A First-in-Human Study of KINE-101 in Healthy Volunteers

Kine Sciences Co., Ltd.

Status and phase

Completed

Phase 1

Conditions

Healthy Volunteers

Treatments

Drug: Placebo

Drug: KINE-101

Study type

Interventional

Funder types

Industry

Identifiers

NCT07343323

RA101-CR3-001

Details and patient eligibility

About

This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study that evaluates the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenous (IV) and subcutaneous (SC) formulations of KINE-101 in healthy volunteers at a single study center. Five cohorts of eight subjects each (six receiving KINE-101 and two receiving placebo) are admitted on Day -1, receive a single dose of investigational medicinal product (IMP) on Day 1, and remain in-house until Day 3, followed by outpatient visits on Days 7, 14, 28, and 42. Sentinel dosing applies in the first sub-cohort of each cohort: two sentinel subjects are dosed at least 10 minutes apart, and if no safety concerns arise during the 48-hour post-dose evaluation period, the remaining subjects in the cohort are subsequently dosed. Dosing in the second sub-cohort also occurs at intervals of at least 10 minutes. Four cohorts receive the IV formulation, with doses escalating from 10 mg up to an anticipated maximum of 300 mg. To compare relative bioavailability and characterize PK after subcutaneous administration, one SC cohort receives a single 96.8 mg dose. The number of cohorts and dose progression depend on emerging safety and PK data. Decisions to escalate, repeat, or modify dose levels are made by the Safety Review Committee (SRC), and additional cohorts may be added if deemed necessary.

Enrollment

40 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Signed IRB-approved informed consent before any screening procedures.
Healthy subjects with no clinically significant illness or disease based on medical history, physical exam, ECG, and lab tests.
Males and females aged 18-55 years at screening.
Nonsmokers or no nicotine use for ≥1 year; urine cotinine <200 ng/mL at screening and admission.
BMI 18.5-30.0 kg/m² and body weight ≥50 kg at screening.
Suitable veins for venipuncture/cannulation.
Able to fast overnight (≥10 hours).
Male subjects agree to use condoms during intercourse and for 1 month after last IMP dose.
Male subjects must not donate sperm from dosing day until 1 month after last IMP dose.
Female subjects must be of non-childbearing potential (postmenopausal ≥12 months with FSH >40 IU/L or surgical sterilization such as hysterectomy, tubal ligation, bilateral oophorectomy/salpingectomy).

Exclusion criteria

Received an investigational medicinal product (IMP) within 30 days or 5× half-life before first IMP administration.
History of alcohol abuse within 2 years, weekly intake >21 units, or positive alcohol test at screening/admission.
Current smokers or nicotine use within 12 months; positive urine cotinine at screening/admission.
Clinically significant abnormal labs: ALT, AST, or total bilirubin >ULN (or >1.5×ULN if Gilbert's), serum creatinine >ULN, eGFR <80 mL/min/1.73 m², abnormal TSH, or other clinically relevant abnormal values.
Positive drug abuse test at screening or admission.
Positive HBsAg, anti-HCV, or HIV antibody at screening.
Clinically significant psychiatric, cardiovascular, renal, hepatic, or chronic respiratory disease, including arrhythmia.
Supine BP <90 or >140 mmHg systolic, or <50 or >90 mmHg diastolic after 5 minutes supine.
Supine pulse <50 bpm or >100 bpm after 5 minutes supine.
Personal or family history of long QTc syndrome, sudden cardiac death, or hERG mutation.
Severe adverse reaction or hypersensitivity to any drug or excipients.
Blood donation or loss >400 mL within 3 months or hemoglobin below normal limits.
Use of prohibited medications, OTC drugs, herbal remedies, or supplements within 28 days before IMP administration.
Received live or attenuated vaccines or systemic corticosteroids within 3 months prior to first IMP dose.
Conditions interfering with drug absorption, distribution, metabolism, or excretion.
Employees of sponsor/CRO or close relatives involved in the study.
Unable to communicate meaningfully with study staff.
QTcF >450 ms at screening or admission.
Significant liver impairment or abnormal conjugated/direct bilirubin >ULN.
Consumption of methylxanthines (tea, coffee, chocolate), quinine-containing drinks, grapefruit, Seville oranges, poppy seeds, or alcohol within protocol-defined windows before IMP administration.
Investigator judges subject unfit for any reason.
Positive SARS-CoV-2 RT-PCR within 4 weeks prior to screening.
COVID-19 symptoms within 14 days prior to screening.
Severe COVID-19 history (e.g., ECMO, mechanical ventilation).
Unable to attend in-person visits per site COVID guidelines.
Scheduled to receive COVID-19 vaccination within 2 weeks before or after IMP administration.