CClinicalTrials.gg
CompletedNCT04785612Updated Aug 7, 2024Results posted

Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults

A Phase 2 interventional study of RSVPreF and Placebo in Respiratory Syncytial Virus Infections, sponsored by Hvivo. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-07.

Sponsored by Hvivo · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
70
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Respiratory Syncytial Virus Infections
03

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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.

    1. Females of childbearing potential must have a negative pregnancy test prior to enrolment.
    2. Females of non-childbearing potential:

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    1. 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.
    2. 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:

    1. 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).
    2. 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).

    3. 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

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:

    1. Are breastfeeding, or
    2. 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.
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
70 participants (actual)

Study arms

  • Experimental
    RSVPreF

    A single intramuscular injection at a dose of 120 mcg reconstituted with sterile water for an 0.5 mL injection volume

    Biological: RSVPreF

  • Placebo comparator
    Placebo

    A single intramuscular injection of Placebo to match active vaccine

    Other: Placebo

Interventions

  • BiologicalRSVPreF

    A single dose of 120 mcg RSVpreF for intramuscular injection

  • OtherPlacebo

    A single Placebo dose for intramuscular injection to match experimental vaccine

05

What researchers measure

Primary outcomes

  1. Area Under the Viral Load-time Curve (VL-AUC) of RSV

    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.

    Time frame: Day 2 to Day 12

  2. Number of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection

    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

    Time frame: Day 2 to Day 12

  3. Sum Total Symptoms Diary Card Score (TSS)

    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).

    Time frame: Day 1 to Day 12

Secondary outcomes

  1. Number of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection

    RT-PCR confirmed RSV infection defined as * Two quantifiable PCR measures reported on 2 or more consecutive days (any two quantifiable (≥LLOQ) 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

    Time frame: Day 2 to Day 12

  2. Number of Participants With 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

    Time frame: Day 2 to Day 12

  3. 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.

    Time frame: Day 2 to Day 12

  4. 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.

    Time frame: Day 2 to Day 12

  5. 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.

    Time frame: Day 2 to Day 12

  6. 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.

    Time frame: Day 2 to Day 12

  7. 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

    Time frame: Day 2 to Day 12

  8. Area Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)

    Data presented is hours \* score. TSS-AUC (trapezium rule) as measured by graded symptom scoring system collected 3 times daily starting Day +1 up to Day 12am using a participant self-reportable 13-symptoms card, the max number of diary cards included in the AUC calculation is 34, the maximum time period is 264hrs. Clinical symptoms included 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 symptom from 0 (no symptoms) - 3(severe). Shortness of breath and wheeze had an additional scoring option of grade 4. Dairy card 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). The range of TSS AUC scores are between 0 and 10,824 hours\*score (maximum of 264x41).

    Time frame: Day 1 to Day 12

  9. Peak Symptoms Diary Card Score

    Peak TSS for each participant is defined as the diary card total with the worst score (highest). The symptom scoring system was 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).

    Time frame: Day 1 to Day 12

  10. Peak Daily Symptom Score

    Peak daily symptom score was derived, for each day from Day 1 to Day 12, as the maximum of the 3 total symptoms scores on that day, providing 11 scores each. The symptoms 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).

    Time frame: Day 1 to Day 12

  11. Percentage Number of Participants With Grade 2 or Higher Symptoms

    Number (%) of participants with Grade 2 or higher symptoms (on any occasion from Day 1 to Day 12)

    Time frame: Day 1 to Day 12

  12. Number of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days

    The number of participants with at least two quantifiable positive (≥LLOQ) qRT-PCR nasal sample measurements across 4 consecutive visits

    Time frame: Day 2 to Day 12

  13. Number of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days

    The proportion of participants with at least two positive detectable qRT-PCR nasal sample measurements across 4 consecutive visits

    Time frame: Day 2 to Day 12

  14. Number of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements

    The proportion of participants with at least one quantifiable positive (≥LLOQ) nasal sample viral culture starting two days post-viral challenge (Day+2) up to discharge from quarantine. Viral culture is only done for samples where qRT-PCR is positive (detectable), when the qRT-PCR is negative the viral culture is assumed to be 0 for any endpoint derivations.

    Time frame: Day 2 to Day 12

  15. Total Mucus Weight

    Total weight of mucus produced starting one day post-viral challenge (Day +1) up to discharge from quarantine. The mean sum of all mucus produced from Day 1 to Day 12 is reported in data table.

    Time frame: Day 1 to Day 12

  16. Total Tissue Number

    Total number of tissues used by participants starting one day post-viral challenge (Day +1) up to discharge from quarantine.

    Time frame: Day 1 to Day 12

  17. Number of Solicited Local Reactions Within 7 Days After Vaccination

    Local reactions include pain at injection site, redness and swelling

    Time frame: 7 days post vaccination

  18. Number of Systemic Events Within 7 Days After Vaccination

    Systemic reactions included fever, fatigue, headache, vomiting, nausea, diarrhea, muscle pain, and joint pain. Each of these items was collected on a four-point scale including, none, mild, moderate, and severe.

    Time frame: 7 days post vaccination

  19. Number of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination

    Number of participants with at least one unsolicited adverse events (AEs) within 30 days after vaccination. Unsolicited AEs were all AEs for which participants were not specifically questioned in the participant diary.

    Time frame: 30 days

  20. Occurrence of Medically Attended AEs

    Number of medically attended AEs from vaccination to study end

    Time frame: Through study completion, an average of 6 months

  21. Occurrence of SAEs

    Number of SAEs from vaccination to study end

    Time frame: Through study completion, an average of 6 months

  22. Number of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge

    Number of participants with at least one unsolicited AE within 30 days post-viral challenge (Day 0) up to Day +28 follow up. Unsolicited AEs were all AEs for which participants were not specifically questioned in the participant diary.

    Time frame: Day 0 to Day 28

  23. Occurrence of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period.

    Number of hematological and biochemical laboratory assessment Abnormalities reported as AEs during the quarantine period.

    Time frame: Day -2 to Day12

  24. Use of Concomitant Medication

    Concomitant medications (prescription and over the counter drugs and supplements that a study participant had taken alongside the study vaccination) were recorded for the period following vaccination (up to viral challenge) and from viral challenge until Day 28..

    Time frame: From Vaccination (Day -28) until Viral Challenge (Day 0), and From Viral Challenge (Day 0) until Day 28

06

Results

Posted Aug 7, 2024

Participant flow

70 participants were to be enrolled and vaccinated with the study vaccine, with 62 participants challenged with the study virus.

Participant flow — Overall Study
MilestoneRSVPreFPlacebo
Started3535
Completed3131
Not completed44

Outcome measures

PrimaryArea Under the Viral Load-time Curve (VL-AUC) of RSV

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.

Time frame:
Day 2 to Day 12
Reported as:
Median · h*log10 PFU/mL
Area Under the Viral Load-time Curve (VL-AUC) of RSV
h*log10 PFU/mLRSVPreFPlacebo
Area Under the Viral Load-time Curve (VL-AUC) of RSV0.00 (0.0 to 19.02)96.65 (0.0 to 675.32)
PrimaryNumber of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection

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

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection
ParticipantsRSVPreFPlacebo
Number of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection215
PrimarySum Total Symptoms Diary Card Score (TSS)

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).

Time frame:
Day 1 to Day 12
Reported as:
Geometric mean · score on a scale
Sum Total Symptoms Diary Card Score (TSS)
score on a scaleRSVPreFPlacebo
Sum Total Symptoms Diary Card Score (TSS)2.1 ± 199.828.9 ± 120.2
SecondaryNumber of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection

RT-PCR confirmed RSV infection defined as * Two quantifiable PCR measures reported on 2 or more consecutive days (any two quantifiable (≥LLOQ) 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

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection
ParticipantsRSVPreFPlacebo
Number of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection013
SecondaryNumber of Participants With 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

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With Culture Lab-confirmed Reduction of Symptomatic RSV Infection
ParticipantsRSVPreFPlacebo
Number of Participants With Culture Lab-confirmed Reduction of Symptomatic RSV Infection011
SecondaryPeak 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.

Time frame:
Day 2 to Day 12
Reported as:
Median · log 10 copies/mL
Peak Viral Load of RSV by qRT-PCR
log 10 copies/mLRSVPreFPlacebo
Peak Viral Load of RSV by qRT-PCR0.00 (0.0 to 3.1080)4.2 (0.0 to 6.9990)
SecondaryPeak 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.

Time frame:
Day 2 to Day 12
Reported as:
Mean · log 10 PFU/mL
Peak Viral Load of RSV by Viral Culture
log 10 PFU/mLRSVPreFPlacebo
Peak Viral Load of RSV by Viral Culture0.00 ± 0.001.921 ± 2.3837
SecondaryDuration 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.

Time frame:
Day 2 to Day 12
Reported as:
Median · hours
Duration of Quantifiable qRT-PCR Measurements
hoursRSVPreFPlacebo
Duration of Quantifiable qRT-PCR Measurements18.0 (11.8 to 54.4)131.6 (72.1 to NA)
SecondaryDuration 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.

Time frame:
Day 2 to Day 12
Reported as:
Median · hours
Duration of Quantitative Viral Culture Measurements
hoursRSVPreFPlacebo
Duration of Quantitative Viral Culture Measurements—83.1 (60.2 to 95.8)
SecondaryVL-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

Time frame:
Day 2 to Day 12
Reported as:
Mean · h*log10 PFU/mL
VL-AUC Determined by Quantitative Viral Culture
h*log10 PFU/mLRSVPreFPlacebo
VL-AUC Determined by Quantitative Viral Culture0.00 ± 0.0091.91 ± 127.883
SecondaryArea Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)

Data presented is hours \* score. TSS-AUC (trapezium rule) as measured by graded symptom scoring system collected 3 times daily starting Day +1 up to Day 12am using a participant self-reportable 13-symptoms card, the max number of diary cards included in the AUC calculation is 34, the maximum time period is 264hrs. Clinical symptoms included 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 symptom from 0 (no symptoms) - 3(severe). Shortness of breath and wheeze had an additional scoring option of grade 4. Dairy card 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). The range of TSS AUC scores are between 0 and 10,824 hours\*score (maximum of 264x41).

Time frame:
Day 1 to Day 12
Reported as:
Mean · hours * score on a scale
Area Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)
hours * score on a scaleRSVPreFPlacebo
Area Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)52.85 ± 105.250230.76 ± 277.988
SecondaryPeak Symptoms Diary Card Score

Peak TSS for each participant is defined as the diary card total with the worst score (highest). The symptom scoring system was 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).

Time frame:
Day 1 to Day 12
Reported as:
Mean · score on a scale
Peak Symptoms Diary Card Score
score on a scaleRSVPreFPlacebo
Peak Symptoms Diary Card Score1.3 ± 1.794.1 ± 3.92
SecondaryPeak Daily Symptom Score

Peak daily symptom score was derived, for each day from Day 1 to Day 12, as the maximum of the 3 total symptoms scores on that day, providing 11 scores each. The symptoms 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).

Time frame:
Day 1 to Day 12
Reported as:
Mean · score on a scale
Peak Daily Symptom Score
score on a scaleRSVPreFPlacebo
Day 10.6 ± 1.380.2 ± 0.56
Day 20.4 ± 0.760.3 ± 0.70
Day 30.3 ± 0.690.2 ± 0.50
Day 40.3 ± 0.731.1 ± 2.16
Day 50.5 ± 1.481.6 ± 2.78
Day 60.6 ± 1.122.2 ± 2.77
Day 70.4 ± 0.712.5 ± 3.04
Day 80.3 ± 0.582.5 ± 3.30
Day 90.3 ± 0.511.3 ± 1.59
Day 100.2 ± 0.550.7 ± 1.03
Day 110.2 ± 0.750.8 ± 1.51
Day 120.0 ± 0.180.5 ± 1.89
SecondaryPercentage Number of Participants With Grade 2 or Higher Symptoms

Number (%) of participants with Grade 2 or higher symptoms (on any occasion from Day 1 to Day 12)

Time frame:
Day 1 to Day 12
Reported as:
Count of participants · Participants
Percentage Number of Participants With Grade 2 or Higher Symptoms
ParticipantsRSVPreFPlacebo
Percentage Number of Participants With Grade 2 or Higher Symptoms516
SecondaryNumber of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days

The number of participants with at least two quantifiable positive (≥LLOQ) qRT-PCR nasal sample measurements across 4 consecutive visits

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days
ParticipantsRSVPreFPlacebo
Number of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days416
SecondaryNumber of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days

The proportion of participants with at least two positive detectable qRT-PCR nasal sample measurements across 4 consecutive visits

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days
ParticipantsRSVPreFPlacebo
Number of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days1023
SecondaryNumber of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements

The proportion of participants with at least one quantifiable positive (≥LLOQ) nasal sample viral culture starting two days post-viral challenge (Day+2) up to discharge from quarantine. Viral culture is only done for samples where qRT-PCR is positive (detectable), when the qRT-PCR is negative the viral culture is assumed to be 0 for any endpoint derivations.

Time frame:
Day 2 to Day 12
Reported as:
Count of participants · Participants
Number of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements
ParticipantsRSVPreFPlacebo
Number of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements013
SecondaryTotal Mucus Weight

Total weight of mucus produced starting one day post-viral challenge (Day +1) up to discharge from quarantine. The mean sum of all mucus produced from Day 1 to Day 12 is reported in data table.

Time frame:
Day 1 to Day 12
Reported as:
Mean · g
Total Mucus Weight
gRSVPreFPlacebo
Total Mucus Weight6.367 ± 9.824629.135 ± 36.2811
SecondaryTotal Tissue Number

Total number of tissues used by participants starting one day post-viral challenge (Day +1) up to discharge from quarantine.

Time frame:
Day 1 to Day 12
Reported as:
Mean · Tissues
Total Tissue Number
TissuesRSVPreFPlacebo
Total Tissue Number16.9 ± 22.3541.7 ± 44.80
SecondaryNumber of Solicited Local Reactions Within 7 Days After Vaccination

Local reactions include pain at injection site, redness and swelling

Time frame:
7 days post vaccination
Reported as:
Count of participants · Participants
Number of Solicited Local Reactions Within 7 Days After Vaccination
ParticipantsRSVPreFPlacebo
Number of Solicited Local Reactions Within 7 Days After Vaccination52
SecondaryNumber of Systemic Events Within 7 Days After Vaccination

Systemic reactions included fever, fatigue, headache, vomiting, nausea, diarrhea, muscle pain, and joint pain. Each of these items was collected on a four-point scale including, none, mild, moderate, and severe.

Time frame:
7 days post vaccination
Reported as:
Count of participants · Participants
Number of Systemic Events Within 7 Days After Vaccination
ParticipantsRSVPreFPlacebo
Number of Systemic Events Within 7 Days After Vaccination1811
SecondaryNumber of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination

Number of participants with at least one unsolicited adverse events (AEs) within 30 days after vaccination. Unsolicited AEs were all AEs for which participants were not specifically questioned in the participant diary.

Time frame:
30 days
Reported as:
Count of participants · Participants
Number of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination
ParticipantsRSVPreFPlacebo
Number of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination1210
SecondaryOccurrence of Medically Attended AEs

Number of medically attended AEs from vaccination to study end

Time frame:
Through study completion, an average of 6 months
Reported as:
Count of participants · Participants
Occurrence of Medically Attended AEs
ParticipantsRSVPreF (From Vaccination Until Viral Challenge)Placebo (From Vaccination Until Viral Challenge)RSVPreF (From Viral Challenge Until Day 28)Placebo (From Viral Challenge Until Day 28)RSVPreF (From Day 28 Until Day155)Placebo (From Day 28 Until Day155)
Occurrence of Medically Attended AEs122120
SecondaryOccurrence of SAEs

Number of SAEs from vaccination to study end

Time frame:
Through study completion, an average of 6 months
Reported as:
Count of participants · Participants
Occurrence of SAEs
ParticipantsRSVPreFPlacebo
Occurrence of SAEs11
SecondaryNumber of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge

Number of participants with at least one unsolicited AE within 30 days post-viral challenge (Day 0) up to Day +28 follow up. Unsolicited AEs were all AEs for which participants were not specifically questioned in the participant diary.

Time frame:
Day 0 to Day 28
Reported as:
Count of participants · Participants
Number of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge
ParticipantsRSVPreFPlacebo
Number of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge1417
SecondaryOccurrence of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period.

Number of hematological and biochemical laboratory assessment Abnormalities reported as AEs during the quarantine period.

Time frame:
Day -2 to Day12
Reported as:
Count of participants · Participants
Occurrence of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period.
ParticipantsRSVPreFPlacebo
Mild raised ALT85
Moderate raised ALT11
Mild raised AST25
Moderate raised AST10
Moderate raised CK01
Mild low platelets01
Mild low lymphocytes01
Moderate low neutrophils01
SecondaryUse of Concomitant Medication

Concomitant medications (prescription and over the counter drugs and supplements that a study participant had taken alongside the study vaccination) were recorded for the period following vaccination (up to viral challenge) and from viral challenge until Day 28..

Time frame:
From Vaccination (Day -28) until Viral Challenge (Day 0), and From Viral Challenge (Day 0) until Day 28
Reported as:
Count of participants · Participants
Use of Concomitant Medication
ParticipantsRSVPreFPlacebo
Concomitant Medications from Vaccination (Day -28) until Viral Challenge (Day 0)911
Concomitant Medications from Viral Challenge (Day 0) until Day 281414

Adverse events

Collected over Adverse events (AEs) were recorded from vaccination (Day -28) up until viral challenge (Day 0 pre-challenge), following viral challenge (Day 0 post-challenge) until Day 28, and from Day 28 until Day 155. Medically attended AEs and SAEs were recorded from vaccination (Day -28) up until viral challenge (Day 0 pre-challenge), following viral challenge (Day 0 post-challenge) until Day 28, and from Day 28 until Day 155.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RSVPreF (From Vaccination Until Viral Challenge)0/35 (0%)0/35 (0%)12/35 (34.3%)
Placebo (From Vaccination Until Viral Challenge)0/35 (0%)0/35 (0%)9/35 (25.7%)
RSVPreF (From Viral Challenge Until Day 28)0/35 (0%)0/35 (0%)2/35 (5.7%)
Placebo (From Viral Challenge Until Day 28)0/35 (0%)1/35 (2.9%)1/35 (2.9%)
RSVPreF (From Day 28 Until Day155)0/35 (0%)1/35 (2.9%)2/35 (5.7%)
Placebo (From Day 28 Until Day155)0/35 (0%)0/35 (0%)0/35 (0%)
Most frequent serious events
Most frequent serious events
EventRSVPreF (From Vaccination Until Viral Challenge)Placebo (From Vaccination Until Viral Challenge)RSVPreF (From Viral Challenge Until Day 28)Placebo (From Viral Challenge Until Day 28)RSVPreF (From Day 28 Until Day155)Placebo (From Day 28 Until Day155)
MyocarditisCardiac disorders———1/350/35—
Meningitis viralInfections and infestations———0/351/35—
Most frequent other events
Showing 10 of 24
Most frequent other events
EventRSVPreF (From Vaccination Until Viral Challenge)Placebo (From Vaccination Until Viral Challenge)RSVPreF (From Viral Challenge Until Day 28)Placebo (From Viral Challenge Until Day 28)RSVPreF (From Day 28 Until Day155)Placebo (From Day 28 Until Day155)
Dry skinSkin and subcutaneous tissue disorders2/352/351/350/350/350/35
LymphadenopathyBlood and lymphatic system disorders1/350/350/350/350/350/35
PalpitationsCardiac disorders0/351/350/350/350/350/35
Abdominal painGastrointestinal disorders0/351/350/350/350/350/35
NauseaGastrointestinal disorders1/350/350/350/350/350/35
Vessel puncture site bruiseGeneral disorders0/351/350/350/350/350/35
ConjunctivitisInfections and infestations0/351/350/350/350/350/35
PharyngitisInfections and infestations1/350/350/350/350/350/35
Alanine aminotransferase increasedInvestigations0/351/351/350/350/350/35
Blood creatine phosphokinase increasedInvestigations0/351/350/350/350/350/35

Baseline characteristics

Age, Continuous
Age, Continuous(years)RSVPreFPlaceboTotal
Mean26.0 ± 6.4627.1 ± 6.7826.5 ± 6.60
Sex: Female, Male
Sex: Female, Male(Participants)RSVPreFPlaceboTotal
Female101020
Male252550
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RSVPreFPlaceboTotal
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American101
White313465
More than one race000
Unknown or Not Reported303
07

Study locations

1 site
  • Golam Kabir
    London, E1 2AX, United Kingdom
08

References and documents

Publications

  • Schmoele-Thoma B, Zareba AM, Jiang Q, Maddur MS, Danaf R, Mann A, Eze K, Fok-Seang J, Kabir G, Catchpole A, Scott DA, Gurtman AC, Jansen KU, Gruber WC, Dormitzer PR, Swanson KA. Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2022 Jun 23;386(25):2377-2386. doi: 10.1056/NEJMoa2116154. PubMed 35731653 ↗

Study documents

  • Protocol and statistical analysis plan · Jan 22, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04785612
Lead sponsor
Hvivo
Collaborators
Pfizer
Responsible party
Sponsor
First posted
Mar 8, 2021
Start date
Nov 10, 2020
Primary completion
Apr 8, 2021
Completion
Aug 16, 2021
Results posted
Aug 7, 2024
Last update
Aug 7, 2024

Study contacts

Alex Mann
study director · Hvivo
Golam Kabir, MD
principal investigator · Hvivo

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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