Dose-escalation, Open-label, Non-randomized Phase I Study to Evaluate the Safety and Immunogenicity of Three Concentrations of a rNDV Vaccine Against SARS-CoV-2 Administered by the Intranasal and Intramuscular Route to Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Safety: Pregnancy test
研究概览
简要总结
This is a Phase 1, open-label, non-randomized, dose-escalation study using three doses and two schemes of administration of a recombinant vaccine against SARS-CoV-2 based on a viral vector (Newcastle Disease virus) in 90 healthy volunteers at a single research site in Mexico City.
详细描述
The lack of highly effective treatments against COVID-19 and the social and economic impact that the current pandemic has exerted on public health highlights the uncontested importance of developing vaccines that, in addition to their safety and ability to induce a protective response, are logistically suitable for massive administration across a variety of countries and settings.
This is the first clinical study of the development program of a vaccine based on a unique recombinant viral vector technology that has been successful in the design of avian vaccines and that has no contraindication for use in humans.
The recombinant vaccine subject to research in this study is based on an active viral vector of a recombinant Newcastle Disease virus (rNDV) LaSota strain, in which the gene that codes for the S glycoprotein of SARS-CoV-2 has been inserted.
The Newcastle Disease Virus (NDV) is a paramyxovirus responsible for the Newcastle Disease in birds. There are three main families of NDV according to the level of virulence. The one with the lowest virulence is the lentogenic group. One lentogenic viral strain is LaSota (NDV_LS), which is broadly used in the development of avian vaccines. The LaSota strain seems to replicate only at the site of inoculation and, although it does not reach the lymph nodes, it reduces the induction of pro-inflammatory cytokines while boosting a robust protective immune response. Very importantly, this virus cannot insert itself into the human genome.
One of the key factors for an increased virulence in NDV is the activation of the cleavage site that corresponds to the protein F precursor phenotype. In highly virulent strains, the cleavage is performed by ubiquitous intracellular proteins, which leads to a widespread replication in birds.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult men and women ≥18 year-old and ≤55-year-old.
- •Signed informed consent.
- •No respiratory disease within last 21 days prior to first dose administration.
- •Body Mass Index from 18.0 to 29.0 kg/m
- •Negative RT-PCR for SARS-Cov-2 infection.
- •Negative test for anti-SARS-CoV-2 IgM and IgG antibodies.
- •O2 saturation ≥92% by pulse oximetry.
- •Normal CT scan of thorax.
- •No symptoms from clinical history and normal physical exam at screening visit.
- •Lab test values within normal ranges for all the following:
- •Urinalysis. Liver enzymes. Renal function tests. Cholesterol and Triglycerides. Fasting glucose. Hematology.
- •Negative test for HBsAg, anti-HCV and anti-HIV antibodies. Negative VDRL test.
- •Normal electrocardiogram.
- •Negative pregnancy test for women with childbearing potential.
- •Agreement of all sexually- active volunteers to use highly effective contraceptives over the study period and up to 30 days after the last administration of the experimental vaccine.
- •Commitment from all participants to keep social distancing, use of mask and frequent hand washing with soap or antibacterial gel during the study period.
排除标准
- •History of hypersensitivity or allergy to any ingredient of the vaccine.
- •History of severe anaphylactic reaction.
- •History of seizures.
- •History of chronic diseases or cancer.
- •Vaccination against SARS-CoV-2 with approved or experimental vaccines.
- •Participation in any other study with an experimental intervention within the last 3 months.
- •Administration of any other drug or herbal preparation within the last 30 days.
- •Any vaccine administered within the last 30 days, including influenza vaccine.
- •Fever at the time of entry.
- •Blood transfusion or blood components transfusion within the last 4 months.
- •Regular activity related to work, social interaction or entertainment that represents an exposure to SARS-Cov-2 higher than that of the general population, as per investigator judgement.
- •Drug and alcohol abuse.
- •Any medical or not medical condition that could interfere with patient safety, study compliance or data interpretation, as per investigator judgement.
结局指标
主要结局
Safety: Pregnancy test
时间窗: Day 14
Blood hCG
Safety: Oxygen saturation
时间窗: Day 14
Pulse oximetry (%)
Safety: adverse events
时间窗: Day 365
Incidence of adverse events
Safety: Urinalysis
时间窗: Day 14
Qualitative and by sediment examination
次要结局
- Titers of circulating anti-SARS-CoV2 antibodies(Day 90 after application)
- Titers of neutralizing anti-SARS-Cov-2 antibodies(Day 90 after application)
- Titers of mucosal IgA(Day 365)
- T-cell elicited responses(Day 365)
- Titers of secretory IgA(Day 42 after application)