A Phase I Open-Label, Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of an Ebola Sudan Chimpanzee Adenovirus Vector Vaccine, VRC-EBOADC086-00-VP (cAd3-EBO S), in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration
研究概览
简要总结
RV 508 was a Phase I, open-label, dose-escalation study to examine the safety, tolerability and immunogenicity of an investigational Ebola vaccine in healthy adults. VRC-EBOADC086-00-VP, a chimpanzee adenovirus serotype 3 vector-based Ebola vaccine, encodes wild type (WT) glycoprotein (GP) from the Sudan strain of Ebolavirus and is administered intramuscularly (IM).
详细描述
A total of 40 participants were evenly split, with 20 in each of the two dosage groups to receive the investigational cAd3-EBO S vaccine at a dose of either 1x10^10 particle units (PU) (Group 1) or 1x10^11 PU (Group 2). The dose escalation plan included daily review of any new safety data by a study clinician, regular review of safety data by the protocol team and a staged enrollment plan with required interim safety reviews. The study began with enrollment of 3 participants into Group 1 (1x10^10 PU) at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated participants, an interim safety review occurred before enrollment of additional participants into the group. No safety issues were identified; therefore, an additional 17 participants were enrolled to complete Group 1. When there was a minimum of seven days of follow-up safety data from the last enrolled participant in Group 1, an interim safety review occurred. No safety issues were identified, and enrollment of participants into the next dose level (Group 2) began with the enrollment of 3 participants at a rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated participants in Group 2 (1x10^11 PU), an interim safety review occurred before the enrollment of additional participants into Group 2. No safety issues were identified, and an additional 17 participants were enrolled to complete Group 2. Participants were followed for approximately 48 weeks.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to 50 years old.
- •Available for clinical follow-up through Week 48 after enrollment.
- •Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- •Able and willing to provide fingerprints and have their photographs taken including injection site photographs.
- •Must allow home visits
- •Must complete an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions at least once in 3 attempts.
- •Able to read (English or Luganda) and willing to complete the informed consent process.
- •In good general health without clinically significant medical history.
- •Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ≤ 40 within the 56 days prior to enrollment.
- •Laboratory Criteria within 56 days prior to enrollment:
- •Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.
- •White blood cells (WBC) = 2,500-12,000 cells/mm^
- •Total lymphocyte count ≥ 800 cells/mm^
- •Platelets = 125,000 - 400,000/mm^
- •Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal.
- •Serum creatinine ≤ 1 x upper limit of normal.
- •HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic test.
- •Female-Specific Criteria:
- •Negative β-HCG (human chorionic gonadotropin) pregnancy test; serum β-HCG at screening and urine β-HCG at enrollment if woman is of reproductive potential.
- •Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after study vaccination if assessed to be of reproductive potential.
排除标准
- •Volunteer has received any of the following substances:
- •Investigational Ebola or Marburg vaccine in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine.
- •Chronic use of immunomodulators and systemic glucocorticoids in daily doses of glucocorticoid equivalence > 20 mg of prednisolone, for periods exceeding 10 days. Non-steroidal anti-inflammatory drugs [NSAIDS] are permitted. Participants that have used less than the stated glucocorticoid dose may still be excluded at the Investigator's discretion.
- •Blood products within 112 days (16 weeks) prior to enrollment.
- •Investigational research agents within 28 days (4 weeks) prior to enrollment.
- •Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.
- •Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.
- •Current anti-tuberculosis prophylaxis or therapy.
- •Female-specific criteria:
- •Woman who is pregnant, breast-feeding or planning to become pregnant during the first 24 weeks after study vaccine administration.
- •Volunteer has a history of any of the following clinically significant conditions:
- •Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
- •Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or streptomycin.
- •Clinically significant autoimmune disease or immunodeficiency.
- •Asthma that is not well controlled.
- •Positive result on a rapid plasma reagin (RPR) test.
- •Diabetes mellitus (type I or II).
- •Thyroid disease that is not well controlled.
- •A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.
- •Idiopathic urticaria within the last 1 year.
- •Hypertension that is not well controlled.
- •Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
- •A malignancy that is active, currently being treated, or not surgically cured.
- •Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.
- •Asplenia or functional asplenia.
- •Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within five years prior to enrollment, history of a suicide plan or attempt.
- •Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
结局指标
主要结局
Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration
时间窗: 7 days after study product administration
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: Through 48 weeks after study product administration
SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 48. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs)
时间窗: Through 28 days after study product administration
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the study product administration through the visit scheduled for 28 days after study product administration. At other time periods greater than 28 days after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration
时间窗: 7 days after study product administration
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. The majority of the reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007. The Division of AIDS AE Grading Table, Corrected Version 2.1 was used to grade reported events of joint pain (arthralgia).
Total Number of Participants Reporting Any Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration
时间窗: 7 days after study product administration
Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after the study product administration.
Number of Participants With Abnormal Laboratory Measures of Safety
时间窗: Through 48 weeks after study product administration
Any abnormal laboratory results recorded as unsolicited AEs are summarized. Labs included hematology (hemoglobin, hemoglobin change from baseline, hematocrit percent, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC) and lymphocyte counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC) with total lymphocyte count results were collected at screening (≤ 56 days before enrollment), Day 0 prior to study product administration (baseline), Day 3, and Weeks 2, 4, 8 and 24. Creatinine and ALT results were collected at screening, Day 0, Day 3 and Weeks 2, 4 and 8. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials, modified from FDA Guidance-September 2007 were used. Neutrophil results were not collected in the study database but were captured in the subject's laboratory results documentation.
次要结局
- Baseline-subtracted Geometric Mean Titers of cAd3-EBO S Antibodies After the cAd3-EBO S Vaccine Administration(Through 28 days after study product administration)
- Percentage of Participants With Positive Ebola-specific T Cell Responses After the cAd3-EBO S Vaccine Administration(Through 28 days after study product administration)
- Geometric Mean Titers of Antibodies to the Recombinant Chimpanzee Adenovirus Serotype 3 (cAd3) Vector at 28 Days After the cAd3-EBO S Vaccine Administration(Through 28 days after study product administration)
- Percentage of Participants With a Positive Ebola-Specific Antibody Response After the cAd3-EBO S Vaccine Administration(Through 28 days after study product administration)
- Magnitude of T Cell Response as a Percentage of EBO S-specific T Cell Subset After the cAd3-EBO S Vaccine Administration(Through 28 days after study product administration)