Palivizumab for Prevention of Severe Respiratory Syncytial Virus Infection in Russian Children

A prospective, multicenter, open-label, non-comparative study of safety and efficacy of palivizumab (Synagis) 15 mg/kg intramuscularly as prophylaxis to severe lower respiratory tract respiratory syncytial virus infection in 100 Russian children of 2 years of age and less in high-risk populations (preterm infants \[less than or equal to 35 weeks gestational age\], infants with bronchopulmonary dysplasia \[BPD\], and infants with hemodynamically significant congenital heart disease \[HSCHD\]).

• palivizumab (Biological), also known as ABT-315 (MEDI-493), Synagis 15 mg/kg intramuscularly: palivizumab 15 mg/kg intramuscularly

Primary outcomes

• Frequency of Adverse Events [Through 30 days following the last injection of palivizumab]: Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 and 100 days after the last dose of study drug. The number of subjects experiencing a serious or nonserious treatment-emergent adverse event within 30 days after the last dose of study drug is summarized. See the Reported Adverse Events section for details.
• Number of Hospitalizations Due to Respiratory Syncytial Virus (RSV) [Through 30 days following the last injection of palivizumab]: Number of subjects experiencing an RSV hospitalization

Secondary outcomes

• Total Number of RSV Hospitalization Days [Through 30 days following the last injection of palivizumab]: All secondary outcome measures were related to hospitalization due to RSV infection. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.
• Total RSV Hospitalization Days With Increased Supplemental Oxygen Requirement [Through 30 days following the last injection of palivizumab]: All secondary outcome measures were related to hospitalization due to RSV infection. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.
• Number of Intensive Care Unit (ICU) Admissions During RSV Hospitalization [Through 30 days following the last injection of palivizumab]: Outcome measure refers to the number of subjects admitted to the ICU during RSV hospitalization. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.
• Total Days of RSV ICU Stay [Through 30 days following the last injection of palivizumab]: All secondary outcome measures were related to hospitalization due to RSV infection. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.
• Number of Subjects Who Received Mechanical Ventilation During RSV Hospitalization [Through 30 days following the last injection of palivizumab]: All secondary outcome measures were related to hospitalization due to RSV infection. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.
• Total Days of Mechanical Ventilation During RSV Hospitalization [Through 30 days following the last injection of palivizumab]: All secondary outcome measures were related to hospitalization due to RSV infection. No RSV hospitalizations occurred during the study; therefore, evaluation of the secondary outcome measures was not possible.

Sex: All, ages: any to 2 Years

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled into the study:

1. Infants at high risk of severe RSV infection defined as fulfilling at least one of the following:

   * Infants born at less than or equal to 35 weeks gestational age AND are less than or equal to 6 months of age at enrollment
   * Infants less than or equal to 24 months of age at enrollment AND with a diagnosis of bronchopulmonary dysplasia (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 less than or equal to 24 months of age at enrollment with hemodynamically significant congenital heart disease, either cyanotic or acyanotic, unoperated or partially corrected. Children with acyanotic cardiac lesions must have pulmonary hypertension (greater than or equal to 40 mmHg measured pressure in the pulmonary artery \[ultrasound acceptable\]) or the need for daily medication to manage congenital heart disease. Children with the following conditions are not eligible: hemodynamically insignificant small atrial or ventricular septal defects, patent ductus arteriosis, children with aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone.
2. Informed Consent Form signed by parent(s).

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for the study:

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 less than 6 months.
4. Active respiratory illness, or other acute infection.
5. Known renal impairment, as determined by the investigator.
6. Known hepatic impairment, as determined by the investigator.
7. History of seizures (except neonatal seizures).
8. Unstable neurological disorder (includes, but is not restricted to, epilepsy and decompensated hydrocephaly).
9. Known immunodeficiency, as determined by the investigator.
10. Allergy to immunoglobulin products.
11. Prior receipt of RSV vaccine or prophylaxis (e.g., palivizumab or motavizumab), or administration of a product possibly containing RSV-neutralizing 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).
12. Participation in another clinical trial within 30 days prior to enrollment.
13. Previous enrollment in this trial.
14. For any reason, subject is considered by the investigator to be an unsuitable candidate for this study.

Participant flow

Outcome results

• Frequency of Adverse Events (Primary), Number, participants: Palivizumab 41
• Number of Hospitalizations Due to Respiratory Syncytial Virus (RSV) (Primary), Number, participants: Palivizumab 0 (0.0 to 3.6)
• Total Number of RSV Hospitalization Days (Secondary), Mean, days
• Total RSV Hospitalization Days With Increased Supplemental Oxygen Requirement (Secondary), Mean, days
• Number of Intensive Care Unit (ICU) Admissions During RSV Hospitalization (Secondary), Number, participants
• Total Days of RSV ICU Stay (Secondary), Mean, days
• Number of Subjects Who Received Mechanical Ventilation During RSV Hospitalization (Secondary), Number, participants
• Total Days of Mechanical Ventilation During RSV Hospitalization (Secondary), Mean, days

Adverse events

Time frame: From date of first dose of study drug through 100 days after the last dose of study drug

Serious adverse events by term

Other adverse events by term

Limitations and caveats: This study had no control group; relative comparisons are only possible with current product information for palivizumab. No RSV hospitalizations occurred during the study; therefore, secondary outcome measures could not be evaluated.

• Results publication: Turti TV, Baibarina EN, Degtiareva EA, Keshishyan ES, Lobzin YV, Namazova-capital VE, Cyrillicaranova LS, Prodeus AP, Gudkov KM, Kruglova AI, Schulz GA, Notario GF. A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation. BMC Res Notes. 2012 Sep 4;5:484. doi: 10.1186/1756-0500-5-484. PMID 22943074

• Konstantin M Gudkov, MD, Study director, Abbott