What is the mechanism of action of this treatment?

Common treatments for Fragile X Syndrome (FXS) often target the underlying molecular abnormalities associated with the disorder. BPN14770, a Phosphodiesterase-4D (PDE4D) inhibitor, works by increasing the levels of cyclic AMP (cAMP) in the brain, which can help improve cognitive function and reduce behavioral symptoms. This is significant for FXS patients because the disorder is characterized by deficits in synaptic plasticity and cognitive function, which are linked to disrupted cAMP signaling pathways. By enhancing cAMP signaling, PDE4D inhibitors like BPN14770 aim to restore normal synaptic function and improve the quality of life for individuals with FXS.

What side effects are associated with this type of intervention?

Phosphodiesterase-4D inhibitors, like BPN14770, are being studied for their potential benefits in treating Fragile X Syndrome. Common side effects of this class of drugs can include gastrointestinal issues such as nausea and diarrhea, as well as headaches and dizziness. Other treatments for Fragile X Syndrome, such as stimulants, antipsychotics, and SSRIs, may cause side effects like insomnia, weight gain, fatigue, and increased anxiety. It is important to discuss these potential side effects with a healthcare provider to tailor the treatment plan to the individual's needs.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Fragile X Syndrome. However, various drugs have been studied for their potential benefits, including those targeting the underlying molecular mechanisms. BPN14770, a Phosphodiesterase-4D inhibitor, is currently under investigation for its potential to improve cognitive function in individuals with Fragile X Syndrome. Other treatments that have been explored include mGluR5 antagonists, GABA agonists, and drugs targeting the endocannabinoid system, but none have received FDA approval specifically for Fragile X Syndrome.

What other types of research exist?

Promising novel alternatives to BPN14770 for Fragile X Syndrome patients include: 1) Metformin, which has shown potential in improving cognitive function and reducing behavioral issues in FXS patients. 2) Ganaxolone, a neurosteroid that modulates GABA receptors and has demonstrated efficacy in reducing anxiety and improving behavior in FXS. 3) Lovastatin, which has been studied for its ability to reduce excessive protein synthesis linked to FXS symptoms. These alternatives are currently being explored in clinical trials and may offer new therapeutic options for FXS patients in 2024.

← Back to Search

Phosphodiesterase-4D (PDE4D) Inhibitor

BPN14770 for Fragile X Syndrome

Phase 3

Recruiting

Led By Elizabeth Berry-Kravis, MD

Research Sponsored by Tetra Discovery Partners

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1) mutation (≥200 CGG repetitions)

Male subject aged 18 to 45 years at screening visit

Must not have

Subject has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis

Subject has a body mass index of less than 18 kg/m2 or greater than 36 kg/m2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 13 weeks

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, participants will be monitored for any adverse reactions to BPN14770 compared to those taking the placebo. Side effects may include typical drug responses such as digestive issues, headaches, dizziness or allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have Fragile X Syndrome confirmed by a genetic test.

Select...

I am a man aged between 18 and 45.

Select...

I have been seizure-free for 3 months on medication or 2 years without medication.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Select...

My BMI is either below 18 or above 36.

Select...

My kidney function is impaired with high creatinine levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 13 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~13 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 13 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC)

Secondary study objectives

Aberrant Behavior Checklist (ABC) scores

Anxiety, Depression, and Mood Scale (ADAMS) scores

Caregiver Global Impression of Improvement (CaGI-I)

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: Study DrugActive Control1 Intervention

25mg BID BPN14770

Group II: PlaceboPlacebo Group1 Intervention

Placebo

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Fragile X Syndrome (FXS) often target the underlying molecular abnormalities associated with the disorder. BPN14770, a Phosphodiesterase-4D (PDE4D) inhibitor, works by increasing the levels of cyclic AMP (cAMP) in the brain, which can help improve cognitive function and reduce behavioral symptoms. This is significant for FXS patients because the disorder is characterized by deficits in synaptic plasticity and cognitive function, which are linked to disrupted cAMP signaling pathways. By enhancing cAMP signaling, PDE4D inhibitors like BPN14770 aim to restore normal synaptic function and improve the quality of life for individuals with FXS.

Clinical effects of fenfluramine on children with autism: a review of the research.Commentary: Identifying individualized predictions of response in ADHD pharmacotherapy - a commentary on Rodrigues et al. (2020).[Psychopharmacology of autistic disorders].