A Phase 2a Randomized, Observer-blind, Placebo-controlled, Dosage Optimization, Multi-center Clinical Trial to Evaluate the Safety and Immunogenicity of IVX-A12, a Respiratory Syncytial Virus and Human Metapneumovirus Bivalent Combination Virus-like Particle Protein Subunit Vaccine, in Adults 60 to 85 Years of Age
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 264
- 试验地点
- 10
- 主要终点
- Number of Participants With Solicited Local Adverse Reactions (ARs) and Systemic ARs
研究概览
简要总结
The primary purpose of the study is to assess the safety, tolerability and immunogenicity of a bivalent respiratory syncytial virus (RSV)/human metapneumovirus (hMPV) virus-like particle (VLP) candidate vaccine (IVX-A12) compared to placebo, when administered as a single-dose regimen in healthy older adults 60 to 85 years of age.
详细描述
The IVX-A12 Phase 2a clinical trial is a randomized, observer-blind, placebo-controlled, dosage optimization, multi-center trial to evaluate the safety and immunogenicity of a single intramuscular (IM) dose of IVX-A12, with or without adjuvant, in adults 60 to 85 years of age.
Participants will be administered a single shot of IVX-A12, at specified dosage levels, or placebo. The overall duration of the study is up to 1 year (12 months). A subset of participants will be followed for an additional 12 months for a total duration of 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants, who must be in stable health based on medical history, vital signs, physical examination, and laboratory evaluation prior to vaccination, in the investigator's clinical judgment
- •Participants may have ongoing chronic conditions (comorbidities such as hypertension, congestive heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism) who are, in the investigator's opinion, medically compensated and without recent exacerbation within the prior 3 months
- •Participants able to voluntarily give written informed consent and can comply with trial procedures including follow-up for approximately 12 months after vaccination
- •Body mass index 17 to less than (<) 40 kilograms per square meter (kg/m^2) at screening
- •Before randomization, female participants must be unable to conceive (example, menopausal, that is, 12 consecutive months without menstruation, hysterectomy, oophorectomy, etc.) and not intending to conceive by any method
- •Participants must agree not to donate blood from the time of vaccination through 3 months after vaccination
- •Participants must be willing to provide verifiable identification and have the means to be contacted and to contact the investigator or the site's staff during the entire clinical trial
排除标准
- •Participants with moderate or severe liver disease, metastatic solid tumor, and acquired immunodeficiency syndrome (AIDS) are to be excluded. In addition, participants with underlying significant illness or condition(s) or ongoing treatment that, in the opinion of the investigator, could (i) interfere with the conduct of the trial, (ii) pose an unacceptable risk to the participant in this trial, (iii) interfere with the participant's ability to comply with the trial procedures or abide by the procedures
- •Older adults who meet frail elderly criteria (older persons with medical, nutritional, cognitive, emotional, or activity impairments, as defined by the Dalhousie Clinical Frailty Score greater than or equal to [>=]4)
- •Prior receipt of any licensed or investigational RSV or hMPV vaccine within the past 12 months
- •Prior receipt of another investigational medicinal product (IMP; trial drug, biologic, or device) not authorized for use in the United States of America (USA) and European Union within the past 3 months
- •Laboratory-confirmed RSV or hMPV infection within 12 months prior to enrollment
- •Currently enrolled or plan to participate in another clinical trial with an investigational agent (including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) to be received during the trial period
- •History of malignancy within 5 years before screening not in the following categories: (i) participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator, (ii) participants with a history of malignancy within 5 years before screening, with minimal risk of recurrence per investigator's judgment, can be enrolled
- •Acute illness, with or without fever at the time of planned vaccination
- •History of hypersensitivity or serious adverse reactions to vaccines, such as anaphylaxis or angioedema, or any known allergies to any component of the IVX-121 and/or IVX-241 vaccine, or hypersensitivity to latex
- •Abnormal function of the immune system resulting from clinical conditions including chronic administration of systemic corticosteroids (oral/intravenous/IM at a daily dose equivalent of greater than (>) 20 milligram (mg) prednisone in a period of more than 14 days), or administration of immunosuppressive chemotherapy, biologics, or radiotherapy within the past 3 months prior to planned vaccination
- •Participants who have received treatment with immunoglobulins or other biologics, such as immunosuppressive therapies expected to modify immune response to vaccination (including monoclonal antibodies [MAbs] for chronic underlying conditions) within the past 3 months prior to planned vaccination
- •Trial personnel as an immediate family or household member
- •For licensed vaccines:
- •Receipt of licensed inactivated vaccines (including seasonal influenza vaccine) within 14 days prior to trial vaccine administration on Day 0, or licensed replicating vaccines such as ribonucleic acid (RNA) or live-attenuated virus vaccines within 30 days prior to Day 0
- •Receipt of licensed vaccines is permitted after completion of the Day 28 visit
- •Receipt of any licensed Coronavirus Disease-2019 (COVID-19) vaccines is permitted if dosing regimen completed within 21 days prior to Day 0 or after completion of the Day 28 visit.
研究组 & 干预措施
IVX-A12 Vaccine Formulation 1
Participants will receive a single dose of IVX-A12 intramuscular (IM) injection on Day 0.
干预措施: IVX-A12 (Biological)
IVX-A12 Vaccine Formulation 2
Participants will receive a single dose of IVX-A12 IM injection on Day 0.
干预措施: IVX-A12 (Biological)
Placebo
Participants will receive a single dose of placebo IM injection on Day 0.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants With Solicited Local Adverse Reactions (ARs) and Systemic ARs
时间窗: From Day 0 to Day 6
Solicited local ARs include pain, tenderness, erythema, and swelling. Solicited systemic ARs include headache, chills, fatigue, myalgia, arthralgia, vomiting, diarrhea, and fever.
Number of Participants With Unsolicited Adverse Events
时间窗: From Day 0 to Day 28
An unsolicited AE is an AE that was not solicited using the post-vaccination diary and that was spontaneously communicated by a participant.
Model-adjusted Geometric Mean Titers (GMT) for RSV-A, RSV-B, hMPV-A, and hMPV-B-specific Neutralizing Antibodies (NAb)
时间窗: At Day 28
Model-adjusted GMT and corresponding 95% CI were derived from an analysis of covariance (ANCOVA) model of log2 titer at Day 28 with independent variables of log2 baseline titer, age group, and treatment group.
Model-adjusted Geometric Mean Concentrations (GMC) for RSV and hMPV Prefusion F Protein-specific IgG Antibodies (Ab)
时间窗: At Day 28
Model-adjusted GMC and corresponding 95% CI were derived from an analysis of covariance (ANCOVA) model of log2 concentration at Day 28 with independent variables of log2 baseline concentration, age group, and treatment group.
Percentage of Participants With a >=4-fold Increase in Serum RSV-A, RSV-B, hMPV-A, and hMPV-B-specific NAb Titers
时间窗: From Day 0 (pre-vaccination) up to Day 28 post-vaccination
Proportion of participants with non-missing results at the specified visit achieving a 4-fold or greater increase in NAb titer versus baseline (Day 0).
Percentage of Participants With >=4-fold Increase in RSV and hMPV-specific IgG Ab Concentration
时间窗: From Day 0 (pre-vaccination) up to Day 28 post-vaccination
Proportion of participants with non-missing results at the specified visit achieving a 4-fold or greater increase in Ab concentration versus baseline (Day 0).
Geometric Mean Fold Rise (GMFR) in Serum for RSV-A, RSV-B, hMPV-A, and hMPV-B-Specific NAb Titers
时间窗: From Day 0 (pre-vaccination) up to Day 28 post-vaccination
GMFR is defined as the geometric mean of the ratio of NAb titer at specified timepoints after vaccination divided by baseline (Day 0) titer.
Geometric Mean Fold Rise (GMFR) in Serum for RSV and hMPV Prefusion F Protein-specific IgG Ab Concentrations
时间窗: From Day 0 (pre-vaccination) up to Day 28 post-vaccination
GMFR is defined as the geometric mean of the ratio of Ab concentration at specified timepoints after vaccination divided by baseline (Day 0) concentration.
次要结局
- Number of Participants With Serious Adverse Event (SAE), Medically-attended Adverse Events (MAAEs), and AEs Leading to Trial Withdrawal(From Day 0 up to the end of study (up to Day 365))
- Number of Participants With Mild, Moderate, or Severe Lower Respiratory Tract Illness (LRTI) Caused by RSV and/or hMPV(From Day 0 up to Day 365 (end of study))
- Number of Participants With Mild, Moderate, or Severe LRTI Cases Not Caused by RSV or hMPV(From Day 0 up to Day 365 (end of study))
- Number of Participants With Clinically Significant Safety Laboratory Parameters(At Screening, Days 0, 7 and 28)
- Model-Adjusted GMTs for RSV-A, RSV-B, hMPV-A, and hMPV-B-specific NAb(At Days 180 and 365)
- Model-Adjusted GMCs for RSV and hMPV Prefusion F Protein-specific IgG Ab Concentrations(At Days 180, and 365)
- Percentage of Participants With a >=4-fold Increase in Serum RSV-A, RSV-B, hMPV-A, and hMPV-B-specific NAb Titers(From Day 0 (pre-vaccination) up to Day 180 and Day 365 post-vaccination)
- Percentage of Participants With >=4-fold Increase in RSV and hMPV Prefusion F Protein-specific IgG Ab Concentrations(From Day 0 (pre-vaccination) up to Days 180, and 365 post-vaccination)
- Percentage of Participants With a >=8-fold Increase in Serum RSV-A, RSV-B, hMPV-A, and hMPV-B-specific NAb Titers(From Day 0 (pre-vaccination) up to Days 28, 180, and 365 post-vaccination)
- GMFR in Serum for RSV-A, RSV-B, hMPV-A, and hMPV-B-specific NAb Titers and RSV and hMPV Prefusion F Protein-specific IgG Ab Concentrations(From Day 0 (pre-vaccination) up to Day 180 and Day 365 post-vaccination)
- Reverse Cumulative Distribution (RCD) Curve of Serum NAb Titers and IgG Ab Concentrations(At Days 28, 180, and 365 post-vaccination)