A Phase 1 Randomized, Placebo- and Comparator-controlled (Bivalent and Monovalent Components), Observer-blind Study in Older Adults to Evaluate the Safety, Reactogenicity, and Immunogenicity of 3 Dose-levels of VXB-251 (Trivalent), for the Prevention of LRTD Caused RSV, hMPV, PIV3 and to Assess Immunological Interference and Cross-reactivity.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 240
- 试验地点
- 12
- 主要终点
- Proportion of Participants With 1 or More Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and Premature Discontinuation Associated AEs (PDAEs)
研究概览
简要总结
This study is being done to find out how safe and effective a new combined vaccine candidate, called VXB-251, is for older adults. The vaccine candidate is designed to protect against three common viruses that can cause respiratory tract infections:
- RSV (respiratory syncytial virus)
- hMPV (human metapneumovirus)
- PIV3 (parainfluenza virus type 3)
Two components of this vaccine (RSV and hMPV) have already been tested in people before, as part of another study for a two-in-one vaccine. However, this is the first time that the PIV3 component and all three components together (RSV, hMPV, and PIV3) are being tested in people.
The vaccine candidate will be given as a single intramuscular injection. The study will also test unlicensed comparator vaccines and a placebo (a substance that looks like the real vaccine but doesn't contain any active ingredients) that target none, one or two of these viruses to see whether combining all three components affects safety or how well the immune system responds.
详细描述
This is a multicenter randomized, placebo- and comparator-controlled, dose-ranging study to be conducted in Australia in older adults, aged 60 to 83 years, to evaluate the safety, reactogenicity, and immunogenicity of a trivalent RSV/hMPV/PIV3 vaccine candidate, VXB-251. All investigational medicinal products (IMPs) will be administered as a single 0.5 mL intramuscular injection on day 1.
Recruitment will be in 2 stages:
Stage 1 (N=10). Two cohorts, each of 5 participants, will be sequentially enrolled at a 4:1 ratio to receive:
- Cohort 1: either a medium dose of the vaccine candidate or the placebo control,
- Cohort 2: either a high dose of the vaccine candidate or the placebo control
At each enrolling site, at least 1 hour must elapse between IMP injection in the first sentinel and next IMP injection to monitor for hypersensitivity reactions and other fast-onset adverse events (AEs). The investigator or delegate will decide if and when the next sentinel can be vaccinated.
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)
盲法说明
Double
入排标准
- 年龄范围
- 60 Years 至 83 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females aged 60 to 83 years of age at inclusion.
- •Evidence of signed and dated participant informed consent form (PICF) prior to any study procedure, indicating that the subject has been informed of all pertinent aspects of the study.
- •Willingness and ability to comply with the planned study visits and calls, procedures, and restrictions for the duration of the study.
- •Good health, which allows for pre-existing well controlled and low impact chronic diseases, except for the diseases listed in the
排除标准
- •. A disease is defined as well controlled and has a low impact if it did not require meaningful change in therapy or unplanned medical visit(s) in the previous 3 months and allows participant's primary responsibility for self-care and daily living activities.
- •Non-smoker or occasional smoker, defined as smoking less than 10 nicotine-containing cigarettes/ vapes/cigars/pipe fills per week.
- •Contraception and childbearing/conception potential: only female participants with non-childbearing potential will be included. Male participants in a relationship with a female partner of childbearing potential must be willing to use a double contraceptive method together with their female partner for at least 4 weeks before and 12 weeks after the IMP injection at Visit 2 (day 1).
- •Body mass index (BMI) ≥ 17.0 kg/m2 and ≤ 35.0 kg/m
- •Exclusion Criteria:
- •History of RSV, hMPV, and/or PIV3 infection affecting the participant and/or the participant's household in the previous 12 months.
- •History of autoimmune disease (AID) or possibly autoimmune disease (pAID) requiring therapeutic intervention, even if stable and well controlled, including, but not limited to, systemic lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, temporal arteritis, psoriasis, insulin-dependent diabetes mellitus, celiac disease.
- •Confirmed or suspected immunodeficiency, even if stable and well controlled.
- •Ongoing severe asthma. Other allergic diseases (e.g., allergic rhinitis, atopic dermatitis / eczema, mild to moderate asthma, food allergies) are allowed at the investigator's or delegate's discretion.
- •History of significant allergic reaction (e.g., anaphylaxis, hypersensitivity, angioedema) to medication or food or known allergy to vaccine, or any excipients in the formulation, and latex.
- •History of severe AE associated with vaccine administration.
- •Ongoing disorders of coagulation, which contraindicate IM injections.
- •Donation or loss of ≥ 500 mL whole blood on the previous 2 months, and/or donation of plasma in the previous 1 week, and/or intention to donate blood or plasma during the study.
- •Positive serum test results indicating ongoing HIV, HBV and/or HCV infection, and/or documented ongoing HIV, HBV, or HCV infection.
- •Other poorly controlled and/or impactful chronic disease. A disease is defined as poorly controlled if it requires meaningful change in therapy and/or unplanned medical visit(s) in the previous 3 months. A disease is defined as impactful if, in the investigator's judgment, it meaningfully affects the participant's ability to manage self-care and/or activities of daily living.
- •Disease expected to prevent completion of the study (i.e. to rapidly deteriorate within the timeframe of the study).
- •Prior treatments.
- •Receipt of licensed RSV vaccine and/or enrollment in clinical trials(s) evaluating investigational RSV, hMPV, PIV3, and/or molecular clamp-based vaccine candidates at any time, unless it was documented that the participant received a placebo.
- •Other investigational drug or vaccine received in the previous 6 months.
- •Chemotherapy, radiotherapy, and/or other immunosuppressive medication (including biologics) received in the previous 6 months.
- •IgGs or any blood product received in the previous 3 months.
- •Systemic corticosteroids (oral/intravenous/IM) at doses equivalent to ≥ 20 mg prednisone per day received for ≥ 14 days, even if not consecutive, during the previous 3 months. Inhaled/nebulized, intra-articular, intra-bursal, skin, and eye topical corticosteroids are permitted.
- •Received or plan to receive licensed non-live vaccine(s) for the period starting 2 weeks before to 4 weeks after of the study IMP injection or licensed live vaccine(s) for the period starting from 4 weeks before to 4 weeks after the study IMP injection. Pandemic or emergency vaccines are always allowed as per country guidelines.
- •Clinically meaningful abnormal finding from physical examination, vital sign assessment, electrocardiogram (ECG), safety laboratory test results. If deemed appropriate, the investigator or delegate may repeat these assessments.
- •History of alcohol abuse in the previous year determined at the investigator's discretion.
- •History of recreational drug abuse in the previous year and/or positive test for drugs of abuse at Visit 2 (day 1), unless there is an explanation acceptable to the investigator (e.g., the participant has informed in advance that he/she consumed a prescription or over-the-counter product that contained the detected drug).
- •Intention to participate in any investigational drug/vaccine/medical device clinical trial at any time throughout the planned duration of this study.
- •Presence of tattoo, scarring, skin discoloration, or any other skin disturbances at the injection site which may interfere with effective assessment of the injection site.
- •Intention to move to a location that would prevent participating in the study until study end.
- •Any other reason which would prevent the participant from participating in the study or interfere with the participant's compliance with study procedures.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
干预措施: Placebo (Other)
VXB-251, low dose
干预措施: trivalent (RSV/hMPV/PIV3) vaccine candidate (Biological)
VXB-232
干预措施: monovalent (PIV3) unlicensed comparator (Biological)
VXB-251, medium dose
干预措施: trivalent (RSV/hMPV/PIV3) vaccine candidate (Biological)
VXB-251, high dose
干预措施: trivalent (RSV/hMPV/PIV3) vaccine candidate (Biological)
VXB-241
干预措施: bivalent (RSV/hMPV) unlicensed comparator (Biological)
VXB-213
干预措施: monovalent (RSV) unlicensed comparator (Biological)
VXB-221
干预措施: Biological/Vaccine: monovalent (hMPV) unlicensed comparator (Biological)
结局指标
主要结局
Proportion of Participants With 1 or More Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and Premature Discontinuation Associated AEs (PDAEs)
时间窗: 1 month after IMP injection
Proportion of Participants With 1 or More Solicited AEs
时间窗: 7 days after IMP injection
Proportion of Participants With 1 or More Unsolicited Adverse Events (AEs)
时间窗: 1 month after IMP injection
次要结局
- Proportion of Participants With Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and Premature Discontinuation Associated AEs (PDAEs)(6 and 12 months after IMP injection)
- Proportion of Participants With 1 or More Severe Solicited AEs(7 days after IMP injection)
- Geometric Mean Fold Increase (GMFI) of RSV-A, RSV-B, hMPV-A, hMPV-B, and PIV3 Serum Neutralizing Antibody Titers(Pre-injection baseline to 1 month, 6 months, and 12 months, after IMP injection)
- Geometric Mean Titers (GMTs) of RSV-A, RSV-B, hMPV-A, hMPV-B, and PIV3 Serum Neutralizing Antibody Titers(Pre-injection baseline to 1 month, 6 months, and 12 months after IMP injection)
- Proportion of Participants with Sero-response Greater Than or Equal to (>=) 4-fold (SRR-4) and 8-fold (SRR-8) Increase from Baseline in Neutralizing Antibody Titers for RSV-A, RSV-B, hMPV-A, hMPV-B, and PIV3(Pre-injection baseline up to 1 month, 6 months, and 12 months after IMP injection)
- GMFI of RSV PreF, hMPV PreF, and PIV3 PreF Serum Immunoglobulins G (IgG) Concentrations(Pre-injection baseline to 1 month, 6 months, and 12 months after IMP injection)
- Geometric Mean Concentrations (GMC) of RSV PreF, hMPV PreF, and PIV3 PreF Serum IgG(1 month, 6 months, and 12 months after IMP injection)
- Geometric Mean Ratios (GMRs) of Fold Increase of RSV-A and RSV-B Neutralizing Serum Antibody Titers Versus Fold Increase of RSV PreF Serum IgG Concentration(Pre-injection baseline to 1 month, 6 months, and 12 months after IMP injection)
- GMR of Fold Increase of hMPV-A and hMPV-B Neutralizing Serum Antibody Titers Versus Fold Increase of hMPV PreF Serum IgG Concentration(Pre-injection baseline to 1 month, 6 months, and 12 months after IMP injection)
- GMR of Fold Increase of PIV3 Neutralizing Serum Antibody Titers Versus Fold Increase PIV3 PreF Serum IgG Concentration(Pre-injection baseline to 1 month, 6 months, and 12 months after IMP injection)