Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: RSVPreF
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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. 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/m2. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSVPreF<br>A single intramuscular injection at a dose of 120 mcg reconstituted with sterile water for an 0.5 mL injection volume | Biological: RSVPreF<br>* A single dose of 120 mcg RSVpreF for intramuscular injection<br>|
| Placebo Comparator: Placebo<br>A single intramuscular injection of Placebo to match active vaccine | Other: Placebo<br>* A single Placebo dose for intramuscular injection to match experimental vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the viral load-time curve (VL-AUC) of RSV | The VL-AUC of RSV determined by qRT-PCR from nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine. | Day 2 to Day 12 | 
| RT-PCR-confirmed symptomatic RSV infection | RT-PCR-confirmed symptomatic RSV infection defined as: Two detectable qRT-PCR reported on 2 or more consecutive days and Either one or more positive clinical symptoms from different categories in the symptom scoring system or one Grade 2 symptom from any category | Day 2 to Day 12 | 
| Sum total symptoms diary card score (TSS) | TSS is measured by graded symptom scoring system collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine | Day 1 to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RT-PCR confirmed incidence of symptomatic infection | RT-PCR confirmed RSV infection defined as Two quantifiable PCR measures reported on 2 or more consecutive days, and Either one or more positive clinical symptoms from different categories in the symptom scoring system or one Grade 2 symptom from any category | Day 2 to Day 12 | 
| Culture lab-confirmed reduction of symptomatic RSV infection | Culture lab-confirmed symptomatic RSV infection defined as: One quantifiable viral culture and Either one or more positive clinical symptoms from different categories in the symptom scoring system or one Grade 2 symptom from any category | Day 2 to Day 12 | 
| Peak viral load of RSV by qRT-PCR | Reduction in Peak viral load of RSV determined by quantifiable qRT-PCR from nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine. | Day 2 to Day 12 | 
| Peak viral load of RSV by viral culture | Peak viral load of RSV determined by quantifiable viral culture from nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine. | Day 2 to Day 12 | 
| Duration of quantifiable qRT-PCR measurements | Duration (time in hours) of quantifiable qRT-PCR measurements from nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine. | Day 2 to Day 12 | 
| Duration of quantitative viral culture measurements | Duration (time in hours) of quantitative viral culture measurements from nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine. | Day 2 to Day 12 | 
| VL-AUC determined by quantitative viral culture | VL-AUC of RSV as determined by quantitative viral culture on nasal samples starting two days post-viral challenge (Day +2) up to discharge from quarantine | Day 2 to Day 12 | 
| Area under the curve over time of total clinical symptoms (TSS-AUC) | TSS-AUC as measured by graded symptom scoring system collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine. | Day 1 to Day 12 | 
| Peak symptoms diary card score | Peak TSS as measured by graded symptom scoring system collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine. | Day 1 to Day 12 | 
| Peak daily symptom score | Individual maximum daily sum of symptom score starting one day post-viral challenge (Day +1) up to the end of quarantine | Day 1 to Day 12 | 
| Percentage number of participants with Grade 2 or higher symptoms | Number (%) of participants with Grade 2 or higher symptoms | Day 1 to Day 12 | 
| Occurrence of at least two positive quantifiable qRT-PCR measurements on 2 or more consecutive days |  | Day 2 to Day 12 | 
| Occurrence of at least two positive detectable qRT-PCR measurements on 2 or more consecutive days |  | Day 2 to Day 12 | 
| Occurrence of at least one positive quantitative cell culture measurements on 2 or more consecutive days |  | Day 2 to Day 12 | 
| Total mucus weight | Total weight of mucus produced starting one day post-viral challenge (Day +1) up to discharge from quarantine. | Day 1 to Day 12 | 
| Total tissue number | Total number of tissues used by participants starting one day post-viral challenge (Day +1) up to discharge from quarantine. | Day 1 to Day 12 | 
| Number of solicited local reactions within 7 days after vaccination |  | 7 days | 
| Number of systemic events within 7 days after vaccination |  | 7 days | 
| Occurrence of unsolicited adverse events (AEs) post vaccination | Number of unsolicited adverse events (AEs) within 30 days after vaccination | 30 days | 
| Occurrence of medically attended AEs | Number of medically attended AEs from vaccination to study end | Through study completion, an average of 6 months | 
| Occurrence of SAEs | Number of SAEs from vaccination to study end | Through study completion, an average of 6 months | 
| Occurrence of unsolicited AEs related to viral challenge | Number of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day +28 follow up. | Day 0 to Day 28 | 
| Occurrence of haematological and biochemical laboratory abnormalities during the quarantine period. | Number of Safety Laboratory Assessment Abnormalities reported as AEs | Day -2 to Day12 | 
| Use of concomitant medication |  | within 30 days post viral challenge |