Pseudoxanthoma ElasticumPhase 2NCT05569252

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

A Phase 2 study testing DS-1211b in people with Pseudoxanthoma Elasticum, run by Daiichi Sankyo at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Pseudoxanthoma Elasticum
What is being tested?: DS-1211b
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 65 participants
Where: 7 sitesin 2 countries
Study dates: 20 Oct 2022to 21 Nov 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Show all 16Show fewer

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

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States6 sites

Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
Clinilabs
New York, New York, 10019
Boston Neuro Research Center
North Dartmouth, Massachusetts, 02747
Infinity Medical Research Inc
North Dartmouth, Massachusetts, 02747
Clinical Research of Philadelphia, LLC
Philadelphia, Pennsylvania, 19114
Frontage Clinical Services, Inc.
Secaucus, New Jersey, 07094

Other trials in United States

Netherlands1 site

UMC Utrecht
Utrecht, 3584

Other trials in Netherlands

About this study

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

Read the 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.

Conditions: Pseudoxanthoma Elasticum
Being tested: DS-1211b, Placebo
Keywords: Pseudoxanthoma Elasticum, DS-1211b
Medical subject headings: Pseudoxanthoma Elasticum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT05569252
Study group	Role	What they receive
DS-1211b low dose	Experimental	Participants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks. Receives: Drug: DS-1211b
DS-1211b middle dose	Experimental	Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks. Receives: Drug: DS-1211b
DS-1211b high dose	Experimental	Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks. Receives: Drug: DS-1211b
Placebo	Placebo comparator	Participants who will be randomized to receive a placebo tablet once daily for 12 weeks. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Pharmacokinetic parameter Cmax was estimated using population PK modeling.
Measured: Day1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Pharmacokinetic parameter Tmax was assessed using population PK modeling.
Measured: Day 1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)
Pharmacokinetic parameter Ctrough was assessed using observed concentrations at 10 hours post-dose.
Measured: Day 1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)
Pharmacokinetic parameter AUCtau was assessed using population PK modeling.
Measured: Day 1 and Day 84 post-dose of 12-week treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Oct 202221 Nov 2023

First posted6 Oct 2022
Study start20 Oct 2022
Primary completion21 Nov 2023
Study completion21 Nov 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pseudoxanthoma ElasticumStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05569252
Sponsor's protocol ID: DS1211-A-U201
Other IDs: 2022-000676-19
Status last verified: Dec 2024
First submitted: 4 Oct 2022
Last updated: 31 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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/

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Purinergic Compounds in Pseudoxanthoma Elasticum
Pseudoxanthoma Elasticum
RecruitingObservational study
Impact of Optimized Recruitment and Follow-up of Patients With Pseudoxanthoma Elasticum (PXE)
Pseudoxanthoma Elasticum
Recruiting
CHOPXE - Analysis of Choriocapillaris Flow Deficits in Patients With Pseudoxanthoma Elasticum
Pseudoxanthoma Elasticum, Tomography, Optical Coherence
RecruitingObservational study
Progression Assessment of PXE-associated Alterations
Pseudoxanthoma Elasticum, Angioid Streaks
Active, not recruitingObservational study
Progression Rate of Pseudoxanthoma Elasticum-associated Choroidal and Retinal Degeneration
Pseudoxanthoma Elasticum

All Pseudoxanthoma Elasticum trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
ClinicalTrials.gov ID: NCT05569252
Acronym / sponsor ID: DS1211-A-U201
Conditions: Pseudoxanthoma Elasticum
Keywords: Pseudoxanthoma Elasticum, DS-1211b
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 65 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Collaborators: PXE International
Study start: 20 Oct 2022 (actual)
Primary completion: 21 Nov 2023 (actual)
Study completion: 21 Nov 2023 (actual)
First posted: 6 Oct 2022 (actual)
Results: Posted 31 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
DS-1211b low dose	Experimental	Drug: DS-1211bParticipants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks.
DS-1211b middle dose	Experimental	Drug: DS-1211bParticipants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.
DS-1211b high dose	Experimental	Drug: DS-1211bParticipants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.
Placebo	Placebo comparator	Other: PlaceboParticipants who will be randomized to receive a placebo tablet once daily for 12 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DS-1211bDS-1211b tablet administered once daily in the morning either in the fasted state or with a meal	Drug	DS-1211b high dose, DS-1211b low dose, DS-1211b middle dose
PlaceboPlacebo tablet administered once daily in the morning either in the fasted state or with a meal	Other	Placebo

Primary outcome

Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b
Time frame: 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
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.
Percent Change From Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels
Time frame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
ALP levels were assessed using the IFCC serum assay.
Percent Change From Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels
Time frame: Pre-dose on Days 15, 43, and 84 of 12-week treatment period
PPi levels were assessed from collected plasma.
Percent Change From Baseline in Pharmacodynamic Parameter Pyridoxal 5'-Phosphate (PLP) Levels
Time frame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
PLP levels were assessed from collected plasma.

4 secondary outcomes

Pharmacokinetic Parameter Maximum Concentration (Cmax)
Time frame: Day1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Time frame: Day 1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)
Time frame: Day 1 and Day 84 post-dose of 12-week treatment period
Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)
Time frame: Day 1 and Day 84 post-dose of 12-week treatment period

Results and safety

Results posted to the registry on 31 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DS-1211b Low Dose	16	15
DS-1211b Middle Dose	16	16
DS-1211b High Dose	16	16
Placebo	17	17

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

Time frame: 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. Count of participants. Unit: Participants

Measure	DS-1211b Low Dose n = 16	DS-1211b Middle Dose n = 16	DS-1211b High Dose n = 16	Placebo n = 17
Any TEAE	8	7	6	6
Any TEAE leading to death	0	0	0	0
Any TEAE by maximum severity, mild	4	6	4	3
Any TEAE by maximum severity, moderate	3	1	2	3
Any TEAE by maximum severity, severe	1	0	0	0
Any serious TEAE	1	0	0	0
Any serious TEAE leading to drug interruption	0	0	0	0
Any serious TEAE leading to drug discontinuation	0	0	0	0

Population analysed: Treatment-emergent adverse events were assessed in the Safety Analysis Set.

Primary outcome: Percent Change From Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels

Time frame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period. Mean (Standard Deviation). Unit: percent change

Measure	DS-1211b Low Dose n = 16	DS-1211b Middle Dose n = 16	DS-1211b High Dose n = 16	Placebo n = 17
Day 15	17.93 (10.60)	24.39 (14.45)	39.40 (11.52)	-0.48 (6.14)
Day 43	25.02 (17.54)	42.89 (30.26)	63.48 (35.68)	-2.54 (10.38)
Day 84	25.54 (16.89)	39.81 (20.19)	61.90 (37.86)	-4.31 (9.58)
Day 86-88	16.60 (18.39)	29.93 (14.61)	49.67 (26.00)	-3.20 (9.46)
Day 98	7.65 (15.34)	9.48 (14.99)	22.95 (22.42)	-0.05 (13.72)

Population analysed: ALP levels were assessed in participants with available data in the Biomarker Analysis Set.

Primary outcome: Percent Change From Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels

Time frame: Pre-dose on Days 15, 43, and 84 of 12-week treatment period. Mean (Standard Deviation). Unit: percent change

Measure	DS-1211b Low Dose n = 16	DS-1211b Middle Dose n = 16	DS-1211b High Dose n = 16	Placebo n = 17
Day 15	118.97 (362.42)	11.32 (50.13)	23.95 (69.94)	13.33 (61.00)
Day 43	17.75 (50.05)	-5.55 (36.74)	4.59 (19.47)	12.97 (38.33)
Day 84	23.48 (78.04)	81.77 (313.08)	24.27 (97.87)	4.28 (41.45)

Population analysed: PPi levels were assessed in participants with available data in the Biomarker Analysis Set.

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

Time frame: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period. Mean (Standard Deviation). Unit: percent change

Measure	DS-1211b Low Dose n = 16	DS-1211b Middle Dose n = 16	DS-1211b High Dose n = 16	Placebo n = 17
Day 15	11.01 (53.93)	45.42 (92.18)	50.97 (56.78)	3.42 (36.86)
Day 43	8.56 (42.26)	36.73 (79.89)	25.00 (48.51)	16.25 (35.09)
Day 84	12.03 (46.95)	53.07 (110.74)	6.04 (38.72)	-8.44 (41.44)
Day 86-88	-5.96 (27.93)	-6.52 (41.25)	-28.76 (31.72)	-10.77 (45.53)
Day 98	6.10 (47.54)	-10.96 (45.58)	-8.41 (35.10)	17.07 (98.34)

Population analysed: PLP levels were assessed using Biomarker Analysis Set.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events were collected from the time of signing the informed consent form up to 14 (±5) days after the last dose of study medication, up to 98 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DS-1211b Low Dose	1 of 16 (6.3%)	8 of 16 (50%)	0 of 16
DS-1211b Middle Dose	0 of 16 (0%)	7 of 16 (43.8%)	0 of 16
DS-1211b High Dose	0 of 16 (0%)	6 of 16 (37.5%)	0 of 16
Placebo	0 of 17 (0%)	6 of 17 (35.3%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. 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/

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Impact of Optimized Recruitment and Follow-up of Patients With Pseudoxanthoma Elasticum (PXE)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Director study director

Daiichi Sankyo

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DS-1211b in people with Pseudoxanthoma Elasticum, run by Daiichi Sankyo at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05569252.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2024.