Netherton SyndromePhase 1NCT05388903
A Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous 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 45 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
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2022to 26 Jan 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must give written informed consent to participation in the study prior to Screening
- Healthy men and women 18 to 45 years of age (inclusive), with a BMI of 18 kg/m2 to 30 kg/m^2 (inclusive) at Screening
- All women must have a negative serum pregnancy test at Screening and all women of childbearing potential must have a negative urine pregnancy test on Day -1
- Women must not be lactating during the study treatment period and for 3 months after the last dose of study treatment
- Women of childbearing potential must practice effective contraception during the study treatment period and for 3 months after the last dose of study treatment. They must agree to use 2 different means of nonhormonal contraceptive methods
- Women of non-childbearing potential must be either surgically sterile (ie, bilateral tubal ligation at least 3 months prior to dosing) or in menopausal state confirmed as follows: 1 year of spontaneous amenorrhea without an alternative medical cause and a serum FSH level ≥40 mIU/mL
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- Men must agree to use contraception (condom with spermicide) during the study treatment period and for at least 3 months after the last dose of study treatment or be surgically sterile (vasectomy at least 3 months prior to dosing)
- Women should not donate eggs and men should not donate sperm during the study treatment period and for at least 3 months after the last dose of study treatment
- Participants must be in good health as determined by Screening medical history, physical examination, vital signs, ECGs, serum chemistry, hematology, virology, and urinalysis performed at Screening and on Day -1
Who cannot join
- History or current chronic lung disease including asthma, chronic obstructive pulmonary disease (COPD), or heavy smoking of >10 pack years
- Previous or current treatment with systemic corticosteroids or any immunosuppressive agents
- Participants who have received a transfusion or any blood products within the last year prior to dosing
- Participants who have made any blood donation or have had a loss of blood of ≥500 mL within 56 days prior to the dose of study drug
- Participants who consume more than 21 units of alcohol per week (1 unit of alcohol equals 1/2 pint of beer, 4 ounces of wine, or 1 ounce of spirits) or those participants who have a significant history of alcoholism or drug/chemical abuse within the last 2 years.
- Participants with positive results on tests for drugs of abuse, cotinine, or alcohol at Screening and/or Day -1.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Subjects- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous 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 first-in-human study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after both subcutaneous (SC) injections and intravenous (IV) infusions, as it may have to be given intravenously to young patients and as loading dose.
- 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 30 mg)
DS-2325aDrug
Intravenous infusion (starting dose 100 mg)
PlaceboDrug
Subcutaneous injection
PlaceboDrug
Intravenous infusion
| 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 30 mg). Receives: Drug: DS-2325a |
| Placebo SC | Placebo comparator | Participants who will be randomized to receive placebo as a subcutaneous (SC) injection. Receives: Drug: Placebo |
| DS-2325a IV | Experimental | Participants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg). Receives: Drug: DS-2325a |
| Placebo IV | Placebo comparator | Participants who will be randomized to receive placebo as an intravenous infusion. 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 57 post-dose
Secondary outcomes (7)
Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Last Measurable Time (Tlast)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Elimination Half-life (T1/2)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Measured: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Number of Participants Who Have Treatment-emergent ADA
Blood samples will be collected to determine ADAs.
Measured: Day 1 pre-dose and 336 hours (hr), 552 hrs, 696 hrs, and 1344 hrs post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2022
- Study start20 Jun 2022
- Primary completion26 Jan 2023
- Study completion26 Jan 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 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
- NCT05388903
- Sponsor's protocol ID
- DS2325-104
- Status last verified
- Mar 2023
- First submitted
- 19 May 2022
- Last updated
- 6 Mar 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) 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/
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Subjects- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05388903
- Acronym / sponsor ID
- DS2325-104
- Conditions
- Netherton Syndrome
- Keywords
- Netherton Syndrome, DS-2325a, Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 20 Jun 2022 (actual)
- Primary completion
- 26 Jan 2023 (actual)
- Study completion
- 26 Jan 2023 (actual)
- First posted
- 24 May 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 first-in-human study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after both subcutaneous (SC) injections and intravenous (IV) infusions, as it may have to be given intravenously to young patients and as loading dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| 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 30 mg). |
| Placebo SC | Placebo comparator | Drug: PlaceboParticipants who will be randomized to receive placebo as a subcutaneous (SC) injection. |
| DS-2325a IV | Experimental | Drug: DS-2325aParticipants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg). |
| Placebo IV | Placebo comparator | Drug: PlaceboParticipants who will be randomized to receive placebo as an intravenous infusion. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Participants must give written informed consent to participation in the study prior to Screening
- Healthy men and women 18 to 45 years of age (inclusive), with a BMI of 18 kg/m2 to 30 kg/m^2 (inclusive) at Screening
- All women must have a negative serum pregnancy test at Screening and all women of childbearing potential must have a negative urine pregnancy test on Day -1
- Women must not be lactating during the study treatment period and for 3 months after the last dose of study treatment
- Women of childbearing potential must practice effective contraception during the study treatment period and for 3 months after the last dose of study treatment. They must agree to use 2 different means of nonhormonal contraceptive methods
Key exclusion criteria (6 listed)
- History or current chronic lung disease including asthma, chronic obstructive pulmonary disease (COPD), or heavy smoking of >10 pack years
- Previous or current treatment with systemic corticosteroids or any immunosuppressive agents
- Participants who have received a transfusion or any blood products within the last year prior to dosing
- Participants who have made any blood donation or have had a loss of blood of ≥500 mL within 56 days prior to the dose of study drug
- Participants who consume more than 21 units of alcohol per week (1 unit of alcohol equals 1/2 pint of beer, 4 ounces of wine, or 1 ounce of spirits) or those participants who have a significant history of alcoholism or drug/chemical abuse within the last 2 years.
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 30 mg) | Drug | DS-2325a SC |
| DS-2325aIntravenous infusion (starting dose 100 mg) | Drug | DS-2325a IV |
| PlaceboSubcutaneous injection | Drug | Placebo SC |
| PlaceboIntravenous infusion | Drug | Placebo IV |
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 57 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.
7 secondary outcomes
Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Last Measurable Time (Tlast)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Pharmacokinetic Parameter Elimination Half-life (T1/2)
Time frame: SC and IV cohorts: Day 1 pre-dose and 1, 2, 4, 8 hours (hr) post-dose; 24, 48, 96, 120, 144, 168, 192, 240, 288, 336, 384, 432, 480, 552, 624, 696, 768, 840, 1008, 1176, 1344 hr post-dose
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Number of Participants Who Have Treatment-emergent ADA
Time frame: Day 1 pre-dose and 336 hours (hr), 552 hrs, 696 hrs, and 1344 hrs post-dose
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 6 Mar 2023.
- 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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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 9 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 6 Mar 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. 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 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 57 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 6 Mar 2023.