| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| MEDI-534 is being investigated for the prevention of respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (hPIV3) infections and disease in young children and infants. |
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| E.1.1.1 | Medical condition in easily understood language |
| The respiratory syncytial virus and parainfluenza virus type 3 are important causes of bronchiolitis (inflammation of the small airways in the lungs) and pneumonia in infants and young children. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061603 |
| E.1.2 | Term | Respiratory syncytial virus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061907 |
| E.1.2 | Term | Parainfluenzae virus infection |
| 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 |
| The primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 at 5.0 log10 or 6.0 log10 TCID50 in RSV and hPIV3 seronegative children 6 to < 24 months of age and at dosages of 4.0 log10, 5.0 log10 or 6.0 log10 TCID50 in unscreened infants 2 months of age. |
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: (i) to describe the incidence and magnitude of MEDI-534 vaccine-like virus shedding after each dose; (ii) to evaluate the immune response generated by multiple doses of MEDI-534; (iii) to evaluate the genotypic stability of recovered vaccine virus; and (iv) to describe the incidence of serious RSV disease in vaccinated subjects over a 1 year follow-up after receipt of first dose of study vaccine
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria:
1. Male or female whose age on the day of randomization falls within one of the two age groups: Cohorts 1 and 2: 6 to < 24 months (≥6 months of age and not yet reached their 2nd year birthday);
Cohorts 3, 4, and 5: 2 months +/- 4 weeks
2. Cohorts 1 and 2 only: Subject is seronegative to both RSV and hPIV3 at screening
3. Subject whose gestational age was ≥ 36 weeks
4. Subject is in general good health with normal growth (ie, body weight > 3rd percentile per WHO simplified weight-per-age field tables)
5. Subject’s legal representative is available by telephone
6. Written informed consent obtained from the subject’s legal representative
7. Subject’s legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator
8. Subject is available to complete the follow-up period, which will be 1 year after receipt of the first dose of study vaccine
9. Subject’s legal representative must be willing and able to bring the subject to the study site for evaluation of respiratory illness in accordance with the protocol |
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| E.4 | Principal exclusion criteria |
Subjects must have none of the following:
1. Any fever (greater than or equal to 100.4°F [greater than or equal to 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization
2. Moderate or severe nasal congestion that, in the investigator’s opinion, could interfere with intranasal delivery of study vaccine
3. Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
4. Any drug therapy (chronic or other) within 7 days prior to randomization or expected receipt through 28 days after each study vaccine dosing, except that infrequent use of over-the-counter medications for the systemic treatment of common childhood symptoms (eg, pain relievers, decongestants or cough suppressants) are permitted according to the judgment of the investigator
5. Any current or expected receipt of immunosuppressive agents including steroids (greater than or equal to 2 mg/kg per day of prednisone or its equivalent, or greater than or equal to 20 mg/day if the subject weighs > 10 kg, given daily or on alternate days for greater than or equal to 14 days); children in this category should not receive study vaccine until immunosuppressive agents including corticosteroid therapy have been discontinued for greater than or equal to 30 days; the use of topical steroids is permitted according to the judgment of the investigator
6. History of receipt of blood transfusion or expected receipt through the protocol-specified blood collection at 28 days after final study dosing
7. History of receipt of immunoglobulin products or expected receipt through the protocol-specified blood collection at 28 days after final study dosing
8. Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 180 days after final study dosing
9. Receipt of any live virus vaccine (excluding oral polio vaccine and rotavirus vaccine) within 28 days prior to randomization or expected receipt within a 28-day window around any study vaccine dose
10. Receipt of any inactivated (ie, non-live) vaccine or oral polio vaccine or rotavirus vaccine within 14 days prior to randomization or expected receipt within a 14-day window around any study vaccine dose
11. Known or suspected immunodeficiency, including HIV infection
12. Expected to be living in the same home or enrolled in the same classroom at day care with infants < 6 months within 28 days after each dose
13. Living in a household with another child who is concurrently enrolled in a study of a live viral vaccine (including this study)
14. Expected contact with a pregnant caregiver within 28 days after each dose
15. A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after any study vaccine dose
16. Expected household contact within 28 days after each dose with a health care provider for immunocompromised patients or who is a day care provider for infants under the age of 6 months
17. History of allergic reaction to any component of the study vaccine
18. Previous medical history, or evidence, of an intercurrent or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject
19. Known or suspected active or chronic hepatitis infection
20. History of medical diagnosis of asthma, reactive airway disease, wheezing requiring medication, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation for respiratory illness (excludes elective mechanical ventilation during surgery for subjects in Cohorts 1 and 2)
21. Family member or household contact who is an employee of the research center or otherwise involved with the conduct of the study
22. Any condition that, in the opinion of the investigator, might interfere with study vaccine evaluation |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints of safety and tolerability of MEDI-534 will be measured by:
• Incidence of solicited symptoms from administration of study vaccine through 28 days following each dose
• Incidence of adverse events (AEs) from administration of study vaccine through 28 days following each dose
• Incidence of MA-LRIs from administration of study vaccine through 28 days following each dose
• Incidence of SAEs from administration of study vaccine through 28 days following each dose |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Through study day 28 post each dose |
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| E.5.2 | Secondary end point(s) |
The secondary endpoints include the following:
• Incidence and magnitude of vaccine-like viral shedding of MEDI-534 at Days 7, 12, and 28 after each dose for each treatment group.
• Percentage of subjects with a seroconversion to RSV and hPIV3 after the final dose (defined as a ≥ 4-fold rise from baseline in neutralizing antibody titer, regardless of baseline serostatus)
• Description of the genotypic stability of recovered vaccine virus
• Description of the potential for immunologic enhancement of RSV disease by evaluation of MA-LRIs associated with RSV infection from first administration of study vaccine through the entire study follow-up period
• Description of SNMCs from first administration of study vaccine through the end of the study follow-up period
• Description of SAEs from first administration of study vaccine through the end of the study follow-up period
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Varies, but includes through study follow-up |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| 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 | Yes |
| 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 |
| Evaluation of vaccine-like viral shedding and genotypic stability of recovered vaccine virus. |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| 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 | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Belgium |
| Brazil |
| Canada |
| Finland |
| Germany |
| Israel |
| South Africa |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| Subjects will be considered to have completed the study if they were followed up through the entire 1 year study follow-up period. The end of trial is defined as the date when the last subject has completed the study. |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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