A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum

Pseudoxanthoma Elasticum Clinical Trial

Official title:

A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study of DS-1211b in Individuals With PseudoXanthoma Elasticum

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05569252
• Other study ID #: DS1211-A-U201
• Secondary ID: 2022-000676-19
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 20, 2022
• Est. completion date: April 2024

Study information

• Verified date: October 2023
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Pseudoxanthoma Elasticum

Intervention

Drug:
• DS-1211b
DS-1211b tablet administered once daily in the morning either in the fasted state or with a meal

Other:
• Placebo
Placebo tablet administered once daily in the morning either in the fasted state or with a meal

Locations

Country	Name	City	State
Netherlands	UMC Utrecht	Utrecht
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	Clinilabs	New York	New York
United States	Boston Neuro Research Center	North Dartmouth	Massachusetts
United States	Infinity Medical Research Inc	North Dartmouth	Massachusetts
United States	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania
United States	Frontage Clinical Services, Inc.	Secaucus	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	PXE International

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b		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
Primary	Change from Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels		Screening (Days -1 to -30) and at Days 1, 15, 43, 84, 86-88, and 98 post-dose of 12-week treatment period
Primary	Change from Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels		Screening (Days -1 to -30) and at Days 1, 15, 43, 84
Primary	Change from Baseline in Pharmacodynamic Parameter Pyridoxal 5'-phosphate (PLP) Levels		Screening (Days -1 to -30) and at Days 1, 15, 43, 84, 86-88, and 98 post-dose of 12-week treatment period
Secondary	Pharmacokinetic Parameter Maximum Concentration (Cmax)		Days, 1, 15, 43, and 84
Secondary	Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)		Days, 1, 15, 43, and 84
Secondary	Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)		Days, 1, 15, 43, and 84
Secondary	Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)		Days, 1, 15, 43, and 84