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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: Sulindac (HLX-0201), dose strength 1
* Drug: Sulindac (HLX-0201), dose strength 2
* Drug: Placebo
* Drug: Gaboxadol (HLX-0206)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FXS, Fragile X Syndrome