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

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Netherton Syndrome

Treatments: Drug: Placebo; Drug: DS-2325a

Study type: Interventional

Funder types: Industry

Identifiers

NCT05388903

DS2325-104

Details and patient eligibility

About

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.

Full 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.

Enrollment: 64 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

---

64 participants in 4 patient groups, including a placebo group

DS-2325a SC

Experimental group

Description:

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

Treatment:

Drug: DS-2325a

Drug: DS-2325a

Placebo SC

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Placebo

DS-2325a IV

Experimental group

Description:

Participants who will be randomized to receive DS-2325a as a fixed dose intravenous (IV) infusion (starting dose 100 mg).

Treatment:

Drug: DS-2325a

Drug: DS-2325a

Placebo IV

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Placebo