Clinical trial NCT04823052: Investigation of Sulindac (HLX-0201) and Gaboxadol (HLX-0206) in Male Fragile X Syndrome Patients Aged 13-40
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Fragile X Syndrome
Keywords: Fragile X Syndrome
FXS
Lead sponsor: Healx Limited
Sponsor class: INDUSTRY
First posted: 2021-03-30
Enrollment: 0
Sex: MALE
Minimum age (years): 13
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: NIH Cognitive Toolbox
timeFrame: Day 70
measure: Clinical Global Impression - I
timeFrame: Day 70
measure: Aberrant Behavior Checklist
timeFrame: Day 70
measure: Anxiety, Depression, and Mood Scale
timeFrame: Day 70
measure: FXS Domain Specific Concerns
timeFrame: Day 70
Secondary outcomes:
measure: To assess the safety and tolerability of each dose
timeFrame: Day 70
measure: Kiddie Test of Attentional Performance (KiTAP)
timeFrame: Day 70
measure: Emotional Faces Tobii Eye Tracking
timeFrame: Day 70
measure: EEG
timeFrame: Day 70
measure: CGI-S
timeFrame: Day 70
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center & Children's Hospital
state: Illinois
city: Baltimore
country: United States
facility: Kennedy Krieger Insitute
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine (Mount Sinai)
state: New York
city: Brisbane
country: Australia
facility: Children's Health Queensland Hospital and Health Service
state: Queensland
city: Caulfield
country: Australia
facility: Fragile X Alliance Clinic
state: Victoria
city: Melbourne
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
Study officials:
affiliation: Rush University Medical Center & Children's Hospital
name: Elizabeth Berry-Kravis
role: PRINCIPAL_INVESTIGATOR
References: