A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Immunogenicity and Efficacy of A Respiratory Syncytial Virus Vaccine (RSVpreF) in A Virus Challenge Model in Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Hvivo
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- Area Under the Viral Load-time Curve (VL-AUC) of RSV
研究概览
简要总结
In this randomised, placebo-controlled, double-blind Phase 2a study, healthy male and female participants 18-50 years of age will be given an investigational RSV vaccine (RSVpreF) and challenged with RSV one month later. The purpose of this research study is to assess the safety, immunogenicity and efficacy of RSVpreF using a human viral challenge model.
详细描述
Respiratory Syncytial Virus (RSV) is a common virus that affects all human age groups and can cause a range of respiratory disease such as bronchitis and lower respiratory infections. These serious illnesses affect infants and adults who are older especially if they are over 65, have chronic heart or lung disease or have a weakened immune system. Vaccination against RSV has the potential to be a highly beneficial and effective approach to reduce RSV disease in older adults and pediatric populations, however there is no current vaccine approved for the prevention of RSV infections.
RSVpreF is being developed to prevent RSV-associated moderate to severe lower respiratory tract disease in adults 60 years of age and in infants by active immunization of pregnant women.
This study is an exploratory proof-of-concept to assess the safety, immunogenicity and efficacy of RSVpreF using a human challenge model. The RSV challenge model is developed to help understanding the RSV disease and assess new vaccines by testing them in participants deliberately infected with the virus.
In this study, approximately 62 (up to 72) participants will be vaccinated with the investigational RSVpreF to account for withdrawals between vaccination and challenge. Participants will be randomised 1:1 to receive RSVpreF or placebo.
The study will consist of a vaccination phase, quarantine phase and a follow-up phase.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double blinded, placebo-controlled study
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
- •An informed consent document signed and dated by the participant and the Investigator.
- •Aged between 18 and 50 years.
- •In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety.
- •A documented medical history prior to enrolment.
- •The following criteria are applicable to female participants participating in the study.
- •Females of childbearing potential must have a negative pregnancy test prior to enrolment.
- •Females of non-childbearing potential:
- •Post-menopausal females; defined as having a history of amenorrhea for >12 months with no alternative medical cause, and /or by FSH level >40mIU/mL, confirmed by laboratory.
- •Documented status as being surgically sterile (e.g. tubal ligation, hysterectomy, bilateral salpingectomy and bilateral oophorectomy).
- •The following criteria apply to female and male participants:
- •Female participants of childbearing potential must use one form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to the first study visit. The contraception use must continue until 28 days after the date of viral challenge/last dosing with IMP (whichever occurs last).
- •Male participants must agree to the contraceptive requirements below at entry to quarantine and continuing until 28 days after the date of Viral challenge / last dosing with IMP (whichever occurs last): a. Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent exposure of any partner (male and female) to the IMP. b. Male sterilisation with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate (please note that the use of condom with spermicide will still be required to prevent partner exposure). This applies only to males participating in the study. c. In addition, for female partners of child bearing potential, that partner must use another form of contraception such as one of the highly effective methods mentioned above for female participants.
- •In addition to the contraceptive requirements above, male participants must agree not to donate sperm following discharge from quarantine until 28 days after the date of Viral Challenge/last dosing with IMP (whichever occurs last).
- •True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
- •Sero-suitable to the challenge virus.
排除标准
- •History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to the first study visit.
- •a) Any history or evidence of any other clinically significant or currently active systemic comorbidities including psychiatric disorders (includes participants with a history of depression and/or anxiety).
- •b) And/or other major disease that, in the opinion of the Investigator, may put the participant at undue risk, or interfere with a participant completing the study and necessary investigations (e.g autoimmune disease or immunodeficiency).
- •Participants who have smoked ≥ 10 pack years at any time [10 pack years is equivalent to one pack of 20 cigarettes a day for 10 years].
- •A total body weight ≤ 50 kg and Body Mass Index (BMI) ≤18 kg/m2 and ≥30kg/m
- •Females who:
- •Are breastfeeding, or
- •Have been pregnant within 6 months prior to the study.
- •History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug or vaccine, including hypersensitivity to any of the constituents of the study vaccine, as assessed by the PI.
- •Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
- •a) Any significant abnormality altering the anatomy of the nose in a substantial way b) Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months c) Any nasal or sinus surgery within 3 months
- •a) Evidence of vaccinations with licensed live attenuated vaccines within the 4 weeks prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first). Evidence of vaccinations with licensed vaccines which are not live attenuated within the 2 weeks prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first).
- •b) Intention to receive any vaccination(s) before at least 28 days after the viral challenge (NB. No travel restrictions will apply after the Day 28 Follow-up visit).
- •Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 2 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first) or planned during the 2 months after the viral challenge.
- •a) Receipt of any investigational drug within 3 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first).
- •b) Previous vaccination with any licensed or investigational RSV vaccine before enrolment into the study. c) Receipt of three or more investigational drugs within the previous 12 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first).
- •d) Prior inoculation with a virus from the same virus-family as the challenge virus.
- •e) Prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
- •f) Receipt of treatment with immunosuppressive therapy.
- •a) Confirmed positive test for drugs of abuse and cotinine on first study visit. One repeat test allowed at PI discretion.
- •b) History or presence of alcohol addiction, or excessive use of alcohol
- •A forced expiratory volume in 1 second (FEV1) < 80%.
- •Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test.
- •Those employed or immediate relatives of those employed at hVIVO, Pfizer or any vendor.
- •Any other finding that, in the opinion of the Investigator, deems the Participant unsuitable for the study.
结局指标
主要结局
Area Under the Viral Load-time Curve (VL-AUC) of RSV
时间窗: Day 2 to Day 12
The VL-AUC of RSV determined by qRT-PCR from nasal wash samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine.
Sum Total Symptoms Diary Card Score (TSS)
时间窗: Day 1 to Day 12
The sum total symptoms score is the sum of all scores from the first assessment on Day 1 to the first assessment on Day 12 (34 assessments). Symptom scores were collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine using a participant self-reportable 13-symptoms card. Clinical symptoms include runny nose, stuffy nose, sneezing, sore throat, earache, malaise/tiredness, headache, muscle or joint ache, chilliness/feverishness, cough, chest tightness, shortness of breath, and wheeze. Participants scored symptoms from 0 (no symptoms) - 3 (severe). Shortness of breath and wheeze had an additional scoring option of grade 4. For each assessment, an individual total symptom score was derived as the total of the scores given to the 13 symptoms on that symptom score card. Individual total symptom scores ranged from 0 (if all symptoms graded 0) to 41 (if all symptoms graded 3 and shortness of breath and wheeze graded 4).
Number of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection
时间窗: Day 2 to Day 12
RT-PCR-confirmed symptomatic RSV infection defined as: \- Two detectable qRT-PCR reported on 2 or more consecutive days (any two detectable (≥LLOD) qRT-PCR measurements reported over 4 consecutive scheduled timepoints). and \- Either one or more positive clinical symptoms from different categories in the symptom scoring system or one Grade 2 symptom from any category
次要结局
- VL-AUC Determined by Quantitative Viral Culture(Day 2 to Day 12)
- Number of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days(Day 2 to Day 12)
- Number of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days(Day 2 to Day 12)
- Number of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge(Day 0 to Day 28)
- Use of Concomitant Medication(From Vaccination (Day -28) until Viral Challenge (Day 0), and From Viral Challenge (Day 0) until Day 28)
- Duration of Quantifiable qRT-PCR Measurements(Day 2 to Day 12)
- Peak Symptoms Diary Card Score(Day 1 to Day 12)
- Number of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection(Day 2 to Day 12)
- Peak Viral Load of RSV by qRT-PCR(Day 2 to Day 12)
- Number of Participants With Culture Lab-confirmed Reduction of Symptomatic RSV Infection(Day 2 to Day 12)
- Peak Viral Load of RSV by Viral Culture(Day 2 to Day 12)
- Duration of Quantitative Viral Culture Measurements(Day 2 to Day 12)
- Area Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)(Day 1 to Day 12)
- Peak Daily Symptom Score(Day 1 to Day 12)
- Total Mucus Weight(Day 1 to Day 12)
- Number of Systemic Events Within 7 Days After Vaccination(7 days post vaccination)
- Percentage Number of Participants With Grade 2 or Higher Symptoms(Day 1 to Day 12)
- Number of Solicited Local Reactions Within 7 Days After Vaccination(7 days post vaccination)
- Occurrence of Medically Attended AEs(Through study completion, an average of 6 months)
- Occurrence of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period.(Day -2 to Day12)
- Number of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements(Day 2 to Day 12)
- Total Tissue Number(Day 1 to Day 12)
- Number of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination(30 days)
- Occurrence of SAEs(Through study completion, an average of 6 months)