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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Pseudoxanthoma Elasticum

Intervention / Treatment
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* Drug: DS-1211b
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudoxanthoma Elasticum, DS-1211b