Fragile X Syndrome
Conditions
Brief summary
This is a 2-part study, with each part having a unique set of objectives for male adolescents aged 9 to \< 18 years with fragile X syndrome (FXS). Part 1 is an open-label, single-dose, pharmacokinetics (PK) assessment of BPN14770 25 mg and 50 mg, while Part 2 is double-blind (DB) and randomized between two treatment groups (Study Drug and Placebo).
Detailed description
In amendment 4 the enrollment age range what changed to allow enrollment in participants as young as 9 years of age. This only affects Part 2 as Part 1 was completed prior to this amendment.
Interventions
DRUGzatolmilast
Subjects will receive a 15 mg or 25 mg dose of zatolmilast (BPN14770) or placebo
DRUGPlacebo
Placebo
Sponsors
Tetra Discovery Partners
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Intervention model description
2 treatment Groups (Study Drug and Placebo)
Eligibility
Sex/Gender
MALE
Age
9 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Patient is male adolescent aged 9 to \< 18 years. 2. Patient has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1) mutation (≥ 200 CGG repetitions). 3\. Current treatment with ≤ 3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. If the subject is on 3 prescribed psychoactive medications and, in addition, is taking either a psychoactive over-the-counter medication (eg, melatonin, Benadryl, etc.) or CBD products, the investigator is encouraged to discuss eligibility with the medical monitor. 4\. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 4 weeks before screening and must remain stable during the period between screening and the commencement of study drug. Every effort should be made to keep dosing stable throughout the study. 5\. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks before screening and must remain stable during the period between screening and the commencement of study drug. Every effort should be made to keep dosing stable throughout the study. 6\. Patients with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months before screening or must be seizure-free for 2 years if not currently receiving anti-epileptics. 7\. Behavioral and other non-pharmacological treatments/interventions must be stable for 4 weeks before screening and must remain stable during the period between screening and the commencement of study drug, 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 school program, due to school vacations, are allowed. 8\. Patient must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population. 9\. Patient has a parent(s), legal authorized guardian(s), or consistent caregiver(s). 10\. Patient and caregiver are able to attend the clinic regularly and reliably. 11. Patient's parent(s), legal authorized guardian(s), or consistent caregiver(s) is able to understand and sign an informed consent form to participate in the study. 12\. Patient must provide assent for participation in the study if the patient has the cognitive ability to provide assent. 13\. To participate in the Part 1 PK only: subjects must be able to swallow capsules.
Exclusion criteria
Diagnosis and main criteria for inclusion: The eligibility criteria are the same for all parts of the study except for Part 1 (PK), where patients must be able to swallow capsules and must weigh at least 75 lbs (34 kg) to receive the 50 mg dose. Patient Inclusion Criteria 1. Patient is male adolescent aged 12 to \< 18 years. 2. Patient has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1) mutation (≥ 200 CGG repetitions). 3. Current treatment with ≤ 3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. 4. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 4 weeks before screening and must remain stable during the period between screening and the commencement of study drug. 5. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks before screening and must remain stable during the period between screening and the commencement of study drug. 6. Patients with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months before screening or must be seizure-free for 2 years if not currently receiving anti-epileptics. 7. Behavioral and other non-pharmacological treatments/interventions must be stable for 4 weeks before screening and must remain stable during the period between screening and the commencement of study drug, 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 school program, due to school vacations, are allowed. 8. Patient must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population. 9. Patient has a parent(s), legal authorized guardian(s), or consistent caregiver(s). 10. Patient and caregiver are able to attend the clinic regularly and reliably. 11. Patient's parent(s), legal authorized guardian(s), or consistent caregiver(s) is able to understand and sign an informed consent form to participate in the study. 12. Patient must provide assent for participation in the study if the patient has the cognitive ability to provide assent. 13. To participate in the Part 1 PK only: patients must be able to swallow capsules. Patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NIH Toolbox Cognitive Battery cognition crystallized composite score | 13 Weeks | The change from baseline to Week 13 in the NIH Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC), which is calculated from the Picture Vocabulary and Oral Reading domains. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NRS patient-specific behaviors within the domains of Daily Function, Language, and Academic Skills. | 13 Weeks | Change from baseline to Week 13 in Numerical rating scale (NRS) scores based on patient-specific behaviors within the domains of Daily Function, Language, and Academic Skills. |
| CaGI-I for the general domains of Daily Function, Language, and Academic Skills. | 13 Weeks | Change from baseline to Week 13 Caregiver Global Impression of Improvement (CaGI-I) for the general domains of Daily Function, Language, and Academic Skills. |
| Investigator rated (CGI-I) for the general domains of Daily Function, Language, and Academic Skills | 13 Weeks | Change from baseline to Week 13 Clinical Global Impression Improvement - Investigator rated (CGI-I) for the general domains of Daily Function, Language, and Academic Skills |
| NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors | 13 Weeks | Change from baseline to Week 13 NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors |
| CaGI-I for the general domain of Emotions/Behaviors | 13 Weeks | Change from baseline to Week 13 CaGI-I for the general domain of Emotions/Behaviors |
| The NIH-TCB domains of Picture Vocabulary, Oral Reading Recognition, and Pattern Comparison Processing Speed | 13 Weeks | Change from baseline to Week 13 the NIH-TCB domains of Picture Vocabulary, Oral Reading Recognition, and Pattern Comparison Processing Speed |
| Vineland-3 Adaptive Behavior Scale (Vineland-3) | 13 Weeks | Change from baseline to Week 13 Vineland-3 Adaptive Behavior Scale (Vineland-3) |
| Verbal Knowledge test from the Stanford Binet (ed 5) (SB-5) IQ assessment | 13 Weeks | Change from baseline Verbal Knowledge test from the Stanford Binet (ed 5) (SB-5) IQ assessment |
Countries
United States
Outcome results
None listed