Clinical trial NCT04785612: Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: Hvivo
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2021-03-08
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

  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:

* 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.

Primary outcomes:
measure: Area Under the Viral Load-time Curve (VL-AUC) of RSV
timeFrame: Day 2 to Day 12
measure: Number of Participants With RT-PCR Confirmed (Detected) Incidence of Symptomatic Infection
timeFrame: Day 2 to Day 12
measure: Sum Total Symptoms Diary Card Score (TSS)
timeFrame: Day 1 to Day 12
Secondary outcomes:
measure: Number of Participants With RT-PCR Confirmed (Quantifiable) Incidence of Symptomatic Infection
timeFrame: Day 2 to Day 12
measure: Number of Participants With Culture Lab-confirmed Reduction of Symptomatic RSV Infection
timeFrame: Day 2 to Day 12
measure: Peak Viral Load of RSV by qRT-PCR
timeFrame: Day 2 to Day 12
measure: Peak Viral Load of RSV by Viral Culture
timeFrame: Day 2 to Day 12
measure: Duration of Quantifiable qRT-PCR Measurements
timeFrame: Day 2 to Day 12
measure: Duration of Quantitative Viral Culture Measurements
timeFrame: Day 2 to Day 12
measure: VL-AUC Determined by Quantitative Viral Culture
timeFrame: Day 2 to Day 12
measure: Area Under the Curve Over Time of Total Clinical Symptoms (TSS-AUC)
timeFrame: Day 1 to Day 12
measure: Peak Symptoms Diary Card Score
timeFrame: Day 1 to Day 12
measure: Peak Daily Symptom Score
timeFrame: Day 1 to Day 12
measure: Percentage Number of Participants With Grade 2 or Higher Symptoms
timeFrame: Day 1 to Day 12
measure: Number of Participants With an Occurrence of at Least Two Positive Quantifiable qRT-PCR Measurements on 2 or More Consecutive Days
timeFrame: Day 2 to Day 12
measure: Number of Participants With an Occurrence of at Least Two Positive Detectable qRT-PCR Measurements on 2 or More Consecutive Days
timeFrame: Day 2 to Day 12
measure: Number of Participants With an Occurrence of at Least One Positive Quantitative Cell Culture Measurements
timeFrame: Day 2 to Day 12
measure: Total Mucus Weight
timeFrame: Day 1 to Day 12
measure: Total Tissue Number
timeFrame: Day 1 to Day 12
measure: Number of Solicited Local Reactions Within 7 Days After Vaccination
timeFrame: 7 days post vaccination
measure: Number of Systemic Events Within 7 Days After Vaccination
timeFrame: 7 days post vaccination
measure: Number of Participants With an Occurrence of Unsolicited Adverse Events (AEs) Post Vaccination
timeFrame: 30 days
measure: Occurrence of Medically Attended AEs
timeFrame: Through study completion, an average of 6 months
measure: Occurrence of SAEs
timeFrame: Through study completion, an average of 6 months
measure: Number of Participants With an Occurrence of Unsolicited AEs Related to Viral Challenge
timeFrame: Day 0 to Day 28
measure: Occurrence of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period.
timeFrame: Day -2 to Day12
measure: Use of Concomitant Medication
timeFrame: From Vaccination (Day -28) until Viral Challenge (Day 0), and From Viral Challenge (Day 0) until Day 28
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Golam Kabir
Study officials:
affiliation: Hvivo
name: Alex Mann
role: STUDY_DIRECTOR
affiliation: Hvivo
name: Golam Kabir, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.