United States, 90404
      • Recruiting
      • TRIP Clinical at Psychedelic Science Institute
  • Colorado
    • Denver, Colorado, United States, 80209
      • Recruiting
      • Mountain View Clinical Research Inc.
      • Contact: David Weiss, MD; Phone Number: 720-941-9363
  • Florida
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • CenExel
    • Miami, Florida, United States, 33155
      • Recruiting
      • BioResearch Partner
    • Tampa, Florida, United States, 33613
      • Recruiting
      • University of South Florida, Psychiatry and Behavioral Neurosciences
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Recruiting
      • CenExcel
    • Savannah, Georgia, United States, 31405
      • Recruiting
      • CenExel
  • Illinois
    • Chicago, Illinois, United States, 60641
      • Recruiting
      • Pillar Clinical Research LLC
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Recruiting
      • Sheppard Pratt
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Sunstone Medical, PC
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • Recruiting
      • Elixia MA
    • Watertown, Massachusetts, United States, 02472
      • Recruiting
      • Adams Clinical
  • Minnesota
    • Eden Prairie, Minnesota, United States, 55347
      • Recruiting
      • Institute for Integrative Therapies
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Recruiting
      • Midwest Research GRoup
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Recruiting
      • Clinilabs, LLC
    • Toms River, New Jersey, United States, 08755
      • Recruiting
      • Bio Behavioral Health
  • New York
    • New York, New York, United States, 10128
      • Recruiting
      • The Medical Research Network, LLC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
    • North Canton, Ohio, United States, 44720
      • Recruiting
      • Neuro Behavioral Clinical Research, Inc.
  • Pennsylvania
    • Moosic, Pennsylvania, United States, 18507
      • Recruiting
      • Scranton Medical Institute, LLC
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
  • Texas
    • Austin, Texas, United States, 78759
      • Recruiting
      • BioBehavioral Research of Austin
    • DeSoto, Texas, United States, 75115
      • Recruiting
      • InSite Clinical Research
    • Plano, Texas, United States, 75093
      • Recruiting
      • AIM Trials, LLC
  • Utah
    • Draper, Utah, United States, 84020
      • Recruiting
      • Cedar Clinical Research Inc
  • Washington
    • Bellevue, Washington, United States, 98004
      • Recruiting
      • Seattle Neuropsychiatric Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 to 65 years of age inclusive at the time of signing the Informed Consent.
• Has a diagnosis of recurrent moderate or severe MDD without psychotic features or single- episode MDD with duration greater than or equal to 3 months without psychotic features and is currently experiencing a major depressive episode.
• Onset of first episode of MDD occurred before age 55.
• Has not responded to an adequate dose and duration of at least two and no more than five antidepressant medications for the current depressive episode, as determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH- ATRQ).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion Criteria:

• Has a current or prior DSM-5-TR diagnosis of a schizophrenia spectrum and other psychotic disorder, substance/medication-induced psychotic disorder, bipolar and related disorder, or any disorder with psychotic features.
• Has a moderate or severe substance use disorder (drug, alcohol, or tobacco) within the 6 months before Screening and/or history of moderate or severe substance use disorder (drug alcohol) within the previous 1 year before Screening
• Has a history of, or current signs and symptoms of, diseases or conditions that would make participation not be in the best interest (e.g., compromise the wellbeing) of the participant or that could prevent, limit, or confound the protocol-specified assessments.
• Has suicidal ideation with some intent to act within 6 months before Screening or a history of suicidal behavior within the past 1 year before Screening.
• Has a history of clinically significant cardiovascular, cerebrovascular, or peripheral vascular disease or condition, including but not limited to unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, valvular heart disease, obstructive coronary artery disease, hypertension, hypotension, bradycardia, tachycardia, or risk factors for long QT Syndrome.
• Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before Screening.
• Has any known allergy or hypersensitivity to VLS-01 or to any of the excipients in the formulation.
• Has recently initiated and is currently undergoing directive psychotherapy (e.g., cognitive behavioral therapy, interpersonal psychotherapy, psychodynamic psychotherapy) within the past 30 days before Screening. Participants planning to initiate individual or group therapy during the study are also not eligible.
• Has received any prohibited therapies.
• Has clinically significant laboratory abnormalities at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLS-01-BU	Drug: VLS-01-203 BU; VLS-01 buccal transmucosal administration
Placebo Comparator: VLS-01-BU Placebo	Drug: VLS-01-BU Placebo; Placebo buccal transmucosal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score	Baseline to Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in MADRS total score	Baseline to Day 43

Other Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events, adverse events of special interest and serious adverse events	Baseline to Day 113
Incidence of clinically significant abnormalities in physical examinations, vital signs, electrocardiogram parameters, and safety laboratory results	Baseline to Day 113
Columbia-Suicide Severity Rating Scale (C- SSRS) scores	Baseline to Day 113

Collaborators and Investigators

• Sponsor: atai Therapeutics, Inc.
• Investigators: Principal Investigator: Kimball A Johnson, MD, CenExel iResearch, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: July 24, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Mood Disorders; Depressive Disorder; Treatment Resistant Depression; Mental Disorders; Major Depression; Depressive Disorder, Major; Antidepressive Agents; Psychotropic Drugs; Behavioral Symptoms; Depressive Disorder, Treatment-Resistant
• Additional Relevant MeSH Terms: Behavior; Depression; Depressive Disorder; Mood Disorders; Mental Disorders; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms
• Other Study ID Numbers: VLS-01-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No