E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The prevention of medically attended RSV LRTI. |
|
E.1.1.1 | Medical condition in easily understood language |
To prevent serious lower respiratory tract infection caused by RSV. |
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066742 |
E.1.2 | Term | Respiratory syncytial virus infection prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
|
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 safety and tolerability of MEDI8897 compared to palivizumab when administered to high-risk infants eligible to receive palivizumab entering their first RSV season and children with chronic lung disease (CLD) or congenital heart disease (CHD) entering their first and second RSV season. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate serum concentrations of MEDI8897 and palivizumab 2. To evaluate ADA responses to MEDI8897 and to palivizumab in serum 3. To assess the descriptive efficacy of MEDI8897 when administered as a single IM dose in the first RSV season or a single IM dose administered in the second RSV season, in reducing medically attended LRTI (inpatient and outpatient) and hospitalization due to RT-PCR-confirmed RSV, compared to palivizumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria: 1. For the preterm cohort (excluding subjects with CLD or hemodynamically significant CHD): preterm infants in their first year of life and born ≤ 35 weeks 0 days GA eligible to receive palivizumab in accordance with national or local guidelines, including those with: (a) Uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, or (b) Aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone 2. For the CLD/CHD cohort: (a) Subjects with CLD - infants in their first year of life and a diagnosis of CLD of prematurity requiring medical intervention/management (ie, supplemental oxygen, bronchodilators, or diuretics) within the 6 months prior to randomization (b) Subjects with CHD - infants in their first year of life and documented, hemodynamically significant CHD (must be unoperated or partially corrected CHD) Note: Infants with hemodynamically significant acyanotic cardiac lesions must have pulmonary hypertension (≥ 40 mmHg measured pressure in the pulmonary artery) or the need for daily medication to manage CHD 3. Infants who are entering their first RSV season at the time of screening 4. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the USA, EU Data Privacy Directive in the EU) obtained from the subject's parent(s)/legal representative(s) prior to performing any protocol-related procedures, including screening evaluations 5. Subject's parent(s)/legal representative(s) able to understand and comply with the requirements of the protocol including follow-up and illness visits as judged by the investigator 6. Subject is available to complete the follow-up period, which will be 1 year after Season 1/ Dose 1 for subjects without CLD/CHD, or 1 year after Season 2/Dose 1 (or last replacement dose as applicable for CHD) for subjects with CLD/CHD |
|
E.4 | Principal exclusion criteria |
Any of the following would exclude the subject from participation in the study: 1. Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to randomization 2. Any history of LRTI or active LRTI prior to, or at the time of, randomization 3. Known history of RSV infection or active RSV infection prior to, or at the time of, randomization 4. Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization 5. Requirement for mechanical ventilation, extracorporeal membrane oxygenation, CPAP, or other mechanical respiratory or cardiac support at the time of randomization 6. Anticipated cardiac surgery within 2 weeks after randomization 7. Anticipated survival of < 6 months after randomization 8. Receipt of any investigational drug 9. Known renal impairment 10. Known hepatic dysfunction including known or suspected active or chronic hepatitis infection 11. Clinically significant congenital anomaly of the respiratory tract 12. Chronic seizure, or evolving or unstable neurologic disorder 13. Prior history of a suspected or actual acute life-threatening event 14. Known immunodeficiency, including human immunodeficiency virus (HIV) 15. Mother with HIV infection (unless the child has been proven to be not infected) 16. Any known allergy, including to immunoglobulin products, or history of allergic reaction 17. Receipt of palivizumab or other RSV mAb or any RSV vaccine, including maternal RSV vaccination 18. Receipt of any monoclonal or polyclonal antibody (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study 19. Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results 20. Concurrent enrollment in another interventional study 21. Children of employees of the sponsor, clinical study site, or any other individuals involved with the conduct of the study, or immediate family members of such individuals |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of MEDI8897 as assessed by the occurrence of all treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and new onset chronic diseases (NOCDs). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Occurrence of all TEAEs, TESAEs, AESIs, and NOCDs, will be assessed through the follow-up period (Day 361). |
|
E.5.2 | Secondary end point(s) |
1. a. MEDI8897 and palivizumab serum concentrations b. MEDI8897 and palivizumab PK parameters: Summary of serum concentrations and estimated PK parameters (Cmax, AUC, apparent clearance, and t1/2, if data permit) 2. Incidence of ADA to MEDI8897 and palivizumab in serum 3. a. Incidence of medically attended LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV through 150 days after Dose 1 for Season 1 and Season 2 b. Incidence of hospitalizations due to RT-PCR-confirmed RSV through 150 days after Dose 1 for Season 1 and Season 2 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Blood will be collected to evaluate the PK of MEDI8897 and palivizumab in serum at screening and on Day 15, Day 151, Day 361 and as needed (PK samples will be collected for subjects hospitalised with LRTI) for season 1 and season 2 (CLD/CHD Cohort Only). Subjects requiring a replacement dose of study drug due to cardiac surgery with cardiopulmonary bypass will have a blood sample collected before and after surgery (prior to administering replacement dose) for PK evaluation. 2. ADA will be measured at screening and on Day 151 and Day 361 and as needed (ADA samples will be collected for subjects hospitalised with LRTI). 3. Incidence of LRTI and hospitalizations due to RSV will be monitored through Day 151 post dose in Season 1 and Season 2. |
|
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 | Yes |
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 | No |
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) | Yes |
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 | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 117 |
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 |
Chile |
Colombia |
Mexico |
Panama |
South Africa |
Turkey |
Estonia |
Argentina |
Austria |
Belgium |
Bulgaria |
Canada |
Czechia |
Finland |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
New Zealand |
Poland |
Russian Federation |
Spain |
Sweden |
Ukraine |
United Kingdom |
United States |
France |
|
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
|
The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |