ENCALM: A Study of ENX-102 as a Monotherapy Treatment in Patients With Generalized Anxiety Disorder (ENCALM)

The ENCALM Trial: A Randomized, Double-blind, Placebo-controlled Monotherapy Trial to Evaluate the Efficacy and Safety of ENX-102 in Patients With Generalized Anxiety Disorder

The ENCALM trial is designed to evaluate the efficacy and safety of ENX-102 in patients diagnosed with generalized anxiety disorder (GAD)

Study Overview

• Status: Completed
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: Placebo; Drug: ENX-102

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • IMA Clinical Research Phoenix
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research, LLC (CNS)
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Long Beach, California, United States, 90712
      • Alliance Research
    • Los Angeles, California, United States, 90015
      • NRC Research Institute
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research, LLC
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management Group
    • Walnut Creek, California, United States, 94596
      • Sunwise Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research
  • Florida
    • Clermont, Florida, United States, 34711
      • Vertex Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Lakeland, Florida, United States, 33803
      • Accel Research Sites Network - Lakeland CRU
    • Maitland, Florida, United States, 32751
      • Accel Research Sites Network - Maitland CRU
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
  • Georgia
    • Savannah, Georgia, United States, 31405
      • CenExel iResearch, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Collective Medical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centres
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Ima Clinical Research
  • New York
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78737
      • Austin Clinical Trials Partners
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • AIM Trials
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research Organization
  • Washington
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female at birth, inclusive of any gender identity, aged 18 to 65 years, inclusive, at Screening
• Diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by a Mini-International Neuropsychiatric Interview (MINI) version 7.0.2
• Experiencing clinically significant generalized anxiety in need of treatment as measured by Hamilton Anxiety Rating Scale (HAM-A) Screening and Day 1 scores ≥22 and at least moderately severe score symptoms of anxious mood and tension as measured by HAM-A items 1 and 2, respectively, with score each ≥2 at Screening and Day 1

Key Exclusion Criteria:

• Clinically predominant psychiatric diagnosis other than GAD as confirmed by the MINI
• Any past/lifetime/current diagnosis of a neurocognitive disorder, or psychotic disorder, or any current diagnosis of posttraumatic stress disorder, obsessive compulsive disorder or bipolar disorder confirmed by independent adjudication
• Reports moderately severe to severe symptoms of depression
• Ingested psychotropic medication within 5 half-lives or 21 days (whichever is longer) prior to Day 1, including THC and CBD, and unwillingness to refrain from their use for the entire duration of the trial
• Recent suicidal ideation or behavior
• Current or recent moderate to severe substance use disorder as assessed by the MINI
• Clinically significant abnormal findings in safety assessments
• Has significant progressive disorders or unstable medical conditions
• Unable to comply with the requirements of the study or, in the opinion of the Investigator or Sponsor, is unsuitable for the study

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: ENX-102; Four weeks of 2 mg of ENX-102 in capsule form followed by 3 weeks of tapered dose plus 2 weeks of placebo in capsule form (before and/or after the ENX-102 treatment period), taken orally once daily in the evening for a 9-week total treatment period.	Drug: ENX-102; Selective GABA-A alpha2,3,5 positive allosteric modulator
Placebo Comparator: Placebo; Nine weeks of placebo in capsule form taken orally once daily in the evening for a 9-week total treatment period.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of ENX-102 versus placebo in patients with generalized anxiety disorder (GAD)	Mean change from baseline on the Hamilton Anxiety Rating Scale (HAM-A) total score [14 symptoms with each symptom scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56 and higher scores representing worse outcomes]	4 weeks

Collaborators and Investigators

• Sponsor: Engrail Therapeutics INC
• Investigators: Study Director: Estibaliz Arce, PhD, Engrail Therapeutics INC

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Actual): September 18, 2025
• Study Completion (Actual): September 18, 2025

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Generalized Anxiety Disorder
• Other Study ID Numbers: ENX-102-003

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