Zatolmilast for Fragile X Syndrome

Not currently recruiting at 23 trial locations

Overseen By CEO

Age: < 65

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Tetra Discovery Partners

Disqualifiers: Cardiovascular, Renal, Hepatic, Psychiatric, others

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 explore the effects of a new treatment, BPN14770 (also known as zatolmilast), for male adolescents with Fragile X Syndrome (FXS). Fragile X Syndrome is a genetic condition that can cause learning and behavior challenges. The study will test how the body processes different doses of the drug and compare its effectiveness against a placebo (a harmless pill with no active ingredients). The trial seeks boys aged 9 to under 18 who have a confirmed diagnosis of FXS, are on up to three stable psychotropic medications, and can attend regular clinic visits with a caregiver. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to important advancements in FXS treatment.

Will I have to stop taking my current medications?

You can continue taking your current medications if they are stable and within the allowed types. You must be on no more than 3 prescribed psychotropic medications, and these must be at a stable dose for at least 4 weeks before the study. Anti-epileptic medications are allowed if they are for seizures and must be stable for 12 weeks before the study.

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

Research has shown that BPN14770, also known as zatolmilast, has demonstrated good safety results in various studies. For example, a recent trial found that zatolmilast was well-tolerated, with participants experiencing no major side effects. Another study noted that the treatment not only had excellent safety but also improved symptoms.

Several studies have tested the drug with participants aged 9 to 45, offering more information on its safety across different age groups. While every treatment can have some side effects, evidence so far suggests that BPN14770 is generally safe for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for fragile X syndrome?

Most treatments for Fragile X Syndrome focus on managing symptoms, but BPN14770 offers a novel approach by targeting the cognitive processes directly. This treatment is unique because it acts on the phosphodiesterase-4D (PDE4D) enzyme, which is believed to play a crucial role in memory and learning functions. Researchers are excited about BPN14770 because it has the potential to improve cognitive outcomes with fewer side effects compared to current options like behavioral therapy and medications that address only specific symptoms. By directly influencing brain signaling pathways, BPN14770 may offer a more comprehensive and effective treatment for those with Fragile X Syndrome.

What evidence suggests that this trial's treatments could be effective for fragile X syndrome?

Research has shown that BPN14770, also known as zatolmilast, could help treat Fragile X syndrome (FXS). Studies suggest it may improve thinking skills, language, and daily activities, which are often challenging for those with FXS. The drug affects brain signals. Participants in this trial will receive either BPN14770 or a placebo. Early results indicated that BPN14770 is generally safe, with no major side effects compared to a placebo. Overall, zatolmilast appears to be a promising option for enhancing the quality of life in people with FXS. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for male adolescents aged 12 to <18 with Fragile X Syndrome confirmed by genetic testing. They can be on up to three psychotropic medications (excluding anti-epileptics used for seizures), which must be stable in dose for four weeks prior. Participants should not have significant health issues, substance abuse history, or recent participation in other trials.

Inclusion Criteria

My non-drug treatments have been the same for the last 4 weeks.

Willing to practice barrier contraception if sexually active; abstinence accepted

I haven't had a seizure for 3 months, or 2 years if not taking seizure medication.

Exclusion Criteria

I do not have any major psychiatric conditions or active diseases that could interfere with my participation.

My kidney function is impaired with high creatinine levels.

I weigh less than 25 kg or my BMI is above the 97th percentile for my age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Open-label Pharmacokinetics Assessment

Open-label, single-dose pharmacokinetics assessment of BPN14770 25 mg and 50 mg

1 week

Part 2: Double-blind Treatment

Double-blind, randomized treatment with either BPN14770 or placebo

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
• Placebo
• zatolmilast

Trial Overview The study tests BPN14770's effects and how it's processed in the body compared to a placebo. Part 1 involves an open-label assessment of single doses, while Part 2 is double-blind and randomized between the drug and placebo groups.

How Is the Trial Designed?

Group I: Study Drug Active Control 1 Intervention

Subjects will receive 15 mg BID or 25mg BID dose of BPN14770

Group II: Placebo Arm Placebo Group 1 Intervention

Subjects will receive matching Placebo

Who Is Running the Clinical Trial?

Tetra Discovery Partners

Lead Sponsor

Trials

9

Recruited

1,000+

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

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 ... About the Study · Potential benefits are improvement in cognitive (language and vocabulary) function and improvement in daily activities/behavior. · Potential ...

4. 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 ...

5. 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 ...

6. 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.

7. wmed.edu wmed.edu/node/2647

Tetra Therapeutics Announces Positive Topline Results ... In this single-center, randomized, placebo-controlled, two-way crossover study, BPN14770 demonstrated excellent safety as well as benefits on ...