| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10021881 |
| E.1.2 | Term | Infections and infestations |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| 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 determine if a single, intranasal dose of MV-012-968 is effective in reducing the frequency of symptoms and infection (with RSV) following intranasal challenge with RSV when compared to a placebo. |
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| E.2.2 | Secondary objectives of the trial |
1.To assess the effect of a single intranasal dose of MV-012-968 vaccine, in comparison with placebo [in reducing the frequency of symptomatic RSV infection, using an alternative definition for symptomatic RSV infection.]
2. To assess the effect of a single intranasal dose of MV-012-968 vaccine, in comparison with placebo [in reducing the frequency of RSV infection after intranasal challenge with RSV.]
3.To characterize the clinical profile of participants after intranasal challenge with RSV, following vaccination with a single intranasal dose of MV-012-968 compared to placebo.
4.To characterize the virologic profile of intranasally delivered RSV challenge inoculum, after vaccination with a single intranasal dose of MV-012-968 compared to placebo.
5.To assess the tolerability of a single intranasal dose of MV-012-968 vaccine during the immediate post-vaccination period.
6. To assess the safety of MV-012-968 following intranasal challenge with RSV after vaccination with a single intrana |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Informed consent
2. Aged between 18 and 45 years old on the day of signing the consent form.
3. In good general 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), Electrocardiogram (ECG), and routine laboratory tests as determined by the Investigator.
4. A documented medical history prior to enrolment.
5.Females of childbearing potential must have a negative pregnancy test prior to enrolment.
6.
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 90 days after the date of study vaccination.
b) Male participants must agree to the contraceptive requirements at study vaccination and continuing until 90 days after the date of study vaccination.
c) Male participants must agree not to donate sperm from study vaccination and until 90 days after the date of study vaccination.
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.
3.Participants who have smoked ≥ 10 pack years at any time.
4.A total body weight ≤ 50 kg, or a Body Mass Index (BMI) ≤18 kg/m2 or ≥35 kg/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.
Prior or Concomitant Medications and Assessments
9.a)Evidence of vaccinations as defined below:
o Vaccination with live attenuated vaccines within 28 days of study vaccination and viral challenge (i.e. before and after)
o Vaccination with inactivated vaccines e.g. tetanus, hepatitis A, hepatitis B, rabies) within 14 days of the study vaccination (i.e. before and after). Inactivated Influenza vaccines are allowed. If a vaccine is clinically indicated in a post-exposure setting (e.g., rabies or tetanus), it must take priority over the study vaccine.
b)Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No travel restrictions will apply after the Day 28 (±3 days) Follow-up Visit).
10. Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more of blood during the 3 months prior to the planned date of first vaccination with study vaccine or planned during the 3 months after the final visit.
11.
a) Receipt of any investigational drug within 3 months prior to the planned date of first vaccination with study vaccine.
b) Receipt of three or more investigational drugs within the previous 12 months prior to the planned date of viral challenge/first vaccination with study vaccine (whichever occurs first).
c) Prior inoculation at any time with a virus from the same virus-family as the challenge virus.
d) Inoculation within the preceding 3 months in another human viral challenge study with a respiratory virus in a different family as the current challenge virus (taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.)
e) Administration of immunoglobulins, blood products, or ribavirin in the 3 months before study vaccination
f) Use of systemic (oral, IV, IM) steroid or other systemic immunosuppressant in the 6 months before study vaccination
g) Use of corticosteroid in respiratory tract (e.g. nasal or inhaled steroid) in the 30 days before study vaccination
12.
a) Confirmed positive test for any drug of abuse 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)or excessive consumption of xanthine containing substances.
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 the Sponsor.
16. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.
17. Grade ≥ 1 laboratory abnormality on screening labs, which in the opinion of the Investigator, deems the participant unsuitable for the study. Up to two repeat assessments may be performed to confirm the abnormality prior to exclusion.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Frequency of symptomatic RSV infection (Study Days 2 through 12) as defined as the occurrence of both:
• At least 1 quantifiable plaque assay sample in nasal wash specimens
and
• Symptoms meeting either: (i) a symptom of any grade from 2 different symptom categories from the participant Symptom Diary Card [SDC] (Upper Respiratory, Lower Respiratory, Systemic) or (ii) at least 1 Grade 2 upper or lower respiratory symptom from the participant SDC. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
Efficacy
1. RSV Infection:
o Frequency of symptomatic RSV infection during post-challenge Days 2 through 12, as defined as the occurrence of both:
• 2 Quantifiable RT-qPCR samples on 2 consecutive days (i.e. at least 1 on each of 2 consecutive days) in nasal wash specimen and
• Symptoms meeting either: (i) a symptom of any grade from 2 different symptom categories from the SDC (Upper Respiratory, Lower Respiratory, Systemic) or (ii) at least 1 Grade 2 upper or lower respiratory symptom from the participant SDC.
o Frequency of RSV infection during post-challenge study Days 2 through 12 defined as the occurrence of 2 quantifiable RT-qPCR samples on 2 consecutive days (i.e. at least 1 on each of 2 consecutive days) in nasal wash specimens.
o Frequency of RSV infection defined as the occurrence of at least 1 quantifiable plaque assay sample in nasal wash specimens.
2. Clinical Symptoms
o Effect of study vaccine, MV-012-968 in the vaccine group compared to placebo on RSV symptoms (using the 11-item SDC) during post-challenge study days 2-12, with endpoints including:
• Mean daily total symptom score
• Maximal total symptom score
• Mean duration of symptoms
• Number (%) of participant with Grade 2 or higher symptoms
o Mean daily nasal discharge (mucus) weight during post-challenge study days 2-12 in vaccine group vs placebo group.
3. Viral Load:
o Additional viral load endpoints using data from RT-qPCR of nasal wash comparing vaccine vs placebo group during post-challenge study days 2 through 12:
•RSV load AREA Under the Curve (AUC)
•Peak RSV load
o Additional viral load endpoints using data from plaque assay of nasal wash comparing vaccine group vs placebo group during post-challenge study days 2 through 12:
•RSV load AUC
•Peak RSV load
o Time from RSV challenge to first of 2 consecutive (i.e. at least 1 on each of 2 consecutive days) quantifiable RT-qPCR samples in nasal wash specimens, in vaccine group vs placebo group.
o Time from RSV challenge to first quantifiable plaque assay sample in nasal wash specimens, in vaccine group vs placebo group.
4. Safety
• Number (%) of participants with solicited adverse events (AEs) as reported in the Subject Vaccination Diary Card (SVDC) during post-vaccination from study Days -28 through Day -21 in vaccine group vs placebo group, categorised by severity. Description of solicited AEs by MedDRA System Organ Class (SOC) and Preferred Term (PT).
• Number (%) of participant with unsolicited AEs during post-vaccination from study Days -28 through Day 0 in vaccine group vs placebo group, categorized by severity and by relatedness. Description of unsolicited AEs by MedDRA SOC and PT.
•Number (%) of participants with unsolicited AEs during post-challenge from study Days 1 through Day 28 in vaccine group vs placebo group, categorized by severity and by relatedness. Description of unsolicited AEs by MedDRA SOC and PT.
•Number (%) of participants with serious AEs during post-vaccination from study Days -28 through Day 152 in vaccine group vs placebo group, categorized by relatedness. Description of serious AEs by MedDRA SOC and PT.
•Number (%) of participant with medically attended AEs during post-vaccination from study Days -28 through Day 152 in vaccine group vs placebo group, categorized by relatedness. Description of AEs by MedDRA SOC and PT.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy -Study Days 2 through 12
Safety - Day -28 through Day 152 |
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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 | 7 |
| E.8.9.1 | In the Member State concerned days | 29 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 29 |
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