A Phase 1/2, Randomized, Single Ascending Dose Study in Adults (Stage 1) and Randomized, Single Ascending Dose-Finding Study (Stage 2) in Elderly Subjects With ASP3772, a Pneumococcal Vaccine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 630
- 试验地点
- 48
- 主要终点
- Number of Participants With Clinically Significant Abnormalities in Vital Signs
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of 3 different dose levels of ASP3772 in comparison to the active comparator Prevnar 13® (PCV13) in adults 18 to 64 years of age in Stage 1. Stage 2 will evaluate the safety, tolerability, and immunogenicity of 3 different dose levels of ASP3772 in comparison to the active comparator PCV13 in elderly 65 to 85 years of age. In addition, Stage 2 will evaluate the immunogenicity of 3 different dose levels of ASP3772 relative to the response seen following administration of Pneumovax® 23 (PPSV23) for the serotypes not included in PCV13.
详细描述
The study population will consist of 3 different groups: Group 1 - Stage 1 PCV13 naïve participants randomized within 3 sequential cohorts to ASP3772 or PCV13; Group 2 - Stage 2 PCV13 naïve participants randomized within 3 sequential cohorts to ASP3772 or PCV13; and Group 3 - Stage 2 participants previously vaccinated with PCV13 that will receive PPSV23.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Stage 1: Subject is healthy male or female between 18 and 64 year of age inclusive, at screening.
- •Stage 2: Subject is a male or female between 65 and 85 years of age, inclusive, at screening who is healthy or has chronic controlled, stable disease with no change in disease severity, medical therapy and no hospitalization records in last 12 weeks as determined by medical history, physical examination and laboratory data.
- •A female subject is eligible to participate if not pregnant and at least 1 of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP) OR
- •WOCBP who agrees to follow the contraceptive guidance at screening and for at least 28 days after the study vaccine administration.
- •Female subject must agree not to breastfeed starting at screening and for 28 days after the study vaccine administration.
- •Female subject must not donate ova starting at screening and for 28 days after the study vaccine administration.
- •A male subject with female partner(s) of childbearing potential must agree to use contraception at screening and for at least 28 days after the study vaccine administration.
- •Male subject must not donate sperm starting at screening and for 90 days after the study vaccine administration.
- •Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding at screening and for 28 after the study vaccine administration.
- •Subject agrees not to participate in another interventional study while participating in the present study.
排除标准
- •Subject has a known or suspected hypersensitivity to ASP3772, its comparators or any components of the formulations used.
- •Subject has had previous exposure with ASP
- •Subject has had known previous exposure with PPSV
- •Subject has received PCV13 or any other licensed or investigational pneumococcal vaccine at any time. (Note: This exclusion criterion is not applicable to Group 3; those subjects 65 to 85 years of age who previously received immunization with PCV
- •Prior PCV13 immunization should have taken place no less than 10 months and no more than 2 years prior to study vaccine administration. These subjects are eligible to be enrolled in the nonrandomized arm of Stage 2, Group
- •Subject has a history of microbiologically-proven invasive disease caused by S. pneumoniae.
- •Subject has an immune disorder(s) (including autoimmune disease) and/or clinical conditions requiring immunosuppressive drugs.
- •Subject has any evidence of any unstable or active clinically significant cardiovascular, gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, e.g., uncontrolled hypertension, uncontrolled diabetes, heart failure, uncontrolled chronic obstructive pulmonary disease, end-stage renal disease.
- •Subject has history of illicit drug(s) or alcohol abuse that will interfere with the protocol requirements and/or a positive urine drug test (for Stage 1 subjects only) at screening.
- •Subject has any clinically significant history of allergic conditions including drug allergies, asthma or anaphylactic reactions, but excluding untreated asymptomatic seasonal allergies prior to study vaccine administration.
- •Subject has a coagulation disorder contraindicating intramuscular immunization.
- •Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies (anti-HCV) confirmed by reflex testing (HCV-RNA) or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
- •Subject has/had febrile illness (> 100.4°F oral equivalent) or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day
- •Subject has any clinically significant abnormality from the physical examination, ECG and clinical laboratory tests during screening.
- •Subject is unlikely to adhere to study procedures, keep appointments, is planning to relocate during the study or cannot be adequately followed for safety according to the protocol.
- •Subject has any other condition, which precludes the subject's participation in the study.
- •Subject has received any vaccines within 30 days prior of receipt of the study vaccine (exception: Influenza virus vaccine given according to recommended guidelines must be given at least 7 days prior to receiving study vaccine).
- •Subject has had significant blood loss, donated 1 unit (450 mL or more) or received transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to day
- •Subject has received any systemically absorbed antibiotics during the 7-day period prior to day 1.
结局指标
主要结局
Number of Participants With Clinically Significant Abnormalities in Vital Signs
时间窗: During first hour post vaccination (vaccine administered at Day 1)
Vital signs parameters included blood pressure (hypotension and hypertension), pulse rate (tachycardia and bradycardia), body temperature and respiratory rate. Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Number of Participants With TEAEs, [Stage 2, Group 3]
时间窗: From Day 1, Up to Day 30
An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature.
Reactogenicity Assessed by Number of Solicited Systemic Reactions, [Stage 1, Group 1]
时间窗: Up to 7 Day post Vaccination (vaccine administered at Day 1)
Assessed systemic reactions were nausea/vomiting, diarrhea, headache, fever, fatigue and muscle discomfort or pain/myalgia.
Number of Participants With Potentially Clinically Significant Laboratory Values
时间窗: Up to Day 30
Clinical laboratory testing included hematology, clinical chemistry, or urinalysis. Any abnormal laboratory test result (e.g., in hematology, clinical chemistry, or urinalysis) that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Laboratory tests of clinical interest included total bilirubin ≥ 2x ULN and Alkaline phosphatase \> 1.5 × upper limit of normal. Study Investigator's interest was to assess only potentially clinically significant values.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 1, Group 1] and [Stage 2, Group 2]
时间窗: At Day 7
The Investigator assessed standard 12-lead ECG recordings for the purposes of safety assessment and participant management. Any clinically significant abnormality, as determined by the investigator's medical and scientific judgment and unrelated to underlying disease, should be reported as an unsolicited (S)AE. Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Reactogenicity Assessed by Number of Solicited Systemic Reactions [Stage 2, Group 2 and Group 3]
时间窗: Up to 7 Day post Vaccination (vaccine administered at Day 1)
Assessed systemic reactions were nausea/vomiting, diarrhea, headache, fever, fatigue and muscle discomfort or pain/myalgia.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG), [Stage 2, Group 3]
时间窗: Day - 28 to Day -1 (28 days prior to study vaccination)
The Investigator assessed standard 12-lead ECG recordings for the purposes of safety assessment and participant management. Any clinically significant abnormality, as determined by the investigator's medical and scientific judgment and unrelated to underlying disease, should be reported as an unsolicited (S)AE. Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Reactogenicity Assessed by Number of Solicited Local Reactions, [Stage 2, Group 2 and Group 3]
时间窗: Up to 7 Day post Vaccination (vaccine administered at Day 1)
Assessed solicited local reactions were pain, tenderness, redness/erythema, swelling, induration, itching at injection site and pruritus at injection site.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), [Stage 1, Group 1]
时间窗: From Day 1, Up to Day 180
An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature.
Number of Participants With TEAEs, [Stage 2, Group 2]
时间窗: From Day 1, Up to Day 180
An AE is any untoward medical occurrence in a participant administered a study vaccine, and which does not necessarily have to have a causal relationship with this vaccination. A TEAE is defined as any AE with onset within 30 days from study vaccine administration. Medically attended TEAEs (MAAEs) are AEs for which the participant has received medical attention by medical personnel, or in an emergency room, or which led to hospitalization. A new-onset chronic disease TEAEs (NOCD) is defined as a MAAE which a) was absent at baseline; b) has not resolved at the follow-up telephone call; c) requires continuous medical care or attention. Potentially Immune Mediated medical condition TEAEs (PIMMCs) are defined as any AEs of autoimmune or auto inflammatory nature. As specified in protocol, data was planned to be analyzed for PCV13 pooled comparator from each group given PCV13 to compare with each ASP3772 dose.
Number of Participants With Potentially Clinically Significant Physical Examination Values
时间窗: Up to Day 30
A physical examination consists of an examination of general appearance, eyes, nose throat, neck (including thyroid), lymph nodes, chest, lungs, cardiovascular, abdomen, skin, extremities, musculoskeletal and neurological system including mental status. Any abnormal test result that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Study Investigator's interest was to assess only potentially clinically significant values.
Reactogenicity Assessed by Number of Participants With Solicited Local Reactions, [Stage 1, Group 1]
时间窗: Up to 7 Day post Vaccination (vaccine administered at Day 1)
Local reactions include pain, tenderness, redness/erythema, swelling and induration.
次要结局
- GMFR for Unique Serotypes IgG, [Stage 2, Group 2](At Day 30)
- Geometric Mean Titers (GMTs) for Serotype-specific Opsonophagocytic Activity (OPA) Titer, [Stage 1, Group 1](At Day 1 and Day 30)
- Geometric Mean Concentration (GMCs) for Serotype-specific Immunoglobulin G (IgG), [Stage 1, Group 1](At Day 1 and Day 30)
- GMCs for Serotype-specific IgG, [Stage 2, Group 2](At Day 1 and Day 30)
- Percentage of Participants With Unique Serotypes IgG of Greater Than or Equal to (>=) 4-fold Increase, [Stage 1, Group 1](At Day 30)
- Dose Response in OPA Titer for ASP3772 (Stage 2, Group 2)(At Day 30)
- GMTs for Serotype-specific OPA Titer, [Stage 2, Group 2](At Day 1 and Day 30)
- Dose Response in the IgG Concentrations for ASP3772 [Stage 2, Group 2](At Day 30)
- GMCs for Unique Serotypes IgG, [Stage 2, Group 2 and Group 3](At Day 30)
- Geometric Mean Fold Rise (GMFR) for Unique Serotypes IgG [Stage 1, Group 1](At Day 30)
- GMTs for Unique Serotype OPA Titer, [Stage 1, Group 1](At Day 30)
- Percentage of Participants With Unique Serotype-specific IgG Concentration of Greater Than or Equal to (>=) 4-fold Increase, [Stage 2, Group 2](At Day 30)
- GMTs for Unique Serotype OPA Titer [Stage 2, Group 2 and Group 3](At Day 30)