Clinical trial NCT05583669: A Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects
Official title: A Phase 1, Subject- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Netherton Syndrome
Keywords: Netherton Syndrome
DS-2325a
Healthy Participants
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2022-10-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of multiple ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after subcutaneous (SC) injections.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants with Any Treatment-emergent Adverse Events Following Administration of DS-2325a
timeFrame: Screening (Day -28 to -3) pre-dose up to Day 78 post-dose
Secondary outcomes:
measure: Pharmacokinetic Parameter Area Under the Concentration Curve (AUCtau)
timeFrame: 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
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetic Parameter Average Concentration (Cavg)
timeFrame: 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
measure: Pharmacokinetic Parameter Drug Accumulation Ratio for AUCtau and Cmax (Rac)
timeFrame: 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
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
timeFrame: 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
measure: Pharmacokinetic Parameter Terminal Elimination Half-life (T1/2)
timeFrame: 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
measure: Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
timeFrame: 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
measure: Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
timeFrame: Day 1: pre-dose and Days 15, 22, 36, 57, and 78
Other outcomes:
Locations:
city: Miami
country: United States
facility: Quotient Sciences -Miami
state: Florida
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Director
role: STUDY_DIRECTOR
References: