Synagis® Liquid 50mg, 100mg for Intramuscular Injection Special Investigation in Immunocompromised Children With Synagis®

This post marketing observational study (PMOS) was conducted in Japan during the 2013-2014 and 2014-2015 Respiratory Syncytial Virus (RSV) seasons to assess the safety and effectiveness of palivizumab for the prevention of serious lower respiratory tract infection caused by RSV in participants 24 months of age and under, who have an immunocompromised medical condition (e.g., combined immunodeficiency disease, antibody deficiency, or other types of immunodeficiency; HIV infection; recovering from organ or bone marrow transplantation; on chemotherapy; on high-dose corticosteroid therapy; on immunosuppressants) or who have Down syndrome.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infection

Detailed Description

Palivizumab was prescribed according to the local label and independently of the decision to enroll participants in the study. Palivizumab was administered monthly throughout the Respiratory Syncytial Virus (RSV) infection seasons via intramuscular injection at a dose of 15 mg/kg of body weight. Survey forms were collected after the observation period. The number of adverse events and the frequency of hospitalizations due to RSV infections in surveyed participants were assessed to evaluate the safety and effectiveness of palivizumab.

• Study Type: Observational
• Enrollment (Actual): 312

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Single-arm, Multi-center, Prospective Cohort

Description

Inclusion Criteria:

1. Availability of a parent or legal guardian who was capable and willing to give written informed consent for his/her newborn, infant or young child to participate in the study
2. Participants receiving palivizumab for prevention of serious lower respiratory tract disease caused by RSV infection

3. Newborns, infants, or young children 24 months of age and under who have an immunocompromised medical condition:

   • combined immunodeficiency, (severe combined immunodeficiency, X-linked hyper-immunoglobulin M (IgM) syndrome, etc.), antibody deficiency (X-linked agammaglobulinemia,common variable immunodeficiency, non-X-linked hyper-IgM syndrome,etc.) or other immunodeficiency (Wiskott-Aldrich syndrome, etc.)
   • acquired T cell dysfunction ( such as human immunodeficiency virus (HIV) infection etc.)
   • history of past organ transplantation
   • history of past bone marrow transplantation
   • receiving immunosuppressive chemotherapy
   • receiving systemic high-dose corticosteroid therapy (prednisone equivalents ≥ 0.5 mg/kg/every other day, other than inhaler or topical use), or
   • receiving other immunosuppressive therapy (azathioprine, methotrexate, mizoribine, mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus, cytokine inhibitors, etc.)
   • receiving biologics (including cytokine inhibitors)
   • Others (nephrotic syndrome, chronic peritoneal dialysis, hemodialysis)
4. Newborns, infants, or young children age of 24 months and under who have Down syndrome without a current hemodynamically significant Congenital Heart Disease. The participant must have had an experience with persistent respiratory symptoms or regular outpatient treatment due to respiratory tract infection prior to current RSV season.

Exclusion criteria:

1. Participants included in the Contraindications section of the package insert
2. Participants with known hypersensitivity to the ingredients of palivizumab
3. Participants with a known positive RSV infection before hospitalization

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Immunocompromised children; Children with immunocompromised conditions or Down syndrome at high-risk of serious RSV disease who received palivizumab during the RSV season

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. Adverse events were documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Number of Participants With Serious Adverse Events	A serious adverse event was defined as any untoward medical occurrence in a participant that the investigator believed to be causally related to the study treatment and met at least one of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or important medical event requiring medical or surgical intervention to prevent serious outcome. Serious adverse events were documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Number of Participants With Adverse Drug Reactions	An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with their treatment. If a causal relationship with palivizumab was: "Related", "Causality cannot be ruled out", or "Not assessable" as determined by the investigator, it was classified as an adverse drug reaction (ADR). An AE was considered a serious adverse event (SAE) and a serious adverse drug reaction (SADR) if the severity of the AE or ADR was any one of the following, as determined by the investigator: "Death", "Life-threatening condition", "Hospitalization or prolonged hospitalization", "Persistent or significant disability", or "Other medically important condition". Information about AEs and ADRs was documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lower Respiratory Tract Infection (LRI) Score During the Study	The Lower Respiratory Tract Infection (LRI) Score ranged from 0 (well or baseline); 1 (Upper Respiratory tract Infection [URI]), mild); 2 (LRI); 3 (LRI, moderate); 4 (LRI, severe) to 5 (Respiratory Failure). Components of the score included respiratory rate per minute, oxygen saturation, and physical findings of LRI. LRI scores were documented on the case report form (CRF).	From the first administration of palivizumab up to the last administration of palivizumab, up to 36 weeks
Number of Participants Hospitalized Due to Respiratory Syncytial Virus (RSV) Infection	Hospitalization due to RSV infection or the presence/absence of positive RSV antigen test results during hospitalization was documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Mean Hospitalization Length Due to Respiratory Syncytial Virus (RSV) Infection	The date of hospitalization due to RSV infection and the date of hospital discharge were documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Number of Hospitalized Participants Requiring Respiratory Support	The presence/absence of respiratory support, (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) the start and end dates of respiratory support, and the dates of hospitalization and discharge were documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks
Mean Duration of Respiratory Support	The presence/absence of respiratory support (oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, and other mechanical respiratory support or Intensive Care Unit admission) and the start and end dates of respiratory support were documented on the case report form (CRF).	From the first administration of palivizumab to 30 days after the last administration of palivizumab, up to 44 weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Osamu Mikami, MD, PhD, AbbVie GK.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 20, 2013

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Down Syndrome; Immunocompromised; Respiratory syncytial virus (RSV) infection; Prevention of severe RSV infection; Effectiveness of palivizumab
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: P14-296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO