A 2-Period Crossover Study of BPN14770 in Adults Males With Fragile X Syndrome

NCT03569631 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BPN14770-CNS-203
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, double-blind, 2-period crossover study to explore the effects of BPN14770 on cognitive function and behavior in subjects with Fragile X Syndrome. Subjects will receive both active treatment with BPN14770 capsules and matching placebo capsules in the course of the study. One treatment will be administered during each of the 12-week study periods.

Conditions

Fragile X Syndrome; FXS; Fra(X) Syndrome

Keywords

Phosphodiesterase Type 4D; PDE4D; Cognitive Dysfunction; Neurocognitive Disorders; Fragile X Syndrome; Fragile X; FXS; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Cognition Disorders; Enzyme Inhibitors; Nootropic Agents; Developmental Disorder; Autism; Autistic Spectrum Disorder; Genetic Disease; Behavioral Disorder; Learning Disorder

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  A TEAE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A Serious Adverse Event (SAE) was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

  Up to 24 weeks

Secondary Outcomes (3)

• Change From Baseline in National Institute of Health Toolbox Cognitive Battery Modified for Intellectual Disabilities Crystallized Cognition Composite (NIH-TCB CCC) Score

  Baseline to Week 12

• Change From Baseline Between BPN14770 and Placebo Arm in Visual Analog Scale (VAS) Daily Functioning

  Baseline to Week 12

• Change From Baseline Between BPN14770 and Placebo Arm in VAS Language

  Baseline to Week 12

Study Arms (2)

BPN14770

EXPERIMENTAL

25mg BPN14770 capsules, one capsule taken twice daily for 12 weeks

Drug: BPN14770

Placebo

PLACEBO COMPARATOR

Matching placebo capsules, one capsule taken twice daily for 12 weeks

Drug: Placebo

Interventions

BPN14770 DRUG

25 mg BPN14770 capsules

BPN14770

Placebo DRUG

Placebo capsules to mimic 25 mg BPN14770 capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is male aged 18 to 45 years, inclusive.
• Subject has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repetitions).
• Current treatment with no more than 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 2 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
• 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 the commencement of study medication.
• 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 3 years if not currently receiving anti-epileptics.
• Subject 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.
• Subject has a parent, legal authorized guardian or consistent caregiver.
• Subject and caregiver are able to attend the clinic regularly and reliably.
• Subject is able to swallow tablets and capsules.
• For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study.
• If subject is his/her own legal guardian, he/she can understand and sign informed consent to participate in the study.
• If subject is not their own legal guardian, the subject provides assent for participation in the study, if the subject has the cognitive ability to provide assent.

You may not qualify if:

• 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 medication. Common diseases such as mild hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C \[Hgb A1C\] \<6.5%), etc. are allowed per the investigator's judgment 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 x ULN at screening
• Hepatic impairment, defined as ALT or AST elevation \> 2 x ULN at screening. Note:
• LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs remain elevated, subject is ineligible to participate.
• Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, or ECG, as measured during Screening.
• History of substance abuse within the past year, according to investigator assessment.
• Significant hearing or visual impairment that may affect the subject's ability to complete the test procedures.
• Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Subjects with 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 (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening.
• Subject is related to anyone employed by the sponsor, investigator, or study staff.
• Subject has BMI less than 18 or greater than 36.
• Subject has participated in another clinical trial within the 30 days preceding Screening.

Sponsors & Collaborators

• Tetra Discovery Partners: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• Gurney ME, Cogram P, Deacon RM, Rex C, Tranfaglia M. Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D). Sci Rep. 2017 Nov 7;7(1):14653. doi: 10.1038/s41598-017-15028-x.

  PMID: 29116166 BACKGROUND

• Berry-Kravis EM, Harnett MD, Reines SA, Reese MA, Ethridge LE, Outterson AH, Michalak C, Furman J, Gurney ME. Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat Med. 2021 May;27(5):862-870. doi: 10.1038/s41591-021-01321-w. Epub 2021 Apr 29.

  PMID: 33927413 DERIVED

MeSH Terms

Conditions

Fragile X Syndrome; Cognitive Dysfunction; Neurocognitive Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Cognition Disorders; Developmental Disabilities; Autistic Disorder; Autism Spectrum Disorder; Genetic Diseases, Inborn; Learning Disabilities

Interventions

BPN14770

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Communication Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Shionogi Clinical Trials Administrator Clinical Support Help Line
• Organization: Shionogi

Shionogiclintrials-admin@shionogi.co.jp

1-800-849-9707

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 26, 2018
• Study Start: July 9, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: December 19, 2024
• Results First Posted: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)