Back to resultsA Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects
Primary Purpose
Netherton Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DS-2325a
DS-2325a
Placebo
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Netherton Syndrome focused on measuring Netherton Syndrome, DS-2325a, Healthy Participants
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Worldwide Clinical Trials
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
DS-2325a SC
Placebo SC
DS-2325a IV
Placebo IV
Arm Description
Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 30 mg).
Participants who will be randomized to receive placebo as a subcutaneous (SC) injection.
Participants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg).
Participants who will be randomized to receive placebo as an intravenous infusion.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Pharmacokinetic Parameter Last Measurable Time (Tlast)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Pharmacokinetic Parameter Elimination Half-life (T1/2)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05388903
Brief Title
A Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
June 20, 2022 (Actual)
Primary Completion Date
January 26, 2023 (Actual)
Study Completion Date
January 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Netherton Syndrome
Keywords
Netherton Syndrome, DS-2325a, Healthy Participants
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DS-2325a SC
Arm Type
Experimental
Arm Description
Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 30 mg).
Arm Title
Placebo SC
Arm Type
Placebo Comparator
Arm Description
Participants who will be randomized to receive placebo as a subcutaneous (SC) injection.
Arm Title
DS-2325a IV
Arm Type
Experimental
Arm Description
Participants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg).
Arm Title
Placebo IV
Arm Type
Placebo Comparator
Arm Description
Participants who will be randomized to receive placebo as an intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
DS-2325a
Intervention Description
Subcutaneous injection (starting dose 30 mg)
Intervention Type
Drug
Intervention Name(s)
DS-2325a
Intervention Description
Intravenous infusion (starting dose 100 mg)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
Number of Participants with Any Treatment-emergent Adverse Events Following Administration of DS-2325a
Description
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.
Time Frame
Screening (Day -28 to -3) pre-dose up to Day 57 post-dose
Secondary Outcome Measure Information:
Title
Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Pharmacokinetic Parameter Last Measurable Time (Tlast)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Pharmacokinetic Parameter Elimination Half-life (T1/2)
Description
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
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
Title
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Number of Participants Who Have Treatment-emergent ADA
Description
Blood samples will be collected to determine ADAs.
Time Frame
Day 1 pre-dose and 336 hours (hr), 552 hrs, 696 hrs, and 1344 hrs post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Director
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Worldwide Clinical Trials
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Learn more about this trial
A Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects
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