A Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Netherton Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: DS-2325a; Drug: DS-2325a; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-2325a SC; Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 30 mg).	Drug: DS-2325a; Subcutaneous injection (starting dose 30 mg); Drug: DS-2325a; Intravenous infusion (starting dose 100 mg)
Placebo Comparator: Placebo SC; Participants who will be randomized to receive placebo as a subcutaneous (SC) injection.	Drug: Placebo; Intravenous infusion; Drug: Placebo; Subcutaneous injection
Experimental: DS-2325a IV; Participants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg).	Drug: DS-2325a; Subcutaneous injection (starting dose 30 mg); Drug: DS-2325a; Intravenous infusion (starting dose 100 mg)
Placebo Comparator: Placebo IV; Participants who will be randomized to receive placebo as an intravenous infusion.	Drug: Placebo; Intravenous infusion; Drug: Placebo; Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Screening (Day -28 to -3) pre-dose up to Day 57 post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)	Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.	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.	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.	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.	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.	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.	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.	Day 1 pre-dose and 336 hours (hr), 552 hrs, 696 hrs, and 1344 hrs post-dose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Actual): January 26, 2023
• Study Completion (Actual): January 26, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Healthy Participants; Netherton Syndrome; DS-2325a
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Abnormalities, Multiple; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Netherton Syndrome
• Other Study ID Numbers: DS2325-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No