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
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- Hvivo
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Area Under the Viral Load-time Curve (VL-AUC) of RSV
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Area Under the Viral Load-time Curve (VL-AUC) of RSV
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Secondary Outcomes
- 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)