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Trial record 1 of 6 for:    pfizer | RSV Infection
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Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04785612
Recruitment Status : Completed
First Posted : March 8, 2021
Last Update Posted : September 2, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Hvivo

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.

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Biological: RSVPreF Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double blinded, placebo-controlled study
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : November 10, 2020
Actual Primary Completion Date : April 8, 2021
Actual Study Completion Date : August 16, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
A single dose of 120 mcg RSVpreF for intramuscular injection

Placebo Comparator: Placebo
A single intramuscular injection of Placebo to match active vaccine
Other: Placebo
A single Placebo dose for intramuscular injection to match experimental vaccine




Primary Outcome Measures :
  1. 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 samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine.

  2. RT-PCR-confirmed symptomatic RSV 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 and
    • Either one or more positive clinical symptoms from different categories in the symptom scoring system or one Grade 2 symptom from any category

  3. Sum total symptoms diary card score (TSS) [ Time Frame: Day 1 to Day 12 ]
    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


Secondary Outcome Measures :
  1. RT-PCR confirmed incidence of symptomatic infection [ Time Frame: Day 2 to Day 12 ]

    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

  2. Culture lab-confirmed reduction of symptomatic RSV infection [ Time Frame: Day 2 to Day 12 ]

    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

  3. Peak viral load of RSV by qRT-PCR [ Time Frame: Day 2 to Day 12 ]
    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.

  4. Peak viral load of RSV by viral culture [ Time Frame: Day 2 to Day 12 ]
    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.

  5. Duration of quantifiable qRT-PCR measurements [ Time Frame: Day 2 to Day 12 ]
    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.

  6. Duration of quantitative viral culture measurements [ Time Frame: Day 2 to Day 12 ]
    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.

  7. VL-AUC determined by quantitative viral culture [ Time Frame: Day 2 to Day 12 ]
    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

  8. Area under the curve over time of total clinical symptoms (TSS-AUC) [ Time Frame: Day 1 to Day 12 ]
    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.

  9. Peak symptoms diary card score [ Time Frame: Day 1 to Day 12 ]
    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.

  10. Peak daily symptom score [ Time Frame: Day 1 to Day 12 ]
    Individual maximum daily sum of symptom score starting one day post-viral challenge (Day +1) up to the end of quarantine

  11. Percentage number of participants with Grade 2 or higher symptoms [ Time Frame: Day 1 to Day 12 ]
    Number (%) of participants with Grade 2 or higher symptoms

  12. Occurrence of at least two positive quantifiable qRT-PCR measurements on 2 or more consecutive days [ Time Frame: Day 2 to Day 12 ]
  13. Occurrence of at least two positive detectable qRT-PCR measurements on 2 or more consecutive days [ Time Frame: Day 2 to Day 12 ]
  14. Occurrence of at least one positive quantitative cell culture measurements on 2 or more consecutive days [ Time Frame: Day 2 to Day 12 ]
  15. Total mucus weight [ Time Frame: Day 1 to Day 12 ]
    Total weight of mucus produced starting one day post-viral challenge (Day +1) up to discharge from quarantine.

  16. Total tissue number [ Time Frame: Day 1 to Day 12 ]
    Total number of tissues used by participants starting one day post-viral challenge (Day +1) up to discharge from quarantine.

  17. Number of solicited local reactions within 7 days after vaccination [ Time Frame: 7 days ]
  18. Number of systemic events within 7 days after vaccination [ Time Frame: 7 days ]
  19. Occurrence of unsolicited adverse events (AEs) post vaccination [ Time Frame: 30 days ]
    Number of unsolicited adverse events (AEs) within 30 days after vaccination

  20. Occurrence of medically attended AEs [ Time Frame: Through study completion, an average of 6 months ]
    Number of medically attended AEs from vaccination to study end

  21. Occurrence of SAEs [ Time Frame: Through study completion, an average of 6 months ]
    Number of SAEs from vaccination to study end

  22. Occurrence of unsolicited AEs related to viral challenge [ Time Frame: Day 0 to Day 28 ]
    Number of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day +28 follow up.

  23. Occurrence of haematological and biochemical laboratory abnormalities during the quarantine period. [ Time Frame: Day -2 to Day12 ]
    Number of Safety Laboratory Assessment Abnormalities reported as AEs

  24. Use of concomitant medication [ Time Frame: within 30 days post viral challenge ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04785612


Locations
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United Kingdom
Golam Kabir
London, United Kingdom, E1 2AX
Sponsors and Collaborators
Hvivo
Pfizer
Investigators
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Study Director: Alex Mann Hvivo
Principal Investigator: Golam Kabir, MD Hvivo
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Responsible Party: Hvivo
ClinicalTrials.gov Identifier: NCT04785612    
Other Study ID Numbers: HVO-CS-005
First Posted: March 8, 2021    Key Record Dates
Last Update Posted: September 2, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Syncytial Virus Infections
Virus Diseases
Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections