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

NCT04823052 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HLX002-0201
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

Fragile X Syndrome

Keywords

Fragile X Syndrome; FXS

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (5)

• To assess the safety and tolerability of each dose

  Day 70

• Kiddie Test of Attentional Performance (KiTAP)

  Day 70

• Emotional Faces Tobii Eye Tracking

  Day 70

• EEG

  Day 70

• CGI-S

  Day 70

Study Arms (4)

Placebo

PLACEBO COMPARATOR

One capsule, twice a day

Drug: Placebo

Sulindac (HLX-0201), dose strength 1

ACTIVE COMPARATOR

One capsule, twice a day

Drug: Sulindac (HLX-0201), dose strength 1

Sulindac (HLX-0201), dose strength 2

ACTIVE COMPARATOR

One capsule, twice a day

Drug: Sulindac (HLX-0201), dose strength 2

Gaboxadol (HLX-0206)

ACTIVE COMPARATOR

One capsule, twice a day

Drug: Gaboxadol (HLX-0206)

Interventions

Sulindac (HLX-0201), dose strength 1 DRUG

Sulindac (HLX-0201) Capsule

Sulindac (HLX-0201), dose strength 1

Sulindac (HLX-0201), dose strength 2 DRUG

Sulindac (HLX-0201) Capsule

Sulindac (HLX-0201), dose strength 2

Placebo DRUG

Placebo Capsule

Placebo

Gaboxadol (HLX-0206) DRUG

Gaboxadol (HLX-0206) Capsule

Gaboxadol (HLX-0206)

Eligibility Criteria

• Age: 13 Years - 40 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Healx Limited: lead

Study Sites (10)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center & Children's Hospital

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Insitute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 10655, United States

Location

Icahn School of Medicine (Mount Sinai)

New York, New York, 10029, United States

Location

Children's Health Queensland Hospital and Health Service

Brisbane, Queensland, 4101, Australia

Location

Fragile X Alliance Clinic

Caulfield, Victoria, 3161, Australia

Location

Murdoch Children's Research Institute

Melbourne, Victoria, 3052, Australia

Location

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Sulindac; gaboxadol

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Elizabeth Berry-Kravis

  Rush University Medical Center & Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Subjects will be randomly assigned to 1 of 4 treatment arms. All treatment arms will be conducted in parallel. Fifteen subjects will be included in each arm. The study treatment will be blinded to patients, carers and physicians.

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: March 30, 2021
• Study Start: May 25, 2022
• Primary Completion: October 19, 2022
• Study Completion: October 19, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-12

Locations

US (7); AU (3)