Study of Zatolmilast (BPN14770) in Participants With PPP2R5D Neurodevelopmental Disorder (Jordan's Syndrome [JS])

A Phase 2 Randomized, Double-blind, Placebo-controlled, Study of Zatolmilast (BPN14770) in Subjects With PPP2R5D Neurodevelopmental Disorder (Jordan's Syndrome)

The primary objective of this study is to assess the efficacy, safety, and tolerability of BPN14770 in participants aged 9 to 45 years with JS.

Study Overview

• Status: Active, not recruiting
• Conditions: Jordan's Syndrome; PPP2R5D Neurodevelopmental Disorder
• Intervention / Treatment: Drug: Placebo; Drug: BPN14770

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant is aged 9 to 45 years, inclusive.
2. Participant has confirmed/documented history of PPP2R5D Neurodevelopmental Disorder.
3. Current treatment with no more than 3 prescribed psychotropic medications.
4. Participant has a parent, legal authorized guardian or consistent caregiver.

Exclusion Criteria:

1. Participant has body weight less than 25 kilograms (kg).
2. Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, or electrocardiogram (ECG), as measured during Screening.
3. 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.
4. Participant is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPN14770; Participants will receive a weight adjusted dose of BPN14770 twice daily (BID) during the 24-week double-blind period. Participants who complete the double-blind period will have the opportunity to continue in the open-label extension (OLE) period. Participants will receive a weight adjusted dose of BPN14770 BID during the 24-week OLE period. Eligible participants who complete the double-blind period and OLE period may be offered the opportunity to participate in a 48-week extended open-label extension (Ext OLE) period. Adult participants (≥18 years of age at the start of Ext OLE) will receive an age-adjusted dose of BPN14770 BID during the Ext OLE period, while participants younger than 18 years at the start of Ext OLE will receive a weight-adjusted dose of BPN14770 BID.	Drug: BPN14770; Capsules for oral administration; Other Names: Zatolmilast
Placebo Comparator: Placebo; Participants will receive BPN14770-matching placebo BID during the 24-week double-blind period. Participants who complete the double-blind period will have the opportunity to continue in the OLE period. Participants will receive a weight adjusted dose of BPN14770 BID during the 24-week OLE period. Eligible participants who complete the double-blind period and OLE period may be offered the opportunity to participate in a 48-week Ext OLE period. Adult participants (≥18 years of age at the start of Ext OLE) will receive an age-adjusted dose of BPN14770 BID during the Ext OLE period, while participants younger than 18 years at the start of Ext OLE will receive a weight-adjusted dose of BPN14770 BID.	Drug: Placebo; Capsules for oral administration; Drug: BPN14770; Capsules for oral administration; Other Names: Zatolmilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline at Week 24 in Numerical Rating Scale Within the Domain of Language/Communication	Baseline, Week 24
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Week 96
Discontinuation-emergent Signs and Symptoms (DESS) Questionnaire Score	Week 98
Number of Participants with Seizures	Up to Week 96
Number of Participants at Suicidality Risk	Up to Week 96

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Jordan's Syndrome; JS; PPP2R5D Neurodevelopmental Disorder; Zatolmilast; BPN14770
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Syndrome; Neurodevelopmental Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; BPN14770
• Other Study ID Numbers: BPN14770-CNS-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No