A Phase I, Randomized, Observer-Blinded, Placebo-Controlled, Single and Multiple Ascending-Dose Study to Investigate the Safety, Pharmacokinetics, and Immunogenecity of BITS7201A in Healthy Volunteers and Patients With Mild Atopic Asthma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Percentage of Participants with Adverse Events (AEs)
研究概览
简要总结
This randomized, observer-blinded, placebo-controlled, single and multiple ascending-dose study will be conducted in two parts to evaluate the safety, pharmacokinetics, and immunogenicity of BITS7201A. Part A will be an ascending, single-dose, sequential-group study where participants will be randomly assigned to active drug or placebo. Part B will be an ascending, multiple-dose, sequential-group study where participants will be randomized to active drug or placebo. Total length of the study is anticipated to be approximately 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General Inclusion Criteria:
- •Body mass index between 18 and 37 kilograms per meter square (kg/m^2)
- •Weight 50-120 kilograms
- •Participants in good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
- •Clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the Investigator and Sponsor.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method for at least 70 days after the last dose of study drug
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm for at least 70 days after the last dose of study drug
- •Additional Inclusion Criteria for Participants With Mild Atopic Asthma:
- •Diagnosis of asthma for greater than or equal to (>/=) 3 months prior to screening
- •History of atopy
- •Pre-bronchodilator forced expiratory volume in 1 second (FEV1) >/=60 percent (%) predicted at screening
- •Fractional exhaled nitric oxide (FeNO) >/=30 parts per billion (ppb) at screening and at randomization (predose)
排除标准
- •General Exclusion Criteria:
- •History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, gastrointestinal, urologic, neurologic, or psychiatric disorders
- •History of hematologic or immunosuppressive disorders
- •History of severe depression or suicidal ideation
- •History of inflammatory bowel disease
- •History of anaphylaxis, hypersensitivity, or significant drug allergies
- •History or presence of an abnormal ECG, which is clinically significant
- •History of a positive tuberculin skin test in participants who are Bacille Calmette-Guérin (BCG) vaccine naïve or history of a positive interferon-gamma release assay in participants who have received the BCG vaccine
- •Participants with neutropenia or thrombocytopenia
- •History of alcoholism or drug addiction within 1 year of screening
- •Self-reported history of smoking (tobacco, marijuana, or vaping) within the 7 days prior to initiation of study drug
- •Smokers not able to pass the tobacco-related laboratory screening and who cannot refrain from smoking during the confinement periods
- •Pregnancy or lactation
- •History of malignancy, except completely excised basal cell carcinoma or squamous cell carcinoma of the skin
- •Any severe bacterial, fungal, or parasitic infections associated with hospitalization or IV antibiotics within 1 year of screening
- •History of active parasitic infection within 6 months or exposure to water-born parasites within 6 weeks prior to initiation of study drug
- •Upper or lower respiratory tract infection within 4 weeks prior to screening
- •Received oral antibiotics within 4 weeks prior to initiation of study drug, or IV/intramuscular (IM) antibiotics within 8 weeks prior to initiation of study drug
- •For health volunteers: use of any prescription medications/products within 7 days prior to Day 1 and throughout the study
- •Use of any immunosuppressive medication within 30 days or 5 half-lives, whichever is greater, prior to initiation of study drug
- •Use of a non-biologic investigational drug or participation in an investigational study with a non-biologic drug within 30 days prior to initiation of study drug (or within 5 half-lives of the investigational product, whichever is greater)
- •Use of a biologic investigational therapy or participation in an investigational study involving biologic therapy within 3 months or 5 half-lives, whichever is greater, prior to initiation of study drug
- •Received live or attenuated vaccine within 30 days prior to screening
- •Received killed vaccine within 14 days prior to initiation of study drug, unless deemed acceptable by the investigator and Sponsor
- •Positive blood test for chronic viral infections by: hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody
- •Additional Exclusion Criteria for Participants With Mild Atopic Asthma:
- •Poorly controlled asthma
- •Use of any prescription medications and/or products other than asthma and/or allergic rhinitis medications within 7 days prior to Day 1 and throughout the study, unless deemed acceptable by the investigator and Sponsor
- •Active lung disease other than asthma
- •Occupations with potential exposure to exogenous sources of nitrous oxide and/or associated with elevated FeNO
- •Unable to perform FeNO measurement
研究组 & 干预措施
Part A Cohort A: BITS7201A Dose Level 1 Subcutaneous (SC)
Healthy participants will receive a single SC dose of BITS7201A dose Level 1 on Day 1.
干预措施: BITS7201A (Drug)
Part A Cohort B: BITS7201A Dose Level 2 SC
Healthy participants will receive a single SC dose of BITS7201A dose Level 2 on Day 1.
干预措施: BITS7201A (Drug)
Part A Cohort C: BITS7201A Dose Level 4 SC
Healthy participants will receive a single SC dose of BITS7201A dose Level 4 on Day 1.
干预措施: BITS7201A (Drug)
Part A Cohort D: BITS7201A Dose Level 4 Intravenous (IV)
Healthy participants will receive a single IV dose of BITS7201A dose Level 4 on Day 1.
干预措施: BITS7201A (Drug)
Part A Cohort E: BITS7201A Dose Level 6 IV
Healthy participants will receive a single IV dose of BITS7201A dose Level 6 on Day 1.
干预措施: BITS7201A (Drug)
Part A: Placebo
Healthy participants will receive a single SC or IV dose of placebo matched to BITS7201A on Day 1.
干预措施: Placebo (Drug)
Part B Cohort F: BITS7201A Dose Level 3 SC
Healthy participants will receive a single SC dose of BITS7201A dose Level 3 every 4 weeks (Q4W) on Days 1, 29, and 57.
干预措施: BITS7201A (Drug)
Part B Cohort G: BITS7201A Dose Level 4 SC
Healthy participants will receive a single SC dose of BITS7201A dose Level 4 Q4W on Days 1, 29, and 57.
干预措施: BITS7201A (Drug)
Part B Cohort H: BITS7201A Dose Level 5 SC
Healthy participants will receive SC dose of BITS7201A dose Level 5 Q4W on Days 1, 29, and 57.
干预措施: BITS7201A (Drug)
Part B Cohort I:BITS7201A Dose Level 5 SC (Mild Atopic Asthma)
Mild atopic asthma participants will receive SC dose of BITS7201 dose Level 5 Q4W on Days 1, 29, and 57.
干预措施: BITS7201A (Drug)
Part B: Placebo
Healthy participants or mild atopic asthma participants will receive SC doses of placebo matched to BITS7201A Q4W on Days 1, 29, and 57.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs)
时间窗: Baseline up to end of the study (Approximately 12 months)
Number of Participants with Anti-Therapeutic Antibodies (ATA) to BITS7201A and Associated Clinical Sequelae
时间窗: Baseline up to end of the study (Approximately 12 months)
次要结局
- Area under the Concentration-Time Curve (AUC) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))
- Half-Life (t1/2) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))
- Maximum Observed Serum Concentration (Cmax) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))
- Total Clearance (CL/F) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))
- Number of Participants with Impact of ATA Status(Baseline up to end of the study (Approximately 12 months))
- Apparent Volume of Distribution (Vz/F) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))
- Bioavailability (Percentage of Administered Dose Reaching the Systemic Circulation) of BITS7201A(Part A: predose on Day 1; Days 2, 5, 8, 15, 29, 43, 57, 85; 0.5, 2 hours postdose (for IV only) on Day 1; Part B: predose on Days 1, 29, 57; on Days 5, 8 15, 61, 71, 85, 113, 141 (predose: 0 hour; IV infusion duration = 15 approximately minutes))