Zatolmilast for PPP2R5D Syndrome

Enrolling by invitation at 2 trial locations

Overseen By Shionogi Clinical Trials Administrator Clinical Support Help Line

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Shionogi

Disqualifiers: Major psychiatric condition, 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 tests a new treatment, BPN14770 (also known as Zatolmilast), for individuals with PPP2R5D Syndrome, a condition affecting brain development and function. The trial aims to determine if the treatment is safe and well-tolerated. Participants will receive either the actual treatment or a placebo (a look-alike pill with no active ingredient) for 24 weeks. Those who complete this phase may continue in an open-label phase where everyone receives the real treatment. Individuals with PPP2R5D Syndrome, currently on no more than three psychotropic medications and with a consistent caregiver, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can be on up to 3 prescribed psychotropic medications.

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

Research has shown that BPN14770, also known as zatolmilast, has been tested for safety in people with Fragile X syndrome. These earlier studies found the treatment to be safe and effective in improving thinking skills. This suggests potential safety for other conditions, such as Jordan's syndrome.

The current study is in an early stage, indicating that the treatment has passed initial safety tests but remains under close examination. Participants in past trials did not report serious side effects, which is encouraging. However, the researchers continue to monitor safety in this study to protect all participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard options for PPP2R5D syndrome, which primarily focus on managing symptoms, BPN14770 offers a novel approach by targeting the underlying mechanisms of cognitive impairment. Researchers are excited about BPN14770 because it is designed to enhance cognitive function by inhibiting phosphodiesterase-4D (PDE4D), which plays a role in memory and learning processes. This mechanism is different from current treatments and holds promise for improving cognitive abilities in those affected by the syndrome. Additionally, BPN14770 is administered in a weight-adjusted dose twice daily, which allows for personalized treatment and potentially better outcomes.

What evidence suggests that BPN14770 might be an effective treatment for JS?

Research has shown that BPN14770, also known as Zatolmilast, holds promise for treating Jordan's Syndrome, a rare brain development disorder. In early animal studies, BPN14770 improved behavior in conditions similar to fragile X syndrome, enhancing learning and memory. The treatment increases certain brain chemicals that aid thinking and memory. Although human studies remain limited, these early results suggest potential benefits for individuals with conditions like Jordan's Syndrome. During the 24-week Double-blind Period, participants will receive either BPN14770 or a placebo, with an opportunity for all to receive BPN14770 in the Open-label Extension Period. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals aged 9 to 45 with Jordan's Syndrome (JS), a neurodevelopmental disorder. It includes those with related conditions like Klinefelter and Triple X Syndromes, but the full eligibility criteria are not provided.

Inclusion Criteria

Participant has a parent, legal authorized guardian or consistent caregiver

I have been diagnosed with PPP2R5D Neurodevelopmental Disorder.

I am currently taking 3 or fewer medications for mental health.

Exclusion Criteria

Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, or electrocardiogram (ECG), as measured during Screening

Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Participants with additional diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed

I am starting or have recently started psychotherapy or CBT.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either BPN14770 or placebo BID for 24 weeks

24 weeks

Open-label Extension

Participants receive a weight adjusted dose of BPN14770 BID for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BPN14770

Trial Overview The study tests Zatolmilast (BPN14770) against a placebo to see if it's safe and tolerable for people with JS. Participants will be randomly assigned to receive either the drug or an inactive substance.

How Is the Trial Designed?

Group I: BPN14770 Experimental Treatment 1 Intervention

Participants will receive a weight adjusted dose of BPN14770 twice daily (BID) during the 24-week Double-blind Period. Participants in the BPN14770 arm who complete the Double-blind Period will have the opportunity to continue in the Open-label Extension Period. Participants will receive a weight adjusted dose of BPN14770 BID during the 24-week Open-label Extension Period.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive BPN14770 matching placebo BID during the 24-week Double-blind Period. Participants in the placebo arm who complete the Double-blind Period will have the opportunity to continue in the Open-label Extension Period. Participants will receive a weight adjusted dose of BPN14770 BID during the 24-week Open-label Extension Period.

Who Is Running the Clinical Trial?

Shionogi

Lead Sponsor

Trials

122

Recruited

42,100+

Dr. Isao Teshirogi

Shionogi

Chief Executive Officer since 2008

PhD in Pharmaceutical Sciences from the University of Tokyo

Dr. Takuko Sawada

Shionogi

Chief Medical Officer since 2022

MD from a recognized institution (specific details not found)

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06717438

Study of Zatolmilast (BPN14770) in Participants With ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

2. neurologylive.com neurologylive.com/view/shionogi-initiates-first-ever-human-study-testing-therapy-ultra-rare-jordan-s-syndrome

Shionogi Initiates First-Ever Human Study Testing Therapy ... Zatolmilast is being tested for Jordan's syndrome, a rare neurodevelopmental disorder caused by PPP2R5D gene mutations. The phase 2 trial ...

3. shionogi.com shionogi.com/us/en/news/2025/02/shionogi-and-jordans-guardian-angels-announce-first-ever-human-drug-study-for-jordans-syndrome-an-ultra-rare-genetic-neurodevelopmental-disorder.html

Shionogi and Jordan's Guardian Angels Announce First- ... The Phase 2 randomized, double-blind, placebo-controlled study will evaluate the safety and tolerability of zatolmilast (BPN14770), an investigational ...

4. trial.medpath.com trial.medpath.com/clinical-trial/fd6a1fbaec21cdea/nct06717438-zatolmilast-bpn14770-ppp2r5d-neurodevelopmental-disorder

Study of Zatolmilast (BPN14770) in Participants ... - MedPath The primary objective of this study is to assess the safety and tolerability of BPN14770 in participants aged 9 to 45 years with JS.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11866550/

and cGMP-theory-based pharmacological therapy for fragile X ... In preclinical studies, a 2-week sub-chronic treatment with BPN14770 in Fmr1-KO mice led to improvements in several behavioral phenotypes, ...