Investigation of Sulindac (HLX-0201) and Gaboxadol (HLX-0206) in Male Fragile X Syndrome Patients Aged 13-40 (IMPACT-FXS)

A Phase 2, Placebo-controlled, Adaptive Design Study to Explore the Safety and Efficacy of Sulindac (HLX-0201) and Gaboxadol (HLX-0206) and Possible Other Treatments in Adolescent and Adult Males With Fragile X Syndrome (FXS)

This study is to investigate the safety, tolerability and efficacy of Sulindac (HLX-0201) and Gaboxadol (HLX-0206) in males with Fragile X Syndrome (FXS) with confirmed full FMR1 mutation treated over a 10 week period in an outpatient setting.

Study Overview

• Status: Withdrawn
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Sulindac (HLX-0201), dose strength 1; Drug: Sulindac (HLX-0201), dose strength 2; Drug: Gaboxadol (HLX-0206)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Children's Health Queensland Hospital and Health Service
  • Victoria
    • Caulfield, Victoria, Australia, 3161
      • Fragile X Alliance Clinic
    • Melbourne, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center & Children's Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Insitute
  • Massachusetts
    • Worcester, Massachusetts, United States, 10655
      • University of Massachusetts Chan Medical School
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine (Mount Sinai)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject consents to participate, or if the subject are not the subjects own legal guardian, offers assent supported by legally authorized representative consent. Caregiver also commits to the study requirements prior to any study-related procedures
• Willing and able to comply with the study procedures as specified in the protocol and to comply with the study drug administration
• Subject and caregiver are both able to understand the spoken national language clearly and caregiver can read and write to complete study assessments
• Males aged 13 to 40 years (inclusive)
• Has FXS with molecular genetic confirmation of the full FMR1 mutation (>200 CGG repeats). May have been confirmed historically or at Screening
• Weight ≥45 kg
• CGI-S score ≥4
• Is in general good health as deemed by the Investigator, determined by physical examination, medical history and laboratory tests
• If receiving sertraline, is on a stable, well-tolerated dose for the previous 3 months with no further changes anticipated
• Agrees not to discuss treatment outcomes on social media until subject has completed their End of Therapy visit

Exclusion Criteria:

• Active or history of peptic or gastric ulcer or hemorrhage
• Any chronic major medical comorbid condition deemed by the Investigator as presenting added risk to the subject, including but not limited to refractory hypertension, kidney disease, or liver disease
• Diagnosed with diabetes (Type 1 or II) or receiving any anti-diabetic medication
• Unstable seizure disorder defined by any seizure within 6 months prior to baseline visit and/or a change in any anti-convulsant drug dosing in the 60 days prior to study entry
• Patients with cardiovascular disease risk factors: Uncontrolled high blood pressure (systolic blood pressure >150 mmHg), Unstable angina, History of documented myocardial infarction or cerebrovascular accident, NYHA Class III and IV heart failure, Known uncontrolled hyperlipidemia as LDL-C ≥190 mg/dL or triglycerides ≥ 500 mg/dL
• Chronic use of NSAIDs or other anti-inflammatory agents
• Currently taking or have taken any cannabidiol (CBD) preparation within 30 days prior to screening
• Currently taking or have taken sulindac or gaboxadol within 30 days prior to screening
• Currently taking GABAergic agents (i.e., acamprosate, baclofen, vigabatrin, tiagabine, riluzole, benzodiazepines, and gabapentin)
• Changes in psychotropic or anti-convulsant (where taken for reasons other than seizure control) drug treatment within 30 days prior to Screening
• Significant changes in any educational, behavioral and/or dietary interventions the month prior to Screening
• Planned initiation of new, or modification of ongoing, interventions during the study
• History of adverse effects of sulindac or other NSAIDs that would prevent safe study completion
• Unable or unwilling to take oral medication (whole capsule) or history of dysphagia or malabsorption
• Has abnormal baseline laboratory assessments including, but not limited to, ALT or AST or total bilirubin >1.5 × ULN, or other clinically relevant laboratory abnormality
• Has a clinically significant abnormal ECG, heart rate or BP at Screening as judged by the Investigator
• Has received an investigational drug (either approved or not approved) in any prior clinical study within 30 days or 5 half-lives (whichever is longer) prior to Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; One capsule, twice a day	Drug: Placebo; Placebo Capsule
Active Comparator: Sulindac (HLX-0201), dose strength 1; One capsule, twice a day	Drug: Sulindac (HLX-0201), dose strength 1; Sulindac (HLX-0201) Capsule
Active Comparator: Sulindac (HLX-0201), dose strength 2; One capsule, twice a day	Drug: Sulindac (HLX-0201), dose strength 2; Sulindac (HLX-0201) Capsule
Active Comparator: Gaboxadol (HLX-0206); One capsule, twice a day	Drug: Gaboxadol (HLX-0206); Gaboxadol (HLX-0206) Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIH Cognitive Toolbox		Day 70
Clinical Global Impression - I		Day 70
Aberrant Behavior Checklist		Day 70
Anxiety, Depression, and Mood Scale		Day 70
FXS Domain Specific Concerns	The Clinician/Caregiver FXS Domain Specific Concerns allows for the subject specific symptoms of concern to be assessed on an ongoing basis throughout the study. The specific concerns that correlate to the 6 domains (Clinician) or 3 Domains (Caregiver) will be assessed using a 7-point Likert scale.	Day 70

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of each dose	Incidence of adverse events (AEs) and serious adverse events (SAEs) reported during the study. Change from baseline to Day 70 in physical examinations and assessment of vital signs.	Day 70
Kiddie Test of Attentional Performance (KiTAP)		Day 70
Emotional Faces Tobii Eye Tracking		Day 70
EEG	Resting state whole brain EEG spectra activity in 3 EEG assessments (EEG spectra, auditory evoked response potential (ERP) and Chirp modulated sweep.	Day 70
CGI-S		Day 70

Collaborators and Investigators

• Sponsor: Healx Limited
• Investigators: Principal Investigator: Elizabeth Berry-Kravis, Rush University Medical Center & Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Fragile X Syndrome; FXS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; GABA Agents; Anticonvulsants; GABA Agonists; Sulindac; Gaboxadol
• Other Study ID Numbers: HLX002-0201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No