| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Respiratory Syncytial Virus Infection |
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| E.1.1.1 | Medical condition in easily understood language |
| RSV is a common virus that can cause severe chest infections in small children, adults with heart, lung and immune system conditions and elderly people |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the effect of the RSVpreF vaccine, in reducing the incidence and severity of infection or disease due to RSV-A Memphis 37b when compared to placebo. |
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| E.2.2 | Secondary objectives of the trial |
•To further evaluate the effect of RSVpreF, in reducing the incidence of infection or disease due to RSV compared to placebo.
•To further evaluate the effect of RSVpreF, in reducing infection due to RSV compared to placebo.
•To further evaluate the effect of RSVpreF, in reducing the incidence of RSV infection compared to placebo.
•To further evaluate the effect of RSVpreF, in reducing symptoms due to RSV compared to placebo.
•To evaluate the effect of RSVpreF, in reducing nasal discharge when compared to placebo.
•To evaluate the safety of RSFpreF when compared to placebo.
•To evaluate the safety of the RSV challenge model. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. An informed consent document signed and dated by the participant and the Investigator.
2. Aged between 18 and 50 years old on the day of signing the consent form.
3. 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, as defined by medical history, physical examination, (including vital signs), ECG, and routine laboratory tests as determined by the Investigator.
4. A documented medical history prior to enrolment.
5. The following criteria are applicable to female participants participating in the study.
a) Females of childbearing potential must have a negative pregnancy test prior to enrolment.
b) Females of non-childbearing potential:
a. 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).
6. The following criteria apply to female and male participants:
a) 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). Highly effective contraception is as described below:
a. Established use of hormonal methods of contraception described below (for a minimum of 2 weeks prior to the first study visit). When hormonal methods of contraception are used, male partners are required to use a condom with a spermicide:
i. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
1. oral
2. intravaginal
3. transdermal
ii. progestogen-only hormonal contraception associated with inhibition of ovulation:
1. oral
2. injectable
3. implantable
b. Intrauterine device (IUD)
c. Intrauterine hormone-releasing system (IUS)
d. Bilateral tubal ligation
e. Male sterilisation (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate) where the vasectomised male is the sole partner for that woman.
f. 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.
b) 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.
d. 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.
c) 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).
7. Sero-suitable to the challenge virus, as defined in the study Analytical Plan.
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| E.4 | Principal exclusion criteria |
1. 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.
2.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).
3. 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]).
4. A total body weight ≤ 50 kg and Body Mass Index (BMI) ≤18 kg/m2 and ≥35kg/m2.
5. Females who:
a. Are breastfeeding, or
b. Have been pregnant within 6 months prior to the study.
6. History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
7. Venous access deemed inadequate for the phlebotomy and cannulation demands of the
study.
8. a. Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge, (historical nasal polyps can be included, but large nasal polyps causing current and significant symptoms and/or requiring regular treatments in the last month will be excluded).
b. Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first study visit and/or history of being hospitalized due to epistaxis on any previous occasion.
c. Any nasal or sinus surgery within 3 months of the first study visit.
9.Unless medically necessary (e.g. during an outbreak or pandemic situation) and at the PI’s discretion
a) Evidence of vaccinations within the 4 weeks prior to the planned date of viral
challenge/first dosing with IMP (whichever occurs first).
b) Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No
travel restrictions will apply after the Day 28 Follow-up visit).
10. 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.
11.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.
12. 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 (weekly intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small glass of wine or a measure of spirits), or excessive consumption of xanthine containing substances (e.g. daily intake in excess of 5 cups of caffeinated drinks e.g. coffee, tea, cola).
13. A forced expiratory volume in 1 second (FEV1) < 80%.
14. Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test.
15. Those employed or immediate relatives of those employed at hVIVO or Pfizer or vendors.
16. Any other finding that, in the opinion of the Investigator, deems the Participant unsuitable for the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
To evaluate the reduction in one or more of the following endpoints within the primary endpoint family:
• Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by qRT-PCR on nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine.
• RT-PCR-confirmed symptomatic RSV infection (Variant 1), defined as:
o RT-PCR-confirmed RSV infection [(two detectable (≥LLOD) qRT-PCR measurements (reported on 2 or more consecutive days), starting two days post-viral challenge (Day +2) up to discharge from quarantine].), AND
o Either one or more positive clinical symptoms of any grade from two different categories in the symptom scoring system (Upper Respiratory, Lower Respiratory, Systemic), or one Grade 2 symptom from any category.
• Sum total symptoms diary card score: sum total clinical symptoms (TSS) as measured by graded symptom scoring system collected three times daily starting one days post-viral challenge (Day +1) up to discharge from quarantine
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Nasal samples for the measure of viral load will be collected twice daily during the quarantine phase of the study starting from study Day 2 up to discharge.
Symptoms will be recorded daily by participants during the quarantine phase from admission to discharge. |
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| E.5.2 | Secondary end point(s) |
• RT-PCR-confirmed symptomatic RSV infection and culture lab-confirmed reduction of symptomatic RSV infection in nasal samples.
• To evaluate the reduction in Peak viral load determined by qRT-PCR and by quantitative viral culture measurements in nasal samples.
• Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by quantitative viral culture on nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to discharge from quarantine.
• Duration of RSV-A Memphis 37b quantifiable qRT-PCR measurements and viral culture measurements in nasal samples.
To evaluate the reduction in the following endpoints:
• Area under the curve over time (TSS-AUC) of total clinical symptoms (TSS) as measured by graded symptom scoring system (categorical and visual analogue scales) collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine.
• Peak symptoms diary card score: peak total clinical symptoms (TSS) as measured by graded symptom scoring system (categorical and visual analogue scales) collected three times daily starting one day post-viral challenge (Day +1) up to discharge from quarantine
• 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.
• Number (%) of participants with Grade 2 or higher symptoms
To evaluate the reduction in the following endpoints:
• Occurrence of at least two positive quantifiable (≥LLOQ) qRT-PCR
measurements in nasal samples at different timepoints reported on 2 or more
consecutive days starting two days post-viral challenge (Day +2) up to discharge from quarantine.
• Occurrence of at least two positive detectable (≥LLOD) qRT-PCR measurements in nasal samples at different timepoints reported on 2 or more consecutive days starting two days post-viral challenge (Day +2) up to discharge from quarantine.
• Occurrence of at least one positive quantitative (≥LLOQ) cell culture measurement in nasal samples starting two days post-viral challenge (Day +2) up to discharge from quarantine.
To evaluate the reduction in the following endpoints:
• Total weight of mucus produced starting one day post-viral challenge (Day +1) up to discharge from quarantine.
• Total number of tissues used by participants starting one day post-viral challenge (Day +1) up to discharge from quarantine.
To evaluate the incidence of the following endpoints:
• Occurrence of solicited local reactions and systemic events within 7 days (i.e., on the day of vaccination and 6 subsequent days) after vaccination.
• Occurrence of unsolicited adverse events (AEs) within 30 days (i.e., on the day of vaccination and 29 subsequent days) after vaccination
• Occurrence of medically attended AEs (MAEs) and serious adverse events (SAEs) from vaccination (Day -28) up to study end (Day +155).
To list the incidence of the following endpoints:
o Occurrence of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day +28 follow up.
o Occurrence of SAEs related to the viral challenge from the viral challenge (Day 0) up to Day +28 follow up.
o Occurrence of haematological and biochemical laboratory abnormalities during the quarantine period.
• Use of concomitant medications within 30 days post-viral challenge (Day 0 up to Day +28 follow up).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Nasal samples for the measure of viral load will be collected twice daily during the quarantine phase of the study starting from study Day 2 up to discharge.
2- Symptoms will be recorded daily by participants during the quarantine phase from admission to discharge.
3- Paper tissues are collected daily during the quarantine phase.
4- Solicited AEs are recorded for a total of 7 days post vaccination
5- Unsolicited AEs are recorded for 30 days post vaccination
6- AEs are recorded throughput the study.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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