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

NCT05583669 | Completed Phase 1 FDA Drug

• 1 other identifier: DS2325-106
• Study Type: interventional
• Target: 24
• 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 78 post-dose

Secondary Outcomes (8)

• Pharmacokinetic Parameter Area Under the Concentration Curve (AUCtau)

  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)

  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)

  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)

  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)

  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

Study Arms (2)

DS-2325a SC

EXPERIMENTAL

Participants who will be randomized to receive DS-2325a as a fixed dose subcutaneous (SC) injection (starting dose 300 mg).

Drug: DS-2325a

Placebo SC

EXPERIMENTAL

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

Drug: Placebo

Interventions

DS-2325a DRUG

Subcutaneous injection (starting dose 300 mg)

DS-2325a SC

Placebo DRUG

Subcutaneous injection

Placebo SC

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Quotient Sciences -Miami

Miami, Florida, 33126, 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 18, 2022
• Study Start: November 8, 2022
• Primary Completion: May 11, 2023
• Study Completion: May 11, 2023
• Last Updated: May 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Studies 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 from 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)