Netherton SyndromePhase 1NCT05583669
A Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects
A Phase 1 study testing DS-2325a in people with Netherton Syndrome, run by Daiichi Sankyo at 1 site in United States.
Trial summary
Netherton syndrome (NS) is a rare autosomal recessive disease and no systemic treatment or standard of care currently exists for patients with NS. DS-2325a, a specific and potent inhibitor of kallikrein 5, is expected to treat NS by replacing a defective gene. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Netherton Syndrome
- What is being tested?
- DS-2325a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2022to 11 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
- Must be willing and able to comply with all study requirements.
- Healthy males or non-pregnant, non-lactating healthy females.
- Aged 18 to 50 years of age (inclusive) at the time of signing informed consent.
- BMI of 18.0 kg/m^2 to 30.0 kg/m^2 (inclusive) as measured at Screening.
- Women of childbearing potential who are sexually active with a male partner must practice effective contraception during the study treatment period and for 90 days after last IMP administration. They must agree to use 2 different means of nonhormonal contraceptive methods.
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- Women of non-childbearing potential must be either surgically sterile or in menopausal state confirmed as follows: 1 year of spontaneous amenorrhea without an alternative medical cause and a serum follicle stimulating hormone (FSH) level ≥40 mIU/mL.
- Male participants who are sexually active with a female partner of childbearing potential must use, with their partner, a condom plus an approved method of highly effective contraception from the time of informed consent until 90 days after last IMP administration.
- Women should not donate eggs and men should not donate sperm during the study treatment period and for at least 90 days after last IMP administration.
- All female participants must have a negative serum pregnancy test at Screening and Admission (Day -2).
Who cannot join
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, metabolic, endocrine, immunologic, infectious, dermatologic, neurologic, oncologic, psychological, psychiatric, ophthalmologic, or gastrointestinal disease (except cholecystectomy), as judged by the Investigator.
- History or presence of chronic lung or respiratory disease, including clinically significant asthma (as judged by the Investigator) and chronic obstructive pulmonary disease (COPD).
- History, or presence in the average of triplicate ECGs at Screening and Admission (Day -2).
- Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range, if considered clinically significant by the Investigator at Screening or Admission (Day -2).
- Creatinine clearance (CrCl) <80 mL/mina t Screening.
- History or presence of any other clinically significant condition, including laboratory abnormality, that in the opinion of the Investigator, would jeopardize the safety of the participant, obtaining informed consent, compliance to the study procedures, or the validity of the study results.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Subject- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects
Netherton syndrome (NS) is a rare autosomal recessive disease and no systemic treatment or standard of care currently exists for patients with NS. DS-2325a, a specific and potent inhibitor of kallikrein 5, is expected to treat NS by replacing a defective gene.
Read the detailed description
This study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of multiple ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after subcutaneous (SC) injections.
- Conditions
- Netherton Syndrome
- Being tested
- DS-2325a, Placebo
- Keywords
- Netherton Syndrome, DS-2325a, Healthy Participants
- Medical subject headings
- Netherton Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-2325aDrug
Subcutaneous injection (starting dose 300 mg)
PlaceboDrug
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| DS-2325a SC | Experimental | Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 300 mg). Receives: Drug: DS-2325a |
| Placebo SC | Experimental | Participants who will be randomized to receive placebo as a subcutaneous (SC) injection. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Any Treatment-emergent Adverse Events Following Administration of DS-2325a
Treatment-emergent adverse events (TEAEs) are defined as new adverse events (AEs) that occur after the dose of study drug or as AEs that were present prior to the dose of study drug but which worsened in severity after the start of study drug.
Measured: Screening (Day -28 to -3) pre-dose up to Day 78 post-dose
Secondary outcomes (8)
Pharmacokinetic Parameter Area Under the Concentration Curve (AUCtau)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Average Concentration (Cavg)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Drug Accumulation Ratio for AUCtau and Cmax (Rac)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Terminal Elimination Half-life (T1/2)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Blood samples will be collected to determine ADAs.
Measured: Day 1: pre-dose and Days 15, 22, 36, 57, and 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start8 Nov 2022
- Primary completion11 May 2023
- Study completion11 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Netherton SyndromeStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Director, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05583669
- Sponsor's protocol ID
- DS2325-106
- Status last verified
- May 2023
- First submitted
- 13 Oct 2022
- Last updated
- 18 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) 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/
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Subject- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05583669
- Acronym / sponsor ID
- DS2325-106
- Conditions
- Netherton Syndrome
- Keywords
- Netherton Syndrome, DS-2325a, Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2022 (actual)
- Primary completion
- 11 May 2023 (actual)
- Study completion
- 11 May 2023 (actual)
- First posted
- 18 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Netherton syndrome (NS) is a rare autosomal recessive disease and no systemic treatment or standard of care currently exists for patients with NS. DS-2325a, a specific and potent inhibitor of kallikrein 5, is expected to treat NS by replacing a defective gene.
Detailed description
This study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of multiple ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after subcutaneous (SC) injections.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DS-2325a SC | Experimental | Drug: DS-2325aParticipants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 300 mg). |
| Placebo SC | Experimental | Drug: PlaceboParticipants who will be randomized to receive placebo as a subcutaneous (SC) injection. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
- Must be willing and able to comply with all study requirements.
- Healthy males or non-pregnant, non-lactating healthy females.
- Aged 18 to 50 years of age (inclusive) at the time of signing informed consent.
- BMI of 18.0 kg/m^2 to 30.0 kg/m^2 (inclusive) as measured at Screening.
Key exclusion criteria (6 listed)
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, metabolic, endocrine, immunologic, infectious, dermatologic, neurologic, oncologic, psychological, psychiatric, ophthalmologic, or gastrointestinal disease (except cholecystectomy), as judged by the Investigator.
- History or presence of chronic lung or respiratory disease, including clinically significant asthma (as judged by the Investigator) and chronic obstructive pulmonary disease (COPD).
- History, or presence in the average of triplicate ECGs at Screening and Admission (Day -2).
- Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range, if considered clinically significant by the Investigator at Screening or Admission (Day -2).
- Creatinine clearance (CrCl) <80 mL/mina t Screening.
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-2325aSubcutaneous injection (starting dose 300 mg) | Drug | DS-2325a SC |
| PlaceboSubcutaneous injection | Drug | Placebo SC |
Primary outcome
Number of Participants with Any Treatment-emergent Adverse Events Following Administration of DS-2325a
Time frame: Screening (Day -28 to -3) pre-dose up to Day 78 post-dose
Treatment-emergent adverse events (TEAEs) are defined as new adverse events (AEs) that occur after the dose of study drug or as AEs that were present prior to the dose of study drug but which worsened in severity after the start of study drug.
8 secondary outcomes
Pharmacokinetic Parameter Area Under the Concentration Curve (AUCtau)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Average Concentration (Cavg)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Drug Accumulation Ratio for AUCtau and Cmax (Rac)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Terminal Elimination Half-life (T1/2)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Time frame: Day 1: pre-dose and Days 15, 22, 36, 57, and 78
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2023.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) 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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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DS-2325a in people with Netherton Syndrome, run by Daiichi Sankyo at 1 site in United States.
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 10 inclusion and 6 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 18 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Any Treatment-emergent Adverse Events Following Administration of DS-2325a (time frame: Screening (Day -28 to -3) pre-dose up to Day 78 post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2023.