Fragile X SyndromePhase 2/3NCT05163808
A Randomized Study of BPN14770 in Male Adolescents (Aged 9 to < 18 Years) With Fragile X Syndrome
A Phase 2/3 study testing zatolmilast in people with Fragile X Syndrome, run by Tetra Discovery Partners at 17 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 9 to 18 years, men only
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- zatolmilast
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 163 participants
- Where
- 17 sitesUnited States
- Study dates
- 29 Mar 2022to 2 Sep 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
- 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.
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- 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.
- 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.
- 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.
- Patient Exclusion Criteria
- 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.
- Common conditions such as mild hypertension, etc. are allowed per the PI'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 × ULN at screening.
- Cirrhosis, unstable chronic liver disease or acute liver disease. Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase elevation > 2 × ULN at screening. Note: liver function tests may be repeated after 1 week to evaluate return to acceptable limits; if liver function tests remain elevated, patient is ineligible to participate. Subjects with stable chronic hepatitis B on oral anti-viral therapy and subjects cured of chronic hepatitis C may be allowed. Subjects with Gilbert syndrome are allowed.
- Clinically significant abnormalities, in the PI's judgment, in safety laboratory tests, vital signs, or 12-lead ECG, as measured during screening.
- History of alcohol abuse at any time in life or history of other substance abuse within the past year, according to PI's assessment.
- Significant hearing or visual impairment that may affect the patient's ability to complete the test procedures.
- Concurrent major psychiatric condition (eg, major depressive disorder, schizophrenia, or bipolar disorder) as confirmed by the PI. Patients 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 CBT within 4 weeks prior to screening.
- Patient is an immediate family member of anyone employed by the sponsor, PI, or study staff.
- Patient has weight < 25 kg or a BMI greater than the 97th percentile for his age according to the Centers for Disease Control and Prevention (refer to Appendix 1). To participate in the Part 1 cohort receiving 50 mg dose, patient must weigh ≥ 75 lbs (34 kg).
- Patient has participated in another clinical trial within the 30 days before screening.
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Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Boston Children's Hospital
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinatti Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Greenwood Genetic Center
Greenville, South Carolina, 29605
Amnova Clinical Research
Irvine, California, 92604
University of Kansas Medical Center
Kansas City, Kansas, 66160
Suburban Research Associates
Media, Pennsylvania, 19063
University of Miami
Miami, Florida, 33136
Icahn School of Medicine at Mount Sinai Hospital
New York, New York, 10029
Thompson Autism & Neurodevelopment Center - CHOC
Orange, California, 92868
UC Davis
Sacramento, California, 95817
University of Utah and Primary Childrens Hospital
Salt Lake City, Utah, 84113
Clinic for Special Children
Strasburg, Pennsylvania, 17579
U Mass
Worcester, Massachusetts, 01655
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Two-Part Study of BPN14770 in Male Adolescents (Aged 9 to < 18 Years) With Fragile X Syndrome
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).
Read the 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.
- Conditions
- Fragile X Syndrome
- Being tested
- zatolmilast, Placebo
- Medical subject headings
- Fragile X Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zatolmilastDrug
Also called BPN14770
Subjects will receive a 15 mg or 25 mg dose of zatolmilast (BPN14770) or placebo
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Study Drug | Active comparator | Subjects will receive 15 mg BID or 25mg BID dose of BPN14770 Receives: Drug: zatolmilast |
| Placebo Arm | Placebo comparator | Subjects will receive matching Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 13 Weeks
Secondary outcomes (8)
NRS patient-specific behaviors within the domains of Daily Function, Language, and Academic Skills.
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.
Measured: 13 Weeks
CaGI-I for the general domains of Daily Function, Language, and Academic Skills.
Change from baseline to Week 13 Caregiver Global Impression of Improvement (CaGI-I) for the general domains of Daily Function, Language, and Academic Skills.
Measured: 13 Weeks
Investigator rated (CGI-I) for the general domains of Daily Function, Language, and Academic Skills
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
Measured: 13 Weeks
NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors
Change from baseline to Week 13 NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors
Measured: 13 Weeks
CaGI-I for the general domain of Emotions/Behaviors
Change from baseline to Week 13 CaGI-I for the general domain of Emotions/Behaviors
Measured: 13 Weeks
The NIH-TCB domains of Picture Vocabulary, Oral Reading Recognition, and Pattern Comparison Processing Speed
Change from baseline to Week 13 the NIH-TCB domains of Picture Vocabulary, Oral Reading Recognition, and Pattern Comparison Processing Speed
Measured: 13 Weeks
Vineland-3 Adaptive Behavior Scale (Vineland-3)
Change from baseline to Week 13 Vineland-3 Adaptive Behavior Scale (Vineland-3)
Measured: 13 Weeks
Verbal Knowledge test from the Stanford Binet (ed 5) (SB-5) IQ assessment
Change from baseline Verbal Knowledge test from the Stanford Binet (ed 5) (SB-5) IQ assessment
Measured: 13 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2021
- Study start29 Mar 2022
- Primary completion2 Sep 2025
- Study completion2 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2 treatment Groups (Study Drug and Placebo)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tetra Discovery Partners
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05163808
- Sponsor's protocol ID
- BPN14770-CNS-204
- Status last verified
- Apr 2026
- First submitted
- 15 Dec 2021
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Two-Part Study of BPN14770 in Male Adolescents (Aged 9 to < 18 Years) With Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT05163808
- Acronym / sponsor ID
- BPN14770-CNS-204
- Conditions
- Fragile X Syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Tetra Discovery PartnersIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2022 (actual)
- Primary completion
- 2 Sep 2025 (actual)
- Study completion
- 2 Sep 2025 (actual)
- First posted
- 20 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2 treatment Groups (Study Drug and Placebo)
| Arm | Type | Receives |
|---|---|---|
| Study Drug | Active comparator | Drug: zatolmilastSubjects will receive 15 mg BID or 25mg BID dose of BPN14770 |
| Placebo Arm | Placebo comparator | Drug: PlaceboSubjects will receive matching Placebo |
Who may qualify
- Ages
- 9 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (32 listed)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zatolmilastAlso: BPN14770Subjects will receive a 15 mg or 25 mg dose of zatolmilast (BPN14770) or placebo | Drug | Study Drug |
| PlaceboPlacebo | Drug | Placebo Arm |
Primary outcome
NIH Toolbox Cognitive Battery cognition crystallized composite score
Time frame: 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.
8 secondary outcomes
NRS patient-specific behaviors within the domains of Daily Function, Language, and Academic Skills.
Time frame: 13 Weeks
CaGI-I for the general domains of Daily Function, Language, and Academic Skills.
Time frame: 13 Weeks
Investigator rated (CGI-I) for the general domains of Daily Function, Language, and Academic Skills
Time frame: 13 Weeks
NRS scores based on patient-specific behaviors within the domain of Emotions/Behaviors
Time frame: 13 Weeks
CaGI-I for the general domain of Emotions/Behaviors
Time frame: 13 Weeks
The NIH-TCB domains of Picture Vocabulary, Oral Reading Recognition, and Pattern Comparison Processing Speed
Time frame: 13 Weeks
Vineland-3 Adaptive Behavior Scale (Vineland-3)
Time frame: 13 Weeks
Verbal Knowledge test from the Stanford Binet (ed 5) (SB-5) IQ assessment
Time frame: 13 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing zatolmilast in people with Fragile X Syndrome, run by Tetra Discovery Partners at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NIH Toolbox Cognitive Battery cognition crystallized composite score (time frame: 13 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.