BPN14770 for Fragile X Syndrome

No longer recruiting at 25 trial locations

Overseen By CEO

Age: 18 - 65

Sex: Male

Trial Phase: Phase 3

Sponsor: Tetra Discovery Partners

Disqualifiers: Renal impairment, Hepatic impairment, Substance abuse, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BPN14770 (also known as zatolmilast) for Fragile X Syndrome, a genetic condition affecting brain development and function. The study compares BPN14770 to a placebo (a harmless pill with no active drug) to determine if it improves symptoms in participants. It seeks male adults diagnosed with Fragile X Syndrome who are currently taking no more than three psychotropic medications. The goal is to determine if BPN14770 can be a safe and effective treatment option for those affected by this condition. Participants must be able to swallow capsules and have stable medication and therapy plans before joining. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial allows participants to continue taking up to three prescribed psychotropic medications, as long as the doses have been stable for at least 4 weeks before the screening and remain stable during the study. Anti-epileptic medications are also allowed if they are stable for 12 weeks before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BPN14770, also known as zatolmilast, was safe in earlier studies. A recent trial with this drug found no major safety issues. Participants tolerated the treatment well, experiencing few serious side effects. However, zatolmilast is still under investigation, and its safety and effectiveness for Fragile X Syndrome have not been officially proven. More research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Fragile X Syndrome?

Unlike the standard treatments for Fragile X Syndrome, which often include medications like antipsychotics and stimulants to manage symptoms, BPN14770 (zatolmilast) offers a new approach by targeting the enzyme phosphodiesterase-4D (PDE4D). This mechanism is unique because it aims to enhance cognitive function and synaptic plasticity directly, potentially leading to improvements in learning and memory. Researchers are excited about BPN14770 because it represents a shift from merely managing symptoms to potentially addressing the underlying neurological issues in Fragile X Syndrome. This could mean a significant improvement in quality of life for those affected.

What evidence suggests that BPN14770 might be an effective treatment for Fragile X Syndrome?

Research has shown that BPN14770, also known as zatolmilast, might help treat Fragile X syndrome. Studies suggest this drug could improve cognitive skills such as language and vocabulary. It may also aid in daily activities and behavior. BPN14770 blocks a specific enzyme, which is believed to enhance brain function. In this trial, participants will receive either BPN14770 or a placebo. Early results indicated that BPN14770 is generally well tolerated, with no major side effects compared to a placebo. ^{3 4 5 6 7}

Who Is on the Research Team?

Elizabeth Berry-Kravis, MD, PhD

Principal Investigator

Rush Medical Center

Are You a Good Fit for This Trial?

This trial is for male adults aged 18 to 45 with Fragile X Syndrome who can swallow capsules and have stable medication regimens. They must not be participating in other trials, have significant diseases or impairments that could affect results, or a history of substance abuse within the last year. If sexually active, they should use barrier contraception.

Inclusion Criteria

I have Fragile X Syndrome confirmed by a genetic test.

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

Subject and caregiver are able to attend the clinic regularly and reliably

Exclusion Criteria

I am starting or have recently started psychotherapy or cognitive behavior therapy.

I do not have active conditions like AIDS, hepatitis B, hepatitis C, or tuberculosis.

My liver tests are more than twice the normal limit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 25mg BID BPN14770 or placebo for 13 weeks

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BPN14770/ zatolmilast
• Placebo

Trial Overview The study tests BPN14770 (zatolmilast), comparing it against a placebo in a randomized, double-blind setup. Participants won't know if they're getting the actual drug or a dummy pill as researchers observe its effects on males with Fragile X Syndrome.

How Is the Trial Designed?

Group I: Study Drug Active Control 1 Intervention

25mg BID BPN14770

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Tetra Discovery Partners

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

In a randomized, double-blind, placebo-controlled crossover study involving 21 males with Fragile X syndrome, folinic acid therapy did not show statistically significant improvements in functioning compared to placebo, despite some parents reporting perceived benefits during the treatment phase.

No significant side effects were observed from long-term folinic acid therapy, leading researchers to offer a 3-month trial of the medication to all Fragile X patients, indicating a potential for safe use even if efficacy remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. Strom, CM., Brusca, RM., Pizzi, WJ.[2013]

In a pilot study involving 12 adults with fragile X syndrome, fenobam, an mGluR5 antagonist, was found to be safe with no significant adverse reactions reported after a single oral dose of 50-150 mg.

The study showed that 50% of participants experienced a notable improvement in sensory gating (measured by prepulse inhibition), suggesting potential efficacy, although the continuous performance test did not show significant improvement due to ceiling effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. Berry-Kravis, E., Hessl, D., Coffey, S., et al.[2022]

In two phase 2b clinical trials involving 175 adults and 139 adolescents with Fragile X syndrome, the mGluR5 antagonist mavoglurant did not show significant improvement in behavioral symptoms after 12 weeks of treatment, failing to confirm previous findings.

The safety profile of mavoglurant was consistent with earlier studies, showing few adverse events, but the trials indicated that the methylation status of the FMR1 gene did not predict treatment efficacy, suggesting a need for further research in younger populations and with different assessment markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Berry-Kravis, E., Des Portes, V., Hagerman, R., et al.[2016]

Mavoglurant, a drug targeting metabotropic glutamate receptor subtype-5, was found to be well tolerated in a long-term study with 267 participants (119 adolescents and 148 adults) over up to 34 months, showing no new safety concerns.

While the drug did not show significant behavioral benefits in initial studies, gradual improvements were noted in the open-label extensions, suggesting that further research is needed to explore its efficacy in treating Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. Hagerman, R., Jacquemont, S., Berry-Kravis, E., et al.[2019]

In a phase II study involving 134 adolescent patients with fragile X syndrome, mavoglurant did not show a significant improvement over placebo in treating behavioral symptoms, as assessed by the Clinical Global Impression-Improvement (CGI-I) scale.

Despite the lack of statistical benefit, the most common areas of reported improvement in both the core and extension studies included behavior, mood, engagement, and communication, suggesting potential subjective benefits that may warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. Bailey, DB., Berry-Kravis, E., Wheeler, A., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33927413/

Inhibition of phosphodiesterase-4D in adults with fragile X ... The study met the primary outcome measure since BPN14770 was well tolerated with no meaningful differences between the active and placebo treatment arms. The ...

2. shionogi.com shionogi.com/us/en/news/2024/07/shionogi-provides-updates-on-zatolmilast-an-investigational-drug-for-fragile-x-syndrome-including-recent-changes-to-study-protocol-to-increase-access-for-participants-and-families.html

Shionogi Provides Updates on Zatolmilast, an ... Shionogi today announced progress on the development program for zatolmilast (BPN14770), an investigational drug for Fragile X syndrome (FXS).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05358886

NCT05358886 | A Study of BPN14770 in Male Adults ... A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) with Fragile X Syndrome. Official Title.

4. fragilex.org fragilex.org/research/opportunities/tetra-bpn14770/

Clinical Trials: Phase 2B/3 Studies of BPN14770 in Fragile ... About the Study · Potential benefits are improvement in cognitive (language and vocabulary) function and improvement in daily activities/behavior. · Potential ...

5. nature.com nature.com/articles/s41398-025-03558-2

ROC Analysis of Biomarker Combinations in Fragile X ... Our novel identification of BPN14770 efficacy in PAF adds to previous findings of cognitive improvements with BPN214770, as peak alpha is ...

6. shionogi.com shionogi.com/us/en/innovation/fragile-x-syndrome-clinical-trials.html

Fragile X Syndrome Clinical Trials Zatolmilast is an investigational drug. Safety and efficacy have not been established. There is no guarantee that zatolmilast will be approved by any health ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05358886

A Study of BPN14770 in Male Adults (Aged 18 to 45) With ... Inclusion Criteria: Male subject aged 18 to 45 years at screening visit. Subject has FXS with a molecular genetic confirmation of the full fragile X mental ...