BPN14770 for Fragile X Syndrome

Not currently recruiting at 23 trial locations

Overseen By CEO

Age: < 65

Sex: Male

Trial Phase: Phase 3

Sponsor: Tetra Discovery Partners

Must be taking: Antiepileptics

Disqualifiers: Cardiovascular, Renal, Hepatic, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety of a drug called BPN14770 (also known as Zatolmilast), which may help manage symptoms of Fragile X Syndrome, a genetic condition affecting brain development. It involves participants who have already completed an initial study with this drug. The trial suits males who have finished the earlier phase without experiencing seizures or major health issues. 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 does not specify if you need to stop taking your current medications. However, if you have a seizure disorder, you must have been seizure-free during the parent study while on antiepileptic treatment.

Is there any evidence suggesting that BPN14770 is likely to be safe for humans?

Research has shown that BPN14770, also known as zatolmilast, was safe in earlier studies. Participants generally tolerated the drug well. Reports from a successful clinical trial noted zatolmilast's safety for participants. Although the drug remains under study, these findings suggest it may be well-tolerated. However, its safety and effectiveness are not fully proven, and zatolmilast is not currently approved by any health authorities. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Fragile X Syndrome?

Unlike the standard treatments for Fragile X Syndrome, which mainly focus on managing symptoms with medications like antipsychotics or ADHD drugs, BPN14770 brings something new to the table. Researchers are excited because BPN14770 targets the brain's cyclic AMP signaling, potentially improving cognitive and behavioral symptoms by modulating pathways associated with memory and learning. This unique mechanism of action sets it apart from other treatments and offers a promising new approach that could make a significant difference for patients with Fragile X Syndrome.

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

Research shows that BPN14770, also known as zatolmilast, may help treat Fragile X Syndrome (FXS). Studies have found it can improve thinking and behavior in males with FXS. The drug blocks an enzyme related to brain function, potentially aiding learning and memory. Early results suggest positive changes in caregiver and doctor ratings of symptoms. Overall, zatolmilast offers hope for better managing Fragile X Syndrome symptoms. ^{3 4 5 6 7}

Who Is on the Research Team?

Elizabeth Berry-Kravis, MD, PhD

Principal Investigator

Rush University Medical Center

Are You a Good Fit for This Trial?

This trial is for males with Fragile X Syndrome who completed a previous BPN14770 study. They must be able to consent or provide assent, use contraception if sexually active, have a caregiver, and attend regular clinic visits. Excluded are those with substance abuse, renal/hepatic impairment, significant lab/ECG abnormalities from the parent study, major psychiatric conditions (except autism or anxiety), certain diseases like AIDS or hepatitis, or participation in other trials within 30 days.

Inclusion Criteria

Subject has a parent, legal authorized guardian, or consistent caregiver

Subject has completed the Week 13 visit from one of two parent clinical trials with BPN14770: Study 204 or Study 301

Subject must be willing to practice barrier methods of contraception while on study, if sexually active

Exclusion Criteria

I have cirrhosis or unstable liver disease.

I do not have any major health issues that could affect my participation in the study.

Clinically significant abnormalities, in the investigator's judgement, in safety laboratory tests, vital signs, or ECG, as measured at the final visit of the parent study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants continue receiving BPN14770 to assess long-term safety and tolerability

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Zatolmilast/ BPN14770

Trial Overview The trial tests Zatolmilast/BPN14770 as an ongoing treatment for subjects who've finished prior studies on it. It's an open-label extension meaning everyone gets the drug and there's no placebo group; participants know what they're taking.

How Is the Trial Designed?

Group I: Study Drug (BPN14770) Experimental Treatment 1 Intervention

25mg BID Study Drug BPN14770 (Adults) or 15mg BID Study Drug BPN14770 (Adolescents with body weight \<43 kg)

Who Is Running the Clinical Trial?

Tetra Discovery Partners

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

The 2020 Special Issue on fragile X syndrome (FXS) presents nine new studies that provide updated insights into treatment options for this condition.

These manuscripts collectively contribute to the understanding of FXS and may inform future therapeutic strategies, although specific details on the findings were not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fragile X Syndrome: Recent Research Updates toward Capturing Treatments' Improvement in Clinical Trials. Budimirovic, DB., Protic, DD.[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]

Citations

1. 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 ... The studies are evaluating the safety and efficacy of zatolmilast in males aged 9 to 45 years with FXS.4-6 Tetra recently completed several ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05358886

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

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

Clinical Trials: Phase 2B/3 Studies of BPN14770 in Fragile ... Tetra Therapeutics is conducting two randomized, placebo-controlled studies of BPN14770 (zatolmilast) to learn about the drug's safety and efficacy.

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

ROC Analysis of Biomarker Combinations in Fragile X ... Fragile X Syndrome (FXS) is a rare X-linked, monogenic neurodevelopmental disorder caused by a trinucleotide repeat expansion of ≥ 200 CGG ...

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

Inhibition of phosphodiesterase-4D in adults with fragile X ... Primary outcomes were prespecified as safety and tolerability with secondary efficacy outcomes of cognitive performance, caregiver rating scales and physician ...

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

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.