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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Study of a Vitamin Metabolite for PKAN

Conditions
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Pantothenate Kinase-Associated Neurodegeneration

Intervention / Treatment
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* Other: CoA-Z
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: An initial 6-month, dose-ranging, parallel-group, randomized, double-blind, placebo-controlled phase is followed by an 18-month, single-dose, open-label phase--these arms met enrollment goals. A direct-to-open-label arm of the study was opened to allow for additional enrollment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CoA-Z dose 1<br>6 months of CoA-Z at the highest assigned dose followed by 18 months of CoA-Z at dose 2 | Other: CoA-Z<br>* 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.<br>|
| Experimental: CoA-Z dose 2<br>6 months of CoA-Z at the medium assigned dose followed by 18 months of CoA-Z at dose 2 | Other: CoA-Z<br>* 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.<br>|
| Experimental: CoA-Z dose 3<br>6 months of CoA-Z at the lowest assigned dose followed by 18 months of CoA-Z at dose 2 | Other: CoA-Z<br>* 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.<br>|
| Placebo Comparator: Placebo<br>6 months of placebo, followed by 18 months of CoA-Z at dose 2 (medium dose) | Other: CoA-Z<br>* 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.<br>Other: Placebo<br>* The placebo is a strawberry-flavored syrup that looks and tastes like CoA-Z but has no active CoA-Z in it.<br>|
| Experimental: Open-label arm<br>Up to 24 months of CoA-Z at dose 2 | Other: CoA-Z<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing adverse events assessed by CTCAE v4.0 | Safety will be measured by measuring the number of participants experiencing adverse events by study period and treatment arm | 24 months | 
| Percentage of participants experiencing adverse events assessed by CTCAE v4.0 | Safety will be measured by measuring the percentage of participants experiencing adverse events by study period and treatment arm | 24 months | 
| Percentage of participants experiencing clinically significant laboratory abnormalities on Complete Blood Count. | Safety will be assessed by measuring the percentage of participants experiencing clinically significant laboratory abnormalities on Complete Blood Count by collection month. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators. | 24 months | 
| Number of participants experiencing clinically significant laboratory abnormalities on Complete Blood Count. | Safety will be assessed by measuring the number of participants experiencing clinically significant laboratory abnormalities on Complete Blood Count by collection month. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators. | 24 months | 
| Percentage of participants experiencing clinically significant laboratory abnormalities on Comprehensive Metabolic Profile. | Safety will be assessed by measuring the percentage of participants experiencing clinically significant laboratory abnormalities on Comprehensive Metabolic Profile by collection month. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators. | 24 months | 
| Number of participants experiencing clinically significant laboratory abnormalities on Comprehensive Metabolic Profile. | Safety will be assessed by measuring the number of participants experiencing clinically significant laboratory abnormalities on Comprehensive Metabolic Profile by collection month. Clinical significance will be determined by Medical Safety Monitor and Clinical Investigators. | 24 months | 
| Number of participants retained in each arm. | Tolerability will be assessed by measuring the number of participants retained in each arm at each follow up time point. | 24 months | 
| Mean percent of study product consumed. | Tolerability will be assessed by adherence to the study product regimen arm at each follow-up time point. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of CoASY mRNA expression level to that of 18s, an internal control | The pharmacodynamic profile of a putative disease biomarker will be assessed by measuring the mean level of CoASY gene expression by treatment arm across study timepoints. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurodegeneration with Brain Iron Accumulation, NBIA, PKAN