BPN14770 for Fragile X Syndrome

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

171 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called BPN14770 in men aged 18 to 45 who have Fragile X Syndrome. The medication aims to improve brain function by balancing chemicals that help with thinking and memory.

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.

How is the drug BPN14770/zatolmilast unique for treating Fragile X Syndrome?

BPN14770/zatolmilast is unique because it targets a different mechanism in the brain compared to other treatments, potentially offering a new approach to managing Fragile X Syndrome. While other drugs like mavoglurant focus on blocking specific receptors (mGluR5), BPN14770/zatolmilast may work through different pathways, providing an alternative option for patients. ^{1 2 3 4 5}

Research Team

Elizabeth Berry-Kravis, MD, PhD

Principal Investigator

Rush Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. [2016]

2. England pubmed.ncbi.nlm.nih.gov

A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. [2019]

5. England 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. [2018]