Oral Pyridoxal 5'-Phosphate for the Treatment of Patients With PNPO Deficiency (MEND-PNPO)

Study of Pyridoxal 5'-Phosphate for the Treatment of Patients With PNPO Deficiency

The proposed clinical study is intended to evaluate oral P5P for the treatment of patients confirmed to have Pyridox(am)ine 5'-Phosphate Oxidase (PNPO) deficiency via genetic analysis. There is an unmet clinical need for pharmaceutical grade P5P, as to date none has been made commercially available. Patients will receive pharmaceutical grade P5P according to their normal oral P5P dosing regimen, as previously established by their physicians.

Study Overview

• Status: Recruiting
• Conditions: Pyridox(am)Ine 5'-Phosphate Oxidase Deficiency
• Intervention / Treatment: Drug: Pyridoxal Phosphate

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Laura Cole, Ph.D.; Phone Number: 204-487-7412; Email: lcole@medicure.com

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia
      • Active, not recruiting
      • Queensland Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Children's Hospital of Alabama
      • Contact: Mackenzie Keith; Phone Number: 205-934-8365; Email: mkeith@uabmc.edu
      • Principal Investigator: Monisha Goyal, MD
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital
      • Contact: Rayann Solidum; Phone Number: 415-424-1237; Email: rsolidum@stanford.edu
      • Principal Investigator: Courtney Wusthoff, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Nathan Holly; Phone Number: 720-777-5410; Email: Nathan.Holly@childrenscolorado.org
      • Principal Investigator: Johan Van Hove, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Principal Investigator: Phillip Pearl, MD
      • Contact: Melissa DiBacco, MD; Phone Number: 44617 617-919-4617; Email: Melissa.DiBacco@childrens.harvard.edu
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Active, not recruiting
      • Duke Children's Hospital
  • Ohio
    • Akron, Ohio, United States, 44308
      • Recruiting
      • Akron's Children's Hospital
      • Contact: Hilary Tonni; Phone Number: 330-543-4734; Email: htonni@akronchildrens.org
      • Principal Investigator: Matthew Ginsberg, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with confirmed PNPO deficiency via genetic analysis, whose seizures are typically controlled on P5P (oral) therapy.

   a. Typically controlled is defined as receiving multiple doses of P5P daily to control seizures. Receiving P5P for a minimum of 30 days.

2. Male and/or female patients.
3. Aged ≥2 years

(3) Patients with previous failed treatment on pyridoxine are eligible for the study (patient should be off pyridoxine for at least 24 hours).

(4) Written informed consent (by parent or guardian if under the age of 18).

Exclusion Criteria:

1. The patient has any condition or abnormality which may, in the opinion of the Investigator, compromise the safety of the patient, or influence their ability to comply with study procedures.
2. Known or suspected allergy to the trial drug or the relevant drugs given in the trial.
3. Involvement in a clinical research study within 4 weeks prior to screening and/or prior enrollment in the study. Participation in observational registry studies is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm Active; Pyridoxal 5'-Phosphate	Drug: Pyridoxal Phosphate; Oral tablets 50 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival time (time to death), including incidence of death at 12 months	The study group will be compared to a historical control group (without active treatment) for overall survival by using the method of survival analysis	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of seizures (including but not limited to status epilepticus)	The frequency of seize will be compared between different treatment periods of the current single arm: Pharmaceutical grade oral P5P treatment period vs period prior to any P5P treatment (if data available)	up to 12 months

Collaborators and Investigators

• Sponsor: Medicure

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 8, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Enzymes and Coenzymes; Coenzymes; Picolines; Pyridoxal; Vitamin B 6; Pyridoxal Phosphate
• Other Study ID Numbers: MEND-PNPO 16002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No