E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Respiratory Syncytial Virus (RSV) Infection |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory Tract Infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 collect further data on safety and effectiveness of the liquid formulation of palivizumab (Synagis® ) administered as monthly intramuscular injections among preterm infants, infants with chronic lung disease (CLD) of prematurity and infants with hemodynamically significant congenital heart disease (CHD) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Infants at high risk of severe RSV infection defined as fulfilling at least one of the following:
- Infants born ≤ 35 weeks gestational age AND are ≤ 6 months of age at enrollment;
- Infants ≤ 24 months of age at enrollment AND with a diagnosis of BPD (defined as oxygen requirement at a corrected gestational age of 36 weeks) requiring intervention/management (i.e., oxygen, diuretics, bronchodilators, corticosteroids, etc.) anytime within 6 months prior to enrollment;
- Infants ≤ 24 months of age at enrollment with hemodynamically significant CHD, either cyanotic or acyanotic, unoperated or partially
corrected. Children with acyanotic cardiac lesions must have pulmonary hypertension (≥ 40 mmHg measured pressure in the pulmonary artery
[ultrasound acceptable]) or the need for daily medication to manage CHD. Infants with following conditions are not eligible:
hemodynamically insignificant small atrial or ventricular septal defects, patent ductus arteriosus, children with aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone.
2. Informed Consent Form signed by parent(s)/legal guardian(s). |
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E.4 | Principal exclusion criteria |
1. Hospitalization at the time of enrollment (unless discharge is anticipated within 14 days).
2. Mechanical ventilation (including continuous positive airway pressure, CPAP) at the time of enrollment.
3. Life expectancy < 6 months.
4. Unstable cardiac or respiratory status, including cardiac defects so severe that survival is not expected or for which cardiac transplantation is planned or anticipated.
5. Active respiratory illness, or other acute infection.
6. Known renal impairment (e.g., ≥ 25% decrease in age appropriate creatinine clearance), as determined by the Investigator.
7. Known hepatic impairment (e.g., albumin < 2.0 g/dL), as determined by the Investigator.
8. Unstable neurological disorder (includes, but is not restricted to epilepsy and, decompensated hydrocephaly).
9. Known immunodeficiency, including Human Immunodeficiency Virus (HIV) infection as determined by the Investigator
10. Mother with known HIV infection unless the child has been proven to be not infected with HIV
11. Allergy to immunoglobulin products
12. Prior receipt of RSV vaccine or prophylaxis (e.g., palivizumab); or administration of a product possibly containing RSV-neutralizing antibody or any other polyclonal antibody within 100 days prior to enrollment (includes, but is not restricted to, the following: RSV hyperimmunoglobulin, polyclonal intravenous immunoglobulin, cytomegalovirus hyperimmunoglobulin, varicella zoster hyperimmunoglobulin).
13. Previous enrollment in this trial.
14. Subject is currently participating in another investigational study (drug or device) or has participated in an investigational drug study (i.e., receiving or has received investigational product) within 1 month or 5 times the investigational drug half-life, whichever is longer, prior to enrolment.
15. For any reason, subject is considered by the investigator to be an unsuitable candidate for this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number and proportion of subjects with RSV-hospitalization along with the 95% exact confidence interval for the proportion. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 30 days of the last study drug dose. |
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E.5.2 | Secondary end point(s) |
Length of hospital stay, use and duration of oxygen supplementation, use and duration of mechanical ventilation, and admission to and duration of ICU will be summarized descriptively for all subjects with RSV hospitalization (including new onset of nosocomial respiratory/cardiac symptoms). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Within 30 days of the last study drug dose. |
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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 | 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) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Belarus |
Russian Federation |
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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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The date of the last subject's follow-up contact, which is defined as 100 days following the final injection of palivizumab. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 8 |