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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pseudoxanthoma Elasticum
• Intervention / Treatment: Drug: DS-1211b; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584
    • UMC Utrecht
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research Inc
    • North Dartmouth, Massachusetts, United States, 02747
      • Boston Neuro Research Center
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services, Inc.
  • New York
    • New York, New York, United States, 10019
      • Clinilabs
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Of Philadelphia, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-1211b low dose; Participants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks.	Drug: DS-1211b; DS-1211b tablet administered once daily in the morning either in the fasted state or with a meal
Experimental: DS-1211b middle dose; Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.	Drug: DS-1211b; DS-1211b tablet administered once daily in the morning either in the fasted state or with a meal
Experimental: DS-1211b high dose; Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.	Drug: DS-1211b; DS-1211b tablet administered once daily in the morning either in the fasted state or with a meal
Placebo Comparator: Placebo; Participants who will be randomized to receive a placebo tablet once daily for 12 weeks.	Other: Placebo; Placebo tablet administered once daily in the morning either in the fasted state or with a meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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
Change from Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels	Screening (Days -1 to -30) and at Days 1, 15, 43, 84
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 Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Parameter Maximum Concentration (Cmax)	Days, 1, 15, 43, and 84
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)	Days, 1, 15, 43, and 84
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)	Days, 1, 15, 43, and 84
Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)	Days, 1, 15, 43, and 84

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: PXE International
• Investigators: Study Director: Clinical Director, Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pseudoxanthoma Elasticum; DS-1211b
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Pseudoxanthoma Elasticum
• Other Study ID Numbers: DS1211-A-U201; 2022-000676-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No