Clinical trial NCT05569252: A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
Official title: A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pseudoxanthoma Elasticum
Keywords: Pseudoxanthoma Elasticum
DS-1211b
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: PXE International
First posted: 2022-10-06
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to evaluate the safety, tolerability, pharmacodynamics (PD) of DS-1211b, and pharmacokinetics (PK) in individuals with Pseudoxanthoma elasticum (PXE). PXE is a rare disease that is associated with significant risks of visual impairments and comorbidity from peripheral and cardiovascular diseases, and adversely impacts the quality of life in afflicted individuals.

Detailed description: DS-1211b, a potent small-molecule inhibitor of tissue-nonspecific alkaline phosphatase, is being developed for the treatment ectopic calcification diseases such as PXE. This study will assess DS-1211b (low-, middle-, and high-dose tablets) administered once daily for 12 weeks in individuals with PXE.

Eligibility criteria: Key Inclusion Criteria:

* Signed and dated informed consent
* Male or female participants aged 18 to 75 years at screening
* Have an established diagnosis of PXE
* Fully vaccinated for coronavirus disease 2019 (COVID-19) per current Center for Disease Control and Prevention guidelines

Key Exclusion Criteria:

* Have a history of bone fracture in the past 6 months
* Have a history of active metabolic bone disease, excluding osteopenia or osteoporosis without fragility fracture
* Have a history of calcium pyrophosphate deposit disease
* Have a history of hypophosphatasia
* Have a history of untreated hyperparathyroidism
* Participated in another interventional research study in the past 60 days.
* Used bisphosphonate in the preceding 12 months or had plans to use bisphosphonate during the study.
* Received Vitamin B6 supplementation \>5 mg/day in the month prior to screening and during the study
* Initiated or changed dose of Vitamin D in the preceding month prior to screening
* Have an alkaline phosphatase \<lower limit of normal (LLN) range
* Have a QTcF interval duration \>450 ms at screening
* Have moderate to severe renal insufficiency
* Are pregnant or breast-feeding women
* Are female participants unwilling to use contraceptive methods
* Have any elective surgery planned during the study period
* Have any other significant condition (medical, psychiatric, social, or medication) that, in the judgment of the Investigator, would prevent full participation or would be inappropriate for the study

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b
timeFrame: From the date of signing informed consent form up to Day 98 (14 days after last dose of study drug) post-dose of 12-week treatment period
measure: Percent Change From Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels
timeFrame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
measure: Percent Change From Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels
timeFrame: Pre-dose on Days 15, 43, and 84 of 12-week treatment period
measure: Percent Change From Baseline in Pharmacodynamic Parameter Pyridoxal 5'-Phosphate (PLP) Levels
timeFrame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
Secondary outcomes:
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax)
timeFrame: Day1 and Day 84 post-dose of 12-week treatment period
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
timeFrame: Day 1 and Day 84 post-dose of 12-week treatment period
measure: Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)
timeFrame: Day 1 and Day 84 post-dose of 12-week treatment period
measure: Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: Day 1 and Day 84 post-dose of 12-week treatment period
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: North Dartmouth
country: United States
facility: Boston Neuro Research Center
state: Massachusetts
city: North Dartmouth
country: United States
facility: Infinity Medical Research Inc
state: Massachusetts
city: Secaucus
country: United States
facility: Frontage Clinical Services, Inc.
state: New Jersey
city: New York
country: United States
facility: Clinilabs
state: New York
city: Philadelphia
country: United States
facility: Clinical Research of Philadelphia, LLC
state: Pennsylvania
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Director
role: STUDY_DIRECTOR
References: