a study to assess the safety and pharmacokinetics of single ascending subcutaneous and intravenous doses of ds-2325a in healthy subjects

Conditions: Netherton Syndrome

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.

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.

Keywords: netherton syndrome ds-2325a healthy participants