A Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome

Study Overview
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Brief Summary
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A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) with Fragile X Syndrome

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: BPN14770/ zatolmilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subject aged 18 to 45 years at screening visit. Subject has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1)mutation (≥200 CGG repetitions). Subject is able to swallow capsules. Current treatment with ≤3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for the treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 4 weeks prior to screening and must remain stable during the period between screening and the commencement of the study treatment. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to screening and must remain stable during the period between screening and commencement of the study treatment. Subjects with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure free for 3 months preceding screening or must be seizure free for 2 years if not currently receiving anti-epileptics. Behavioral and other non-pharmacological treatments/interventions must be stable for 4 weeks prior to screening and must remain stable during the period between screening and first dose of study treatment and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a program (eg, due to a vacation) are allowed. Subject must be willing to practice barrier methods of contraception while on the study if sexually active. Abstinence is also considered a reasonable form of birth control in this study population. Subject has a parent, legal authorized guardian, or consistent caregiver. Subject and caregiver are able to attend the clinic regularly and reliably. If subject is his own legal guardian, he is able to understand and sign informed consent to participate in the study. For subjects who are not their own legal guardian, subject's parent/legally authorized guardian is able to understand and sign an informed consent form for their child to participate in the study. If subject is not his own legal guardian, subject must provide assent for participation in the study if he has the cognitive ability to do so. Exclusion Criteria: Inability to successfully complete the NIH-TCB picture vocabulary and oral reading assessments at screening and baseline. The ability to complete the NIH-TBC oral reading and picture vocabulary subtest at baseline is defined as the ability to complete both subtests, with (1) confirmation from the clinician administering that the test administrations are valid (noted on the administration form) and (2) generation of valid test scores for each test. History of or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the subject at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study treatment. a. Common conditions such as mild hypertension, etc. are allowed per the principal investigator's judgement as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization. Renal impairment, defined as serum creatinine > 1.25 × ULN at screening Hepatic impairment, defined as ALT or AST elevation > 2 × ULN at screening. Note: LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs remain elevated, the subject is ineligible to participate. Clinically significant abnormalities, in the investigator's judgement, in safety laboratory tests, vital signs, or ECG, as measured during screening. History of substance abuse within the past year, according to investigator assessment. Positive COVID-19 test during screening. Significant hearing or visual impairment that may affect the subject's ability to complete the test procedures. Concurrent major psychiatric condition (eg, major depressive disorder, schizophrenia, or bipolar disorder) as diagnosed by the investigator. Subjects with the additional diagnosis of autism spectrum disorder or anxiety disorder will be allowed. Subject has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis. Subject is planning to commence psychotherapy or cognitive behavior therapy during the period of the study or had begun psychotherapy or cognitive behavior therapy within 4 weeks prior to screening. Subject is an immediate family member of anyone employed by the sponsor, investigator, or study staff. Subject has a body mass index of less than 18 kg/m2 or greater than 36 kg/m2. Subject has participated in another clinical trial within the 30 days preceding Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Drug<br>25mg BID BPN14770 | Drug: BPN14770/ zatolmilast<br>* 25mg BID BPN14770<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC) | National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC), which is calculated from the Picture Vocabulary and Oral Reading domains. | 13 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical rating scale (NRS) scores based on subject-specific behaviors vs baseline | Numerical rating scale (NRS) scores based on subject-specific behaviors within the domains of Daily Function and Language | 13 Weeks | 
| Caregiver Global Impression of Improvement (CaGI-I) | Caregiver Global Impression of Improvement (CaGI-I) for the general domains of Daily Function and Language | 13 Weeks | 
| Clinical Global Impression Improvement (CGI-I) for - Investigator | Clinical Global Impression Improvement (CGI-I) for - Investigator rated the general domains of Daily Function and Language | 13 Weeks | 
| Vineland-3 Adaptive Behavior Scale (Vineland-3) | Vineland-3 Adaptive Behavior Scale (Vineland-3), using the composite score and domain scores from communication, daily living skills, and socialization | 13 Weeks | 
| Verbal Knowledge test from the Stanford-Binet (ed 5) (SB-5)IQ | Verbal Knowledge test from the Stanford-Binet (ed 5) (SB-5) IQ assessment | 13 Weeks | 
| NIH-TCB domains of Picture Sequence Memory, Flanker Inhibitory Control and Attention, List Sorting Working Memory, Dimensional Change Card Sort, and Speeded Matching | NIH-TCB domains of Picture Sequence Memory, Flanker Inhibitory Control and Attention, List Sorting Working Memory, Dimensional Change Card Sort, and Speeded Matching | 13 Weeks | 
| Aberrant Behavior Checklist (ABC) scores | Aberrant Behavior Checklist (ABC) scores | 13 Weeks | 
| Anxiety, Depression, and Mood Scale (ADAMS) scores | Anxiety, Depression, and Mood Scale (ADAMS) scores | 13 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FXS