ARD-101 for Treatment of PWS: The Hunger Elimination or Reduction Objective Trial (HERO)

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of ARD-101 for the Treatment of Hyperphagia in Patients With Prader-Willi Syndrome

The goal of this clinical trial is to learn if ARD-101 works to treat hyperphagia-related behavior in patients with Prader-Willi syndrome (PWS). It will also teach us about the safety of ARD-101.

The main questions it aims to answer are:

• Does ARD-101 improve the total score of the HQCT-9 (hyperphagia questionnaire for clinical trials, 9 questions)?
• What medical problems do participants have when taking ARD-101?

Researchers will compare ARD-101 to a placebo (a look-alike substance that contains no drug) to see if ARD-101 works to treat hyperphagia in PWS subjects.

Eligible participants will:

• Take ARD-101 or a placebo every day for 12 weeks.
• Visit the clinic or have a tele-visit once every 2 to 4 weeks during dosing and then have a tele-visit 4 weeks after stopping the ARD-101 or placebo.
• Patients/Caregivers will keep a daily diary.

Participants who complete the study may be eligible to enter an open-label extension study where everyone will receive ARD-101.

Study Overview

• Status: Suspended
• Conditions: Hyperphagia; Prader-Willi Syndrome
• Intervention / Treatment: Drug: ARD-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital Research Institute
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital at London Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
• South Korea
  • Incheon, South Korea, 22332
    • Inha University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Suwon, South Korea, 16499
    • Ajou University Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB21 5EF
    • Fulborn Hospital
  • Glasgow, United Kingdom, G51 4TF
    • Royal Hospital for Children (Glasgow) - PPDS - PIN
  • London, United Kingdom, E1 4NS
    • The Royal London Hospital
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1711
      • Children's of Alabama
  • California
    • Encinitas, California, United States, 92123
      • Rady Children's Hospital
    • Orange, California, United States, 92868
      • Children's Hospital of Orange Country
    • Palo Alto, California, United States, 94304
      • Stanford Children's Health Specialty Services
  • Colorado
    • Denver, Colorado, United States, 80045-7106
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803-3607
      • Nemours Children Clinic Wilmington
  • Florida
    • Gainesville, Florida, United States, 32610-3008
      • UF Shands Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322-1047
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611-2991
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287-0005
      • The Johns Hopkins Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55102
      • University of Minnesota Masonic Children's Hospital
  • New York
    • Brooklyn, New York, United States, 11219-2918
      • Maimonides Medical Center
    • Mineola, New York, United States, 11501-4077
      • NYU Langone Children's Ambulatory Care Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0005
      • Vanderbilt University Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documented confirmation of Prader-Willi Syndrome (PWS)
• Stable care setting with same, single designated caregiver for at least 6 months prior to Visit 1
• At least 7 years of age or older in the US at the time of consent
• At least 10 years of age or older in Australia
• At least 13 years of age or older in countries outside of the US and Australia

Exclusion Criteria:

• Diagnosis of schizophrenia, bipolar disorder, personality disorder or other severe mood, anxiety or eating disorder (other than hyperphagia).
• Presence of any malignancy within 5 years with the exception of basal or squamous cell carcinoma of the skin, in situ carcinoma of the service, or in situations prostate cancer.
• Presence of clinically relevant renal, hepatic, pancreatic, cardiovascular, neurological, psychiatric, hematological, pulmonary, or GI abnormality that, in the opinion of the investigator, may preclude the patient from safe completion of the study
• Adults: systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg
• Children and Adolescents: systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg.
• Type 1 diabetes mellitus; HbA1c >8.5%
• Use of agents to promote weight gain or loss, alter hunger or appetite within 30 days of Visit 1 and throughout the study.
• Use of any commercially available medication for the treatment of hyperphagia (i.e., Vykat) within 60 days of randomization and throughout the study.
• Very high doses of glucocorticoids in the previous 3 months of Visit 1 and throughout the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A; ARD-101	Drug: ARD-101; 200 mg BID (twice per day) for 1 week, 400 mg BID for 1 week, 800 mg BID for 10 weeks
Placebo Comparator: Treatment Arm B; Placebo for ARD-101	Drug: Placebo; 200 mg BID (twice per day) for 1 week, 400 mg BID for 1 week, 800 mg BID for 10 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Score	The HQ-CT score is a 9 question, 5-point scale to describe the PWS patient's hyperphagia food-related problem behaviors. It is completed by the patient's caregiver. Each question is scored from 0 to 4. The minimum total score is 0 (hyperphagia related behavior symptoms not exhibited) and the maximum total score is 36 (hyperphagia related behavior symptoms are observed).	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Caregiver Global Impression of Severity (CaGI-S) for Hyperphagia in Prader-Willi patients	The CaGI-S is a single-item, 7-point scale to describe the severity of the PWS patient's hyperphagia (excessive hunger). It is completed by the patient's caregiver. The minimum score is 1 (not present) and the maximum score is 7 (extremely severe). A higher score indicates a worse severity of hyperphagia.	Baseline to Week 12
Change in Clinical Global Impression of Severity (CGI-S) Score for Hyperphagia in Prader-Willi patients	The CGI-S is a single-item, 7-point scale designed to assess the severity of the PWS patient's hyperphagia (excessive hunger). It is assessed by the clinician and considers the clinician's experience with the PWS population. The minimum score is 1 (normal, not at all ill) and the maximum score is 7 (among the most extremely ill patients). A higher score indicates a worse severity of hyperphagia.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Aardvark Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Prader-Willi Syndrome; PWS; Prader-Willi; Prader Willi Syndrome; Prader Willi; ARD-101
• Additional Relevant MeSH Terms: Imprinting Disorders; Neurologic Manifestations; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Overnutrition; Signs and Symptoms, Digestive; Neurobehavioral Manifestations; Congenital Abnormalities; Abnormalities, Multiple; Overweight; Intellectual Disability; Obesity; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Prader-Willi Syndrome; Hyperphagia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: AVK-101-301

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