Clinical trial NCT05388903: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Netherton Syndrome
Keywords: Netherton Syndrome
DS-2325a
Healthy Participants
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2022-05-24
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
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 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.

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.

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 57 post-dose
Secondary outcomes:
measure: Pharmacokinetic Parameter Area Under the Concentration Curve (AUC)
timeFrame: 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
measure: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
timeFrame: 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
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetic Parameter Last Measurable Time (Tlast)
timeFrame: 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
measure: Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
timeFrame: 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
measure: Pharmacokinetic Parameter Elimination Half-life (T1/2)
timeFrame: 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
measure: Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Number of Participants Who Have Treatment-emergent ADA
timeFrame: Day 1 pre-dose and 336 hours (hr), 552 hrs, 696 hrs, and 1344 hrs post-dose
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Director
role: STUDY_DIRECTOR
References: