A Phase 1 Randomized, Single-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety and Immunogenicity of rVSV∆G-MARV-GP [Angola] (PHV01, MARV GP Vaccine) in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Unsolicited AEs
研究概览
简要总结
This is a Phase 1 randomized, single-blind, placebo-controlled, ascending dose study to evaluate the safety and immunogenicity of rVSV∆G-MARV-GP [Angola] (PHV01, Marburg Virus glycoprotein [MARV GP] Vaccine) in healthy adults. PHV01 is a live, attenuated rVSV vaccine expressing the MARV GP. The main questions it aims to answer are:
- Which dose of PHV01 is safe to administer to, and well-tolerated by healthy adult subjects?
- What is the immunologic response (Marburg-specific Immunoglobulin G (IgG) ELISA antibody and neutralizing antibodies) to each dose level?
Participants will receive 1 intramuscular injection of PHV01 or placebo on Day 1 and will be followed for 181 days.
详细描述
Participants will be randomly assigned to vaccine or placebo in four dose cohorts, starting with evaluation of safety using a sentinel group at each dose level, followed by dosing of the rest of the group in the next cohort. That next cohort will also dose the sentinel group with the next higher dose.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Single-blind
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or non-pregnant, non-lactating females, age 18-60 years
- •Given written informed consent
- •No clinically significant health problems
- •Negative test for SARS-CoV-2
- •Agree to avoid conception through Day 29
- •Agree to minimize blood and body fluid exposures to others after vaccination through Day 29
- •Agree to avoid exposure to immunocompromised persons after vaccination through Day 29
排除标准
- •Prior infection with Marburg virus, related filovirus, or Ebola virus
- •Prior infection with vesicular stomatitis virus (VSV)
- •Received any VSV-vectored vaccine
- •BMI of ≥ 35
- •Household contact who is immunodeficient, or on immunosuppressive medication
- •Hepatitis B, hepatitis C, HIV-1, HIV-2, history of long COVID, diabetes, atopic dermatitis (eczema), chronic inflammatory disease, autoimmune or autoinflammatory disorder, malignancy, chronic or active neurologic disorder
- •History of severe reactions to any vaccine or history of severe allergies
- •Receipt of investigational product up to 30 days prior to randomization
- •Receipt of licensed or authorized non-live vaccines within 14 days of planned study immunization (30 days for live vaccines).
- •Known allergy to components of PHV01
- •Injection sites obscured by tattoos or physical condition
- •Significant psychiatric or medical condition or laboratory abnormality on screening
- •History of Guillain Barre Syndrome or any chronic or acute neurological disorder
- •Alcohol or illicit drug abuse within past 5 years
- •Pregnant or lactating female
- •Administration of blood or IgG within 60 days preceding study
- •Administration of systemic chronic immunosuppressants (defined as more than 14 days) or other immune modifying drugs within 6 months of study entry
- •History of blood donation within 60 days of study
- •Unwilling to undergo diagnostic evaluation of rash (skin biopsy, if indicated) or joint symptoms (arthrocentesis if indicated by joint effusion), in both cases if acceptable to subject
- •Elective surgery planned during the study period
研究组 & 干预措施
Group A, Low Dose PHV01
Group A (10 subjects) PHV01 @ 10^5 pfu/dose given once
干预措施: PHV01 (Biological)
Group B, Medium Dose PHV01
Group B (10 subjects) PHV01 @ 10^6 pfu/dose given once
干预措施: PHV01 (Biological)
Group C, Hjigh Dose PHV01
Group C (10 subjects) PHV01 @ 10^7 pfu/dose given once
干预措施: PHV01 (Biological)
Group D, Placebo
Group D (6 subjects) Placebo given once
干预措施: Placebo (Biological)
结局指标
主要结局
Unsolicited AEs
时间窗: Study Days 1-29
Incidence and severity of unsolicited AEs
Immunogenicity, Antibodies (Ab)
时间窗: Injection through 28 days
Geometric mean titers (GMT) of Marburg GP protein-specific IgG antibody as measured by enzyme-linked immunosorbent assay (ELISA) on days 1 and 29
Immunogenicity, Neutralizing antibodies (NEUT)
时间窗: Injection through 28 days
PsVNT50 and PsVNT80 MARV GP-specific neutralizing antibodies titers
Solicited Adverse Events (AEs)
时间窗: Study Days 1-15
Incidence and severity of solicited injection site \[(arm pain, local tenderness, erythema (redness), and induration (swelling/firmness)\] and systemic AEs
Other AEs
时间窗: Study Days 1-181
Incidence and severity of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs)
次要结局
未报告次要终点