Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of a Subcutaneously- and Orally- Administered Supplemental Spike & Nucleocapsid-targeted COVID-19 Vaccine to Enhance T Cell Based Immunogenicity in Participants Who Have Already Received Prime + Boost Vaccines Authorized For Emergency Use
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs
研究概览
简要总结
This is a phase 1/2 study in adult healthy subjects that have previously been vaccinated with an FDA-authorized vaccine against COVID-19. This clinical trial is designed to assess the safety, efficacy, reactogenicity, and immunogenicity of hAd5-S-Fusion+N-ETSD formulated for subcutaneous and oral (capsule) administration.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults, age ≥ 18 years, inclusive, at time of enrollment, that have previously received an FDA-authorized COVID-19 vaccine (both prime and boost) ≥14 days and
- •≤ 6 months before enrollment.
- •Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
- •Agrees to the collection of biospecimens (eg, NP swabs and/or saliva sample) and venous blood per protocol.
- •Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
- •Ability to swallow a capsule.
- •Temperature < 38°C.
- •Agreement to practice effective contraception for female subjects of childbearing potential and non-sterile males. Female subjects of childbearing potential must agree to use effective contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile male subjects must agree to use a condom while on study until at least 1 month after the last dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, IUDs, oral contraceptives, and abstinence.
排除标准
- •Persistent grade ≥ 2 AEs related to previous COVID-19 vaccination at the time of enrollment.
- •Allergy to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past.
- •Pregnant and nursing women. A negative serum or urine pregnancy test during screening and on the day of and prior to each dose must be documented before the vaccine is administered to a female subject of childbearing potential.
- •Chronic lung disease including chronic obstructive pulmonary disease (COPD) or moderate to severe asthma.
- •Pulmonary fibrosis.
- •Bone marrow or organ transplantation.
- •Extreme obesity (defined as BMI of 35 kg/m2 or higher).
- •Chronic kidney disease.
- •Liver disease.
- •Sickle cell disease.
- •Thalassemia.
- •Any disease associated with acute fever, or any infection.
- •Self-reported history of SARS.
- •History of hepatitis B or hepatitis C.
- •HIV or other acquired or hereditary immunodeficiency.
- •Serious cardiovascular diseases, such as heart failure, coronary artery disease, cardiomyopathies, arrhythmia, conduction block, myocardial infarction, pulmonary hypertension, severe hypertension without controllable drugs, etc.
- •Cerebrovascular disease.
- •Cystic fibrosis.
- •Neurologic conditions, such as dementia.
- •Hereditary or acquired angioneurotic edema.
- •No spleen or functional asplenia.
- •Platelet disorder or other bleeding disorder that may cause injection contraindication.
- •Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness within 3 months before administration of study vaccine. (Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.)
- •Prior administration of blood products in last 4 months.
- •Currently receiving treatment for cancer or history of cancer in the last five years (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- •According to the judgement of investigator, various medical, psychological, social or other conditions that could affect the subjects ability to sign informed consent.
- •Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
研究组 & 干预措施
Experimental: Cohort 1: hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous
Cohort 1 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous on Day 1
干预措施: hAd5-S-Fusion+N-ETSD vaccine (Biological)
Experimental: Cohort 2: hAd5-S-Fusion+N-ETSD Subcutaneous and Oral
Cohort 2 (n=20): hAd5-S-Fusion+N-ETSD at 5 × 10e10 IU/dose Subcutaneous and 1 × 10e10 IU/dose Oral on Day 1
干预措施: hAd5-S-Fusion+N-ETSD vaccine (Biological)
结局指标
主要结局
Phase 1 Safety: Incidence and severity of solicited local reactogenicity AEs
时间窗: through 1 week post final vaccine administration
Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Incidence and severity of solicited systemic reactogenicity AEs
时间窗: through 1 week post final vaccine administration
Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration
Phase 1 Safety: Vital Sign - Blood Pressure
时间窗: Day 365
Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg
Phase 1 Safety: Vital Sign - Respiratory Rate
时间窗: Day 365
Changes in vital signs from Grades 1-4: measured in how many breaths per minute
Phase 1 Safety: Incidence of MAAEs and SAEs
时间窗: 6 months post final vaccine administration
Incidence of MAAEs and SAEs at 6 months post final vaccine administration
Phase 1 Safety: Incidence of changes of laboratory safety examinations
时间窗: Day 365
Incidence of abnormal changes of laboratory safety examinations
Phase 1 Safety: Vital Sign - Temperature
时间窗: Day 365
Changes in vital signs from Grades 1-4: measured in (°C) or (°F)
Phase 1 Safety: Vital Sign - Heart Rate
时间窗: Day 365
Changes in vital signs from Grades 1-4: measured by how many heart beats per minute
Phase 1 Safety: Incidence and severity of unsolicited AEs
时间窗: through 30 days post final vaccine administration
Incidence and severity of unsolicited AEs through 30 days post final vaccine administration
Phase 2 Efficacy: Percent of subjects that show an increase in N-reactive T cells
时间窗: from baseline to Day 365
Percent of subjects that show an increase in N-reactive T cells as assayed by N-Tiferon assay (≥ 25 pg/mL increase in cytokine concentration from baseline)
次要结局
- Phase 2 Safety: Incidence of changes of laboratory safety examinations(Day 365)
- Phase 2 Safety: Vital Sign - Heart rate(Day 365)
- Phase 2 Safety: Vital Sign - Blood Pressure(Day 365)
- Phase 2 Efficacy: Humoral Immunogenicity - GMT of S-specific and N-specific antibodies(Day 365)
- Phase 2 Efficacy: Mucosal Immunogenicity - GMT of IgA antibody levels(Day 365)
- Phase 2 Safety: Incidence and severity of solicited systemic reactogenicity AEs(through 1 week post final vaccine administration)
- Phase 1 Humoral Immunogenicity: GMT of S-specific and N-specific antibodies(Day 365)
- Phase 1 Humoral Immunogenicity: GMT of neutralizing antibody(Day 365)
- Phase 2 Efficacy: Humoral Immunogenicity - GMT of neutralizing antibody(Day 365)
- Phase 2 Efficacy: Cellular Immunogenicity - T cell activity(Day 365)
- Phase 2 Safety: Incidence and severity of solicited local reactogenicity AEs(through 1 week post final vaccine administration)
- Phase 2 Safety: Incidence and severity of unsolicited AEs(through 30 days post final vaccine administration)
- Phase 2 Safety: Vital Sign - Respiratory rate(Day 365)
- Phase 2 Efficacy: Mean SARS-CoV-2 viral load(Day 365)
- Phase 2 Efficacy: Incidence and severity of COVID-19 ≥14 days after vaccination(≥14 days after vaccination)
- Phase 2 Safety: Incidence of MAAEs and SAEs(through 30 days and 6 months post final vaccine administration)
- Phase 2 Safety: Vital Sign - Temperature(Day 365)
- Phase 1 Cellular Immunogenicity: T cell activity(Day 365)
- Phase 1 Mucosal Immunogenicity: GMT of IgA antibody levels(Day 365)