Phase I/II Study to Evaluate Safety, Tolerability, and Immunogenicity of a Prophylactic Plasmid DNA Vaccine Against SARS-CoV-2 [Covigenix VAX-001/VAX-001-1b] in Healthy Adults 18 Years and Older
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 268
- 试验地点
- 4
- 主要终点
- Safety of a 2-dose regimen of VAX-001 when doses are given 14 days apart
研究概览
简要总结
This study is a Phase I/II clinical study in healthy adults designed to assess the safety, tolerability, and immunogenicity of receiving 2 IM injections of Covigenix VAX-001/-1b, 28 days apart. Covigenix VAX-001/-1b is a plasmid DNA vaccine that expresses key antigenic determinants from SARS-CoV-2 and uses Entos Pharmaceuticals' Fusogenix PLV platform.
The phase I part of this study was completed in Canada. The phase II part of the study will be completed in Burkina Faso, Senegal and South Africa.
详细描述
Phase I portion of the study:
Study design:
ENTVAX01-101 is a phase I/II, placebo-controlled, randomized, observer-blind, dose ranging clinical trial in males and non-pregnant females, 18 years and older, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, tolerability, and immunogenicity of Covigenix VAX-001 manufactured by Entos Pharmaceuticals. Covigenix VAX-001 is a novel plasmid DNA-based vaccine that encodes for the full-length Spike protein from SARS-CoV-2 (VAX-001 encapsulated in a proprietary Fusogenix Proteo-Lipid Vehicle (PLV)).
Enrollment for the phase I portion of the study will occur at one Canadian site. Thirty-six participants will be enrolled in a staggered manner into one cohort an 3 groups (0.100 mg & 0.250 mg vs. placebo) in stage I. Participants will receive an intramuscular (IM) injection (0.5 milliliter [mL]) on Days 0 and 14 in the deltoid muscle of alternating arms and will be followed through 12 months post booster vaccination (Day 379). Follow-up visits will occur at Days 7, 14, 17, 21, 28, 42, 196, and 379.
The primary objective is to evaluate the safety of a 2-dose vaccination schedule of the Covigenix VAX-001 vaccine, given 14 days apart. The secondary objectives are to evaluate the humoral immune response as measured by Immunoglobulin G (IgG) ELISA to the SARS-CoV-2 S protein and by pseudo-viral neutralization assay to pseudo-virion following a 2-dose vaccination schedule of Covigenix VAX-001.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Unblinded study nurse with no other role in the trial administers VAX-001. Observer blinded.
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for Phase I:
- •Each participant must meet all of the following criteria to be enrolled in the Phase 1 part of the study:
- •The participant is a healthy adult from 18 <55 years and with a BMI of ≤30 kg/m2 at the time of enrollment.
- •If the participant is a WOCBP, she must have practiced adequate contraception for 30 days prior to IP Dose 1, have a negative pregnancy test on the day of IP Dose 1, and have agreed to continue adequate contraception until 90 days after IP Dose
- •If the participant is male, he must agree to continue adequate contraception until 90 days after IP Dose
- •The participant is able to provide consent to participate in the study and has signed an ICF.
- •The participant is able and willing to complete all the scheduled study procedures during the whole study period (approximately 13 months).
- •The participant is generally in good health, as determined by a review of medical history and a physical examination within 14 days prior to IP Dose
- •Inclusion criteria for Phase II
- •Each participant must meet all of the following criteria to be enrolled in Phase II part of the study:
- •The participant is 18 years and older.
- •If the participant is a WOCBP, she must have a negative pregnancy test on the day of IP Dose 1, and have agreed to adequate contraception until 90 days after IP Dose 2 administration.
- •If the participant is male, he must agree to continue adequate contraception until 90 days after IP Dose 2
- •The participant can provide consent to participate in and having signed an ICF.
- •The participant is able and willing to complete all the scheduled study procedures during the whole study follow-up period (approximately 13 months).
排除标准
- •Exclusion criteria for Phase I
- •Participants meeting any of the following criteria will be excluded from Phase I of the study:
- •The participant has history of anaphylaxis to any allergen.
- •The participant has history of seizure disorder, encephalopathy or psychosis.
- •The female participant is pregnant (positive urine pregnancy test), lactating, or plans to become pregnant during the 3 months of enrollment.
- •The participant has a positive test result for HIV or hepatitis B and C.
- •The participant has a positive test results of IgG antibodies against SARS CoV 2 from RCT.
- •The participant has a positive test result of real-time quantitative PCR screening of nasopharyngeal swab/sputum for SARS-CoV-
- •The participant has a laboratory (hematological and biochemistry) examination that is out of normal range, or greater than a Grade 1 abnormality and clinically significant as assessed by the investigator including test results for: CBC, PT, PTT, ALT, AST, ALP, T Bil, Cr, lipase, and blood glucose;
- •- Transient mild laboratory abnormalities may be rescreened once, and the participant will be excluded if the laboratory repeat test is abnormal as per local laboratory normal values and the investigator's assessment.
- •The participant presents with any acute febrile disease (oral temperature ≥38.0°C) or active infectious disease.
- •The participant has a medical history of SARS-CoV-
- •The participant has unstable concomitant underlying conditions.
- •- Note: Stable condition defined as: The participant is appropriately managed on consistent disease management, for example participants with well controlled hypertension, adult-onset diabetes, Benign Prostate Hypertrophy (BPH) or hypothyroid disease will be eligible for enrollment. The treatment regimen should be stable for at least 3 months prior to entering the study. Once IP treatment has started, must be willing to maintain all aspects of the treatment regimen and forgo any elective changes in medication or management. Emergency changes in medication or management would be captured as an adverse event.
- •The participant has a history of Guillain-Barre Syndrome or degenerative neurological disorders; a history of autoimmune, inflammatory disease or potential immune-mediated medical conditions (PIMMCs), or any condition that may put the participant at increased risk of safety events
- •The participant has serious cardiovascular diseases, such as arrhythmia, conduction block, history of myocardial infarction, severe hypertension not controlled with medication.
- •The participant has a serious chronic disease such as asthma, diabetes, or thyroid disease.
- •The participant has immunodeficiency, asplenia, or functional asplenia.
- •The participant has a platelet disorder or other bleeding disorder that may cause contraindication for IM injection.
- •The participant has chronic obstructive pulmonary disease, current smoker or vaper.
- •The participant has a history or diagnosis of coagulopathies.
- •The participant has received immunosuppressive medication, cytotoxic therapy, or corticosteroids (excluding corticosteroid spray for allergic rhinitis, surface corticosteroid therapy for acute non-complicated dermatitis) in the last 6 months.
- •The participant received the blood products in last 4 months.
- •The participant has received other investigational drugs within 1 month before Day 0, or planned use during the study period.
- •The participant had prior administration of any live attenuated vaccine within 1 month before Day
- •The participant had prior administration of a subunit or inactivated non SARS CoV 2 vaccine within 2 weeks before Day
- •The participant had prior administration of any other vaccine considered (or being considered) to be protective against SARS-CoV-2 any time before Day
- •The participant had prior participation in other studies involving study intervention containing lipid nanoparticles.
- •The participant has any condition that, in the opinion of the investigator, may interfere with the participant's compliance, evaluation of study objectives, or informed consent process (i.e. medical, psychological, social or other conditions).
- •The participant is at high risk of acquiring SARS-CoV-2 infection due to their surroundings, contacts or circumstances. Explicitly exclude healthcare and essential workers/at risk population.
- •Exclusion criteria for Phase II
- •Participants meeting any of the following criteria will be excluded from Phase II part of the study:
- •The participant has history of anaphylaxis to any allergen.
- •The female participant is pregnant (positive urine pregnancy test), lactating, or plans to become pregnant during the next 3 months.
- •The participant has any acute febrile disease (oral temperature ≥38.0°C [100.4ºF]) or active infectious disease on the day of IP administration (participants may be re scheduled).
- •The participant has a medical history of SARS-CoV-
- •The participant has a history of immunodeficiency, asplenia, or functional asplenia.
- •The participant has received immunosuppressive medication, cytotoxic therapy, inhaled corticosteroids (excluding corticosteroid spray for allergic rhinitis, surface corticosteroid therapy for acute non-complicated dermatitis) in the last 6 months.
- •The participant has received other investigational drugs within 1 month before first dose administration or planned use during the study period.
- •The participant has received any live attenuated vaccine within 1 month before first dose administration or any inactivated vaccine within 2 weeks before first dose administration.
- •The participant has received prior administration of any other vaccine considered (or being considered) to protect against SARS-CoV-2 any time before study onset.
- •The participant has a history of any medical conditions that place them at higher risk for severe illness due to SARS-CoV-2 including but not limited to asthma, chronic kidney disease being treated with dialysis, chronic lung disease, diabetes, hemoglobin disorders, immunocompromised, liver disease, serious heart conditions, or severe obesity.
- •The participant has any condition that in the opinion of the investigators may interfere with the participants' compliance, evaluation of study objectives, or informed consent process (i.e., medical, psychological, social or other conditions).
研究组 & 干预措施
Placebo
Placebo injection. 12 subjects receiving placebo
干预措施: Covigenix VAX-001 placebo (Biological)
Active Covigenix VAX-001
Dose-ranging, 2 dose levels. 24 subjects receiving active i.m. vaccine
干预措施: Covigenix VAX-001 (Biological)
结局指标
主要结局
Safety of a 2-dose regimen of VAX-001 when doses are given 14 days apart
时间窗: Day 0 - 42
Frequency and Grade (mild, moderate, severe, potentially life-threatening; Gr. 1-4, respectively) of solicited injection site and systemic adverse events and unsolicited systemic adverse events
Mean change from baseline in safety laboratory measures
时间窗: Day 0 - 42
Adverse hematology /clinical chemistry parameter changes (mild, moderate, severe, or life-threatening; Gr. 1-4, respectively)
Frequency of treatment-emergent Serious Adverse Events (SAE) throughout the study and up to 12 months post-second dose immunization (Day 379).
时间窗: Day 0 - 379
Frequency of serious AEs
次要结局
- Persistence of IgG antibody titers as measured by ELISA and neutralizing antibody titers measured by pseudo-virion neutralization assay, six months after the second vaccine dose(Up to Day 379)
- Percent seroconversion defined as a 4-fold or greater increase in IgG titers after one or two doses as measured by IgG ELISA(Up to Day 379)
- Percent seroconversion defined as a 4-fold or greater increase in IgG titers after one or two doses as measured by pseudo-viral neutralization assay.(up to Day 379)
- Geometric mean neutralizing antibody titers against pseudo-virion after one and two doses(Up to Day 379)