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

NCT05569252 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: DS1211-A-U2012022-000676-19
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 7

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.

Conditions

Pseudoxanthoma Elasticum

Keywords

Pseudoxanthoma Elasticum; DS-1211b

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b

  TEAEs are defined as events that start on or after the first dose of study drug or start prior to but then worsen after the first dose of study drug. Adverse events are coded using MedDRA version 26.1.

  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

• Percent Change From Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels

  ALP levels were assessed using the IFCC serum assay.

  Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period

• Percent Change From Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels

  PPi levels were assessed from collected plasma.

  Pre-dose on Days 15, 43, and 84 of 12-week treatment period

• Percent Change From Baseline in Pharmacodynamic Parameter Pyridoxal 5'-Phosphate (PLP) Levels

  PLP levels were assessed from collected plasma.

  Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period

Secondary Outcomes (4)

• Pharmacokinetic Parameter Maximum Concentration (Cmax)

  Day1 and Day 84 post-dose of 12-week treatment period

• Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)

  Day 1 and Day 84 post-dose of 12-week treatment period

• Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)

  Day 1 and Day 84 post-dose of 12-week treatment period

• Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)

  Day 1 and Day 84 post-dose of 12-week treatment period

Study Arms (4)

DS-1211b low dose

EXPERIMENTAL

Participants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks.

Drug: DS-1211b

DS-1211b middle dose

EXPERIMENTAL

Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.

Drug: DS-1211b

DS-1211b high dose

EXPERIMENTAL

Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.

Drug: DS-1211b

Placebo

PLACEBO COMPARATOR

Participants who will be randomized to receive a placebo tablet once daily for 12 weeks.

Other: Placebo

Interventions

DS-1211b DRUG

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

DS-1211b high dose; DS-1211b low dose; DS-1211b middle dose

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead
• PXE International: collaborator

Study Sites (7)

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Boston Neuro Research Center

North Dartmouth, Massachusetts, 02747, United States

Location

Infinity Medical Research Inc

North Dartmouth, Massachusetts, 02747, United States

Location

Frontage Clinical Services, Inc.

Secaucus, New Jersey, 07094, United States

Location

Clinilabs

New York, New York, 10019, United States

Location

Clinical Research of Philadelphia, LLC

Philadelphia, Pennsylvania, 19114, United States

Location

UMC Utrecht

Utrecht, 3584, Netherlands

Location

MeSH Terms

Conditions

Pseudoxanthoma Elasticum

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo_us@daiichisankyo.com

9089926400

Study Officials

• Clinical Director

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 6, 2022
• Study Start: October 20, 2022
• Primary Completion: November 21, 2023
• Study Completion: November 21, 2023
• Last Updated: December 31, 2024
• Results First Posted: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

US (6); NL (1)