CoA-Z in Pantothenate Kinase-associated Neurodegeneration (PKAN)

A Phase 2 Study of a Vitamin Metabolite for PKAN

The purpose of this study is to learn more about how people with the condition pantothenate kinase-associated neurodegeneration (PKAN) respond to a specialized study product. We are hoping to find out if the study product is safe, what effects-good and bad-the study product causes, and whether the study product changes certain measures of disease in PKAN.

Study Overview

• Status: Completed
• Conditions: Pantothenate Kinase-Associated Neurodegeneration
• Intervention / Treatment: Other: CoA-Z; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 89 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a diagnosis of PKAN confirmed by: a) genetic testing confirming 2 pathogenic or likely pathogenic mutations, or (b) typical findings on exam and brain MR imaging with only one pathogenic mutation +/- a second likely pathogenic or VOUS in PANK2, or (c) typical findings on exam and brain MR imaging with a single likely pathogenic or VOUS in PANK2, or (d) be a symptomatic sibling of a proband subject meeting a, b or c.
• Be between 3 months old and 89 years old.
• Be able to take study product by mouth or feeding tube.
• Be willing and able to complete study procedures / telephone visits / blood draws independently, OR have a caregiver / parent willing and able to assist with these tasks.
• Be enrolled or willing to enroll in the PKANready natural history study (eIRB 10832).
• Be resident in North America (US or Canada) for the duration of the trial.

Exclusion Criteria:

• Have had exposure to a putative PANK2 bypass therapeutic agent in the 30 days prior to screening.
• Be concurrently enrolled in another interventional clinical trial.
• Have concurrent medical or other condition expected to preclude completion of study procedures of confound the assessment of clinical and laboratory measures of safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CoA-Z dose 1; 6 months of CoA-Z at the highest assigned dose followed by 18 months of CoA-Z at dose 2	Other: CoA-Z; People with PKAN lack a chemical to process or metabolize a certain vitamin in the brain. CoA-Z is designed to bypass this metabolic defect that causes PKAN.
Experimental: CoA-Z dose 2; 6 months of CoA-Z at the medium assigned dose followed by 18 months of CoA-Z at dose 2	Other: CoA-Z; People with PKAN lack a chemical to process or metabolize a certain vitamin in the brain. CoA-Z is designed to bypass this metabolic defect that causes PKAN.
Experimental: CoA-Z dose 3; 6 months of CoA-Z at the lowest assigned dose followed by 18 months of CoA-Z at dose 2	Other: CoA-Z; People with PKAN lack a chemical to process or metabolize a certain vitamin in the brain. CoA-Z is designed to bypass this metabolic defect that causes PKAN.
Placebo Comparator: Placebo; 6 months of placebo, followed by 18 months of CoA-Z at dose 2 (medium dose)	Other: CoA-Z; People with PKAN lack a chemical to process or metabolize a certain vitamin in the brain. CoA-Z is designed to bypass this metabolic defect that causes PKAN.; Other: Placebo; The placebo is a strawberry-flavored syrup that looks and tastes like CoA-Z but has no active CoA-Z in it.
Experimental: Open-label arm; Up to 24 months of CoA-Z at dose 2	Other: CoA-Z; People with PKAN lack a chemical to process or metabolize a certain vitamin in the brain. CoA-Z is designed to bypass this metabolic defect that causes PKAN.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-emergent Adverse Events Assessed Using CTCAE v4.0	Safety will be measured using the number of treatment-emergent adverse events (both AE and SAE) by treatment arm. Counts are adjusted for number of prescription medications at baseline as a measure of baseline disease severity.	6 months following first dose in double-blind phase
Number of Treatment-emergent Clinically Significant Laboratory Abnormalities on Complete Blood Count.	Safety will be assessed by measuring the number of treatment-emergent clinically significant laboratory abnormalities on Complete Blood Count. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators.	6-month randomized, double-blind, placebo-controlled phase
Number of Treatment-emergent Clinically Significant Laboratory Abnormalities on Comprehensive Metabolic Profile.	Safety will be assessed by measuring the number of treatment-emergent clinically significant laboratory abnormalities on Comprehensive Metabolic Profile by collection month. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators.	6-month randomized, double-blind, placebo-controlled phase
Number of Participants Retained in Each Arm.	Tolerability will be assessed by measuring the number of participants retained in each arm over the course of the study.	6 month randomized, double-blind, placebo-controlled period
Mean Percent of Study Product Consumed.	Tolerability will be assessed by adherence to the study product regimen arm at each follow-up time point.	6-month randomized, double-blind, placebo-controlled phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CoASY mRNA Expression	Average relative CoASY gene expression, measured as the ratio to baseline of 1 / (2^[COASY Ct - 18s Ct]), where Ct = cycle time and 18s is a housekeeping gene. Values >1 reflect higher expression.	Up to 6 months after first dose

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Washington State University; Oregon State University; Spoonbill Foundation; Spoonbill
• Investigators: Principal Investigator: Penelope Hogarth, M.D., Oregon Health and Science University; Principal Investigator: Susan J Hayflick, MD, Oregon Health and Science University

Publications and helpful links

Helpful Links

• Trial information website

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Actual): September 1, 2024
• Study Completion (Actual): January 1, 2025

Study Registration Dates

• First Submitted: November 24, 2019
• First Submitted That Met QC Criteria: November 29, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Neurodegeneration with Brain Iron Accumulation; NBIA; PKAN
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neuroaxonal Dystrophies; Pantothenate Kinase-Associated Neurodegeneration
• Other Study ID Numbers: IRB00018782; R01HD097328 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be entered in a stand-alone repository that will allow for future sharing with other researchers. At this time we have not yet determined what IPD are to be shared.
• IPD Sharing Time Frame: Data will not be available until after September, 2024

Drug and device information, study documents

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