A Randomized Study of BPN14770 in Male Adolescents (Aged 9 to < 18 Years) With Fragile X Syndrome

NCT05163808 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: BPN14770-CNS-204
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 17

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).

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (1)

• NIH Toolbox Cognitive Battery cognition crystallized composite score

  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.

  13 Weeks

Secondary Outcomes (8)

• NRS patient-specific behaviors within the domains of Daily Function, Language, and Academic Skills.

  13 Weeks

• CaGI-I for the general domains of Daily Function, Language, and Academic Skills.

  13 Weeks

• Investigator rated (CGI-I) for the general domains of Daily Function, Language, and Academic Skills

  13 Weeks

• NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors

  13 Weeks

• CaGI-I for the general domain of Emotions/Behaviors

  13 Weeks

Study Arms (2)

Study Drug

ACTIVE COMPARATOR

Subjects will receive 15 mg BID or 25mg BID dose of BPN14770

Drug: zatolmilast

Placebo Arm

PLACEBO COMPARATOR

Subjects will receive matching Placebo

Drug: Placebo

Interventions

zatolmilast DRUG

Subjects will receive a 15 mg or 25 mg dose of zatolmilast (BPN14770) or placebo

Also known as: BPN14770

Study Drug

Placebo DRUG

Placebo

Placebo Arm

Eligibility Criteria

• Age: 9 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. 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).
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. Patient has a parent(s), legal authorized guardian(s), or consistent caregiver(s).
• \. 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.
• \. Patient must provide assent for participation in the study if the patient has the cognitive ability to provide assent.
• \. To participate in the Part 1 PK only: subjects must be able to swallow capsules.

You may not qualify if:

• 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 is male adolescent aged 12 to \< 18 years.
• Patient has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1) mutation (≥ 200 CGG repetitions).
• 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.
• 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.
• 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.
• 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.
• 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.
• Patient has a parent(s), legal authorized guardian(s), or consistent caregiver(s).
• Patient and caregiver are able to attend the clinic regularly and reliably.
• 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.
• Patient must provide assent for participation in the study if the patient has the cognitive ability to provide assent.
• To participate in the Part 1 PK only: patients must be able to swallow capsules.
• Inability to successfully complete the NIH-TCB picture vocabulary and oral reading assessments at screening and baseline for Part 2 (DB). Patient must be able to complete these assessments at baseline to be randomized into Part 2; care should be taken that a patient enrolled into Part 1 (PK) possesses this ability if their desire is to continue to Part 2. 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 patient at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study drug.

Sponsors & Collaborators

• Tetra Discovery Partners: lead

Study Sites (17)

Amnova Clinical Research

Irvine, California, 92604, United States

Location

Thompson Autism & Neurodevelopment Center - CHOC

Orange, California, 92868, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

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

Chicago, Illinois, 60612, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

U Mass

Worcester, Massachusetts, 01655, United States

Location

Icahn School of Medicine at Mount Sinai Hospital

New York, New York, 10029, United States

Location

Cincinatti Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Clinic for Special Children

Strasburg, Pennsylvania, 17579, United States

Location

Greenwood Genetic Center

Greenville, South Carolina, 29605, United States

Location

University of Utah and Primary Childrens Hospital

Salt Lake City, Utah, 84113, United States

Location

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

BPN14770

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

Study Design

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

Model Details: 2 treatment Groups (Study Drug and Placebo)

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: December 20, 2021
• Study Start: March 29, 2022
• Primary Completion: September 2, 2025
• Study Completion: September 2, 2025
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)