Objective: To describe the methodology and novel primary efficacy outcome measure in the ongoing pivotal FORT trial in patients with pantothenate kinase-associated neurodegeneration (PKAN).

Background: PKAN is a rare autosomal recessive, progressive neurodegenerative genetic disorder caused by mutations in the PANK2 gene. Defective pantothenate metabolism results in mixed motor and cognitive symptoms. Currently there are no approved disease-modifying therapies for PKAN. Widely accepted scales for patient-reported outcomes in PKAN are also lacking. This trial examines fosmetpantotenate, a replacement therapy that crosses the blood-brain barrier to deliver phosphopantothenate to neurons and increase intracellular coenzyme A availability.

Methods: FORT is an ongoing Phase 3, randomized, double-blind, placebo-controlled pivotal trial of the efficacy and safety of fosmetpantotenate in adult and pediatric patients with PKAN (NCT03041116). Eligible patients have confirmed mutations in the PANK2 gene, are age 6 to 65 years old, with a PKAN Activities of Daily Living (PKAN-ADL) score of ≥6. Following the 24-week double-blind period, patients are eligible to receive fosmetpantotenate for up to 96-weeks in the open-label period. The PKAN-ADL scale was developed as the primary efficacy outcome as a novel, validated clinical outcomes assessment of PKAN-specific patient functioning based on patient or caregiver self-report.

Results: Enrollment of 82 patients is planned. The novel primary efficacy outcome of change in PKAN-ADL score over the 24-week double-blind period will evaluate patient improvements in PKAN-specific activities of daily living. Change in Part III of the Unified Parkinson’s Disease Rating Scale score is the secondary efficacy endpoint. Dystonia, quality of life, functional independence, ambulation, speech, and safety are also examined.

Conclusions: The FORT trial will examine fosmetpantotenate as a potential disease-modifying therapy for adult and pediatric patients with PKAN through report of patient PKAN-specific everyday function on the PKAN-ADL scale. The PKAN-ADL scale is a novel and validated patient-reported clinical outcomes measure that may indicate clinically meaningful change in clinical trials of therapeutics. The PKAN-ADL scale may be employed in clinical trials to address unmet therapeutic need in PKAN.

References: 1. Marshall RD, et al. Development of a clinical outcomes assessment (COA) in pantothenate kinase-associated neurodegeneration (PKAN): item generation and clinimetric properties [abstract 1295]. Poster presented at the International Congress of Parkinson’s Disease and Movement Disorders, June 4-8, 2017, Vancouver, Canada.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-fosmetpantotenate-replacement-therapy-fort-pivotal-trial-utilization-of-a-novel-primary-efficacy-outcome-in-patients-with-pantothenate-kinase-associated-neurodegeneration/