Clinical trial NCT05358886: A Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Fragile X Syndrome
Keywords: FXS
Lead sponsor: Tetra Discovery Partners
Sponsor class: INDUSTRY
First posted: 2022-05-03
Enrollment: 171
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Male subject aged 18 to 45 years at screening visit.
2. Subject has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1)mutation (≥200 CGG repetitions).
3. Subject is able to swallow capsules.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Subject has a parent, legal authorized guardian, or consistent caregiver.
11. Subject and caregiver are able to attend the clinic regularly and reliably.
12. If subject is his own legal guardian, he is able to understand and sign informed consent to participate in the study.
13. 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.
14. 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:

1. 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.
2. 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.
3. Renal impairment, defined as serum creatinine \> 1.25 × ULN at screening
4. 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.
5. Clinically significant abnormalities, in the investigator's judgement, in safety laboratory tests, vital signs, or ECG, as measured during screening.
6. History of substance abuse within the past year, according to investigator assessment.
7. Positive COVID-19 test during screening.
8. Significant hearing or visual impairment that may affect the subject's ability to complete the test procedures.
9. 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.
10. Subject has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.
11. 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.
12. Subject is an immediate family member of anyone employed by the sponsor, investigator, or study staff.
13. Subject has a body mass index of less than 18 kg/m2 or greater than 36 kg/m2.
14. Subject has participated in another clinical trial within the 30 days preceding Screening

Primary outcomes:
measure: National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC)
timeFrame: 13 Weeks
Secondary outcomes:
measure: Numerical rating scale (NRS) scores based on subject-specific behaviors vs baseline
timeFrame: 13 Weeks
measure: Caregiver Global Impression of Improvement (CaGI-I)
timeFrame: 13 Weeks
measure: Clinical Global Impression Improvement (CGI-I) for - Investigator
timeFrame: 13 Weeks
measure: Vineland-3 Adaptive Behavior Scale (Vineland-3)
timeFrame: 13 Weeks
measure: Verbal Knowledge test from the Stanford-Binet (ed 5) (SB-5)IQ
timeFrame: 13 Weeks
measure: NIH-TCB domains of Picture Sequence Memory, Flanker Inhibitory Control and Attention, List Sorting Working Memory, Dimensional Change Card Sort, and Speeded Matching
timeFrame: 13 Weeks
measure: Aberrant Behavior Checklist (ABC) scores
timeFrame: 13 Weeks
measure: Anxiety, Depression, and Mood Scale (ADAMS) scores
timeFrame: 13 Weeks
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Amnova Clinical Research
state: California
city: Orange
country: United States
facility: Thompson Autism & Neurodevelopment Center - CHOC
state: California
city: Sacramento
country: United States
facility: UC Davis Health System
state: California
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
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Strasburg
country: United States
facility: Clinic for Special Children
state: Pennsylvania
city: Greenville
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah and Primary Childrens Hospital
state: Utah
Study officials:
affiliation: Rush Medical Center
name: Elizabeth Berry-Kravis, MD
role: PRINCIPAL_INVESTIGATOR
References: