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

NCT05388903 | Completed Phase 1 FDA Drug

• 1 other identifier: DS2325-104
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Netherton Syndrome

Keywords

Netherton Syndrome; DS-2325a; Healthy Participants

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)

  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)

  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)

  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)

  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)

  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

Study Arms (4)

DS-2325a SC

EXPERIMENTAL

Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 30 mg).

Drug: DS-2325a

Placebo SC

PLACEBO COMPARATOR

Participants who will be randomized to receive placebo as a subcutaneous (SC) injection.

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).

Drug: DS-2325a

Placebo IV

PLACEBO COMPARATOR

Participants who will be randomized to receive placebo as an intravenous infusion.

Drug: Placebo

Interventions

DS-2325a DRUG

Subcutaneous injection (starting dose 30 mg)

DS-2325a SC

Placebo DRUG

Subcutaneous injection

Placebo SC

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Netherton Syndrome

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Director

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 24, 2022
• Study Start: June 20, 2022
• Primary Completion: January 26, 2023
• Study Completion: January 26, 2023
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

US (1)