A Phase 1, Randomized, Placebo-controlled, Double Blind, Single Ascending Dose, First-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS954 in Healthy Male and Female Participants
概览
- 阶段
- 1 期
- 干预措施
- VIS954
- 疾病 / 适应症
- Healthy Volunteers
- 发起方
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
- 状态
- 已完成
- 最后更新
- 8天前
概览
简要总结
This is a first-in-human (FIH), randomized, placebo-controlled, double-blind, single ascending dose (SAD) study to assess the safety and tolerability of VIS954, a monoclonal antibody, in healthy adult male and female participants.
详细描述
The study will be conducted in 6 sequential cohorts. Each cohort will enroll 9 participants, randomized to VIS954 or placebo at a ratio of 7:2. On Day 1, a single dose of VIS954 or placebo will be administered SC. Sentinel participants will be utilized in each cohort. After 14 days, the safety data will be evaluated and a decision to admit and dose the next cohort will be made. The total duration of the clinical study per participant will be up to 102 days (approximately 4 months).
研究者
入排标准
入选标准
- •Male or female participant between 18 to 55 years of age, inclusive, at the screening visit.
- •Non-Japanese participant: Participant does not meet the criteria specified below for 'Japanese Participant'.
- •Japanese participant: Participant is of Japanese descent as evidenced by verbal confirmation of familial heritage (a participant's 4 grandparents were born in Japan and recognized to be 'Japanese').
- •Body mass index between 18.0 and 30.0 kg/m2, inclusive, at the screening visit.
- •Total body weight between 50.0 and 120.0 kg, inclusive, at the screening visit.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol.
- •Willing and able to participate in the study for the defined duration of the study.
- •Female participants will be nonpregnant, nonlactating, and either postmenopausal for at least 1 year or surgically sterile for at least 3 months, or will agree to use highly effective methods of contraception from the period prior to study enrollment until 30 days after Day 56; women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test at screening and a negative urine pregnancy test at baseline prior to administration of the study intervention.
- •Male participants with female partners of childbearing potential must agree to use double barrier contraception or abstain from sex during the study and until 90 days after Day
- •Male participants must agree to refrain from sperm donation for the duration of the study and until 90 days after Day
排除标准
- •Participant has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis, or malignancy. History of minor skin cancers (not including melanoma) or surgically treated, limited cervical carcinomas (ie, carcinoma in situ) are not exclusionary.
- •Participant is participating in another clinical study of any investigational drug, device, or intervention or has received any investigational medication during the last 30 days or 5 half-lives, whichever is longer, before baseline (Day -1).
- •Previous receipt of antibody or biologic therapy.
- •History of a previous hypersensitivity or severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any of the ingredients of the VIS954 SC injection formulation.
- •Blood pressure \> 160/100 mmHg or \< 90/50 mmHg (may be repeated once if abnormal), at the screening visit or Day -
- •History of any infection requiring hospitalization or treatment with antivirals, antibiotics, or systemic antifungals within 3 months prior to screening.
- •Received a vaccination, other than COVID-19 vaccination, during the 30 days prior to administration of the first dose of study intervention. A COVID-19 vaccination cannot be received within 7 days prior to the first dose of study intervention and until 14 days after the last dose.
- •Has received any prescription or nonprescription (over-the-counter) medication during the last 30 days or 5 half-lives, whichever is longer, preceding baseline (Day -1), with the exception of acetaminophen, ibuprofen, naproxen (or other over-the-counter nonsteroidal anti-inflammatory drugs \[NSAID\]), hormonal contraceptives, topical medications, vitamins, and dietary or herbal remedies.
- •Any participant who has a recent history of alcohol or drug/chemical abuse, at the discretion of the investigator, will be excluded.
- •Enrolled participants must abstain from consumption of nicotine containing products from Day -1 through discharge.
研究组 & 干预措施
VIS954 Dose 1
A single VIS954 Dose 1 will be administered subcutaneously on Day 1
干预措施: VIS954
VIS954 Dose 4
A single VIS954 Dose 4 will be administered subcutaneously on Day 1
干预措施: VIS954
Placebo
A single Placebo dose will be administered subcutaneously on Day 1 for 2 participants in each cohort.
干预措施: Placebo
VIS954 Dose 2
A single VIS954 Dose 2 will be administered subcutaneously on Day 1
干预措施: VIS954
VIS954 Dose 6
A single VIS954 Dose 6 will be administered subcutaneously on Day 1
干预措施: VIS954
VIS954 Dose 3
A single VIS954 Dose 3 will be administered subcutaneously on Day 1
干预措施: VIS954
VIS954 Dose 5
A single VIS954 Dose 5 will be administered subcutaneously on Day 1
干预措施: VIS954
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
时间窗: From study intervention administration (Day 1) up to end of follow-up (Day 71)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product or was an important medical event that jeopardized the participant or required medical or surgical intervention to prevent 1 of the other outcomes listed above. TEAEs were AEs that first occurred or worsened in severity after the study intervention administration, and up to Day 71 (including the follow-up period) after the study intervention administration.
Wong-Baker FACES Pain Rating Scale
时间窗: Day 1 (1 and 4 hours post-dose), Day 2 (24 hours post-dose), and on Days 3 and 29
The Wong-Baker FACES Pain Rating Scale was a subjective self-report that was used to record each participant's perception of pain associated with their injection. The scale ranged from 0 to 10 and showed a series of faces ranging from a happy face at 0 which represented "no hurt" to a crying face at 10 which represented "hurts worst." Based on the faces and descriptions, the participant recorded their level of pain. Higher scores indicated more severe pain.
次要结局
- Maximum Serum Concentration (Cmax) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Time of Maximum Serum Concentration (Tmax) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Area Under the Concentration-Time Curve From Pre-dose Extrapolated to Infinite Time (AUC0-inf) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Area Under the Concentration-Time Curve From Pre-dose to the Last Quantifiable Concentration (AUC0-last) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Apparent Terminal Elimination Half-Life (t1/2) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Apparent Volume of Distribution (Vd/F) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Apparent Clearance After Extravascular Dosing (CL/F) of VIS954(Day 1 (within 2 hours pre-dose) and at multiple timepoints post-dose up to Day 71)
- Time Spent Above 40 Percentage Receptor Occupancy (RO) for Neutrophils(Baseline (Day -1) up to Day 71)