Clinical Study of Palivizumab in Japanese Newborns, Infants and Young Children at the Age of 24 Months or Less With Immunocompromised Medical Conditions

• Palivizumab (Drug), also known as ABT-315, Synagis

Primary outcomes

• Serum Palivizumab Trough Concentrations at Day 1, Day 31, and Day 121 [Day 1 (Screening), Day 31, Day 121]: Serum trough concentrations of palivizumab were assessed at Screening, at Day 31 (30 days after the 1st dose) and Day 121 (30 days after the 4th dose).

Secondary outcomes

• Percentage of Participants Requiring Hospitalization For Respiratory Syncytial Virus (RSV) Infection [From the first administration of palivizumab to 30 days after the last administration of palivizumab. Mean (SD) duration of treatment was 183 (37.29) days.]
• Percentage of Participants Who Required Treatment for Respiratory Syncytial Virus (RSV) Infection [From the first administration of palivizumab to 30 days after the last administration of palivizumab. Mean (SD) duration of treatment was 183 (37.29) days.]: Percentage of participants who required any of the investigated treatments (admission in the intensive care unit \[ICU\], oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure and other mechanical respiratory support) for disease caused by RSV infection after the initial dose to 30 days after the last dose of the study drug.
• Duration of Hospitalization Caused by Respiratory Syncytial Virus (RSV) Infection [From the first administration of palivizumab to 30 days after the last administration of palivizumab. Mean (SD) duration of treatment was 183 (37.29) days.]: Number of days of hospitalization caused by RSV infection.
• Duration of Required Treatment for Respiratory Syncytial Virus (RSV) Infection [From the first administration of palivizumab to 30 days after the last administration of palivizumab. Mean (SD) duration of treatment was 183 (37.29) days.]: Duration (days) of requirement for any of the investigated treatments (admission in the intensive care unit \[ICU\], oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure and other mechanical respiratory support) for disease caused by RSV infection after the initial dose to 30 days after the last dose of the study drug.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs [From the first administration of palivizumab to 100 days after the last administration of palivizumab. Mean (SD) duration of treatment was 183 (37.29) days.]: An adverse event (AE) is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): results in death or is life-threatening, results in admission or prolongation of hospitalization, results in congenital anomaly or persistent or significant disability/incapacity, or is an important medical event requiring medical or surgical intervention to prevent serious outcome. AEs were categorized by severity (mild, moderate, severe) and relationship to treatment (probably, possibly, probably not, not related). Please see Adverse Events section below for more details.
• Mean Baseline and Mean Change From Baseline in Systolic/Diastolic Blood Pressure at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]
• Mean Baseline and Mean Change From Baseline in Body Temperature at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]
• Mean Baseline and Mean Change From Baseline in Respiratory Rate at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]
• Mean Baseline and Mean Change From Baseline in Pulse Rate at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]
• Mean Baseline and Mean Change From Baseline in Body Weight at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]
• Hematology: Mean Baseline and Mean Change From Baseline in Hemoglobin at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal range for hemoglobin varied by the monthly age of the participant.
• Hematology: Mean Baseline and Mean Change From Baseline in Hematocrit at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal range for hematocrit varied by the monthly age of the participant.
• Hematology: Mean Baseline and Mean Change From Baseline in White Blood Cells (WBC), Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal ranges for WBC, neutrophils, eosinophils, basophils, lymphocytes, and monocytes varied by the monthly age of the participant.
• Hematology: Mean Baseline and Mean Change From Baseline in Red Blood Cells (RBC) and Platelet Count at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal ranges for RBC and platelet count varied by the monthly age of the participant.
• Blood Chemistry: Mean Baseline and Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal ranges for ALP, AST, and ALT varied by the monthly age of the participant.
• Blood Chemistry: Mean Baseline and Change From Baseline in Total Bilirubin, Blood Urea Nitrogen (BUN), Creatinine, and C-reactive Protein (CRP) at Day 121 [Baseline (Day 1), Day 121 (30 days after the 4th dose)]: Normal ranges for total bilirubin, BUN, creatinine, and CRP varied by the monthly age of the participant.
• Urinalysis: Presence of Urine Protein, Glucose, and Occult Blood at Screening and Day 121 [Screening, Day 121 (30 days after the 4th dose)]: The values -, -/+, 1+, 2+, 3+, and 4+ represent a range from none (-) to highest (4+) presence of protein, glucose, and occult blood in the urine. Table presents the number of participants with each value. Those categories with 0 participants to report at either time point are not included in the table below.

Sex: All, ages: any to 24 Months

Inclusion Criteria:

1. Availability of parent or legal guardian who is capable and willing to give written informed consent for his/her newborn, infant or young child to participate this study.
2. Japanese newborn, infant or young child at age of 24 months or less.
3. The subject must meet at least one of the following immunocompromised medical conditions (from \[a\] to \[h\]), and must be considered by the investigator to be a suitable candidate to receive prophylactic treatment of palivizumab:

   1. Subject has been diagnosed with 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, DiGeorge syndrome, etc.) at the time of informed consent, or
   2. Subject has been diagnosed with human immunodeficiency virus infection, or
   3. Subject has been diagnosed with Down syndrome without a current hemodynamically significant congenital heart disease at the time of informed consent (subject must have an experience with persistent respiratory symptom or regular outpatient treatment due to respiratory tract infection prior to current RSV season), or
   4. Subject has a history of post organ transplantation at the time of informed consent, or
   5. Subject has a history of post bone marrow transplantation at the time of informed consent, or
   6. Subject is receiving immunosuppressive chemotherapy at the start of study drug administration, or
   7. Subject is receiving systemic high dose corticosteroid therapy (prednisone equivalents 0.5 mg/kg or more every other day, other than inhaler or topical use) at the start of study drug administration, or
   8. Subject is receiving other immunosuppressive therapy (azathioprine, methotrexate, mizoribine, mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus, cytokine inhibitors, etc.) at the start of study drug administration.

Exclusion Criteria:

1. Subject who meets one of the palivizumab indications already approved in Japan.

   * Subject born at 28 weeks of gestation or less and who is age of 12 months or less at the start of study drug administration.
   * Subject born at 29 - 35 weeks of gestation and who is age of 6 months or less at the start of study drug administration.
   * Subject is age of 24 months or less with a history of bronchopulmonary dysplasia requiring medical management within the 6 months prior to the study drug administration.
   * Subject is age of 24 months or less with a current hemodynamically significant congenital heart disease at the start of study drug administration.
2. Subject requires oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure or other mechanical respiratory or cardiac support at Screening and at the start of study drug administration.
3. Subject has a current active infection including respiratory syncytial virus infection at Screening and at the start of study drug administration.
4. Subject has a serious concurrent medical condition (hepatic dysfunction, persistent seizure disorder, etc.) except those resulting in an immune deficiency condition or renal failure.
5. Subject has received palivizumab prior to the study drug administration.
6. Subject has received any other investigational agents in the past 3 months or 5 half lives prior to the investigational drug administration (whichever is longer).
7. Subject has a history of an allergic reaction or hypersensitivity to constituents of the study drug.
8. Subject has a history of serious adverse reactions or serious allergic reaction to immunoglobulin products or has a history of hypersensitivity to immunoglobulin products, blood products, or other foreign proteins.
9. Subject whose remaining days of life are expected to be less than one year at the time of informed consent.
10. It will be impossible to collect blood as scheduled from the subject.
11. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Participant flow

Outcome results

• Serum Palivizumab Trough Concentrations at Day 1, Day 31, and Day 121 (Primary), Mean, µg/mL: Palivizumab 0 +/- 0
• Percentage of Participants Requiring Hospitalization For Respiratory Syncytial Virus (RSV) Infection (Secondary), Number, percentage of participants: Palivizumab 0 (0.0 to 12.3)
• Percentage of Participants Who Required Treatment for Respiratory Syncytial Virus (RSV) Infection (Secondary), Number, percentage of participants: Palivizumab 0 (0.0 to 12.3)
• Duration of Hospitalization Caused by Respiratory Syncytial Virus (RSV) Infection (Secondary)
• Duration of Required Treatment for Respiratory Syncytial Virus (RSV) Infection (Secondary)
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs (Secondary), Number, participants: Palivizumab 27
• Mean Baseline and Mean Change From Baseline in Systolic/Diastolic Blood Pressure at Day 121 (Secondary), Mean, mm Hg: Palivizumab 96.1 +/- 9.44
• Mean Baseline and Mean Change From Baseline in Body Temperature at Day 121 (Secondary), Mean, degrees Celcius: Palivizumab 36.77 +/- 0.346
• Mean Baseline and Mean Change From Baseline in Respiratory Rate at Day 121 (Secondary), Mean, respirations per minute: Palivizumab 33.4 +/- 8.59
• Mean Baseline and Mean Change From Baseline in Pulse Rate at Day 121 (Secondary), Mean, beats per minute: Palivizumab 126.6 +/- 21.91
• Mean Baseline and Mean Change From Baseline in Body Weight at Day 121 (Secondary), Mean, kilograms: Palivizumab 8.76 +/- 1.90
• Hematology: Mean Baseline and Mean Change From Baseline in Hemoglobin at Day 121 (Secondary), Mean, g/dL: Palivizumab 11.57 +/- 1.56
• Hematology: Mean Baseline and Mean Change From Baseline in Hematocrit at Day 121 (Secondary), Mean, percentage of red blood cells: Palivizumab 34.32 +/- 4.72
• Hematology: Mean Baseline and Mean Change From Baseline in White Blood Cells (WBC), Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes at Day 121 (Secondary), Mean, cells *10^3/µL: Palivizumab 6.74 +/- 3.93
• Hematology: Mean Baseline and Mean Change From Baseline in Red Blood Cells (RBC) and Platelet Count at Day 121 (Secondary), Mean, cells *10^4/µL: Palivizumab 410.6 +/- 70.83
• Blood Chemistry: Mean Baseline and Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) at Day 121 (Secondary), Mean, U/L: Palivizumab 943.0 +/- 519.10
• Blood Chemistry: Mean Baseline and Change From Baseline in Total Bilirubin, Blood Urea Nitrogen (BUN), Creatinine, and C-reactive Protein (CRP) at Day 121 (Secondary), Mean, mg/dL: Palivizumab 0.30 +/- 0.14
• Urinalysis: Presence of Urine Protein, Glucose, and Occult Blood at Screening and Day 121 (Secondary), Number, participants: Palivizumab 21

Adverse events

Time frame: AEs:from time of initial study drug administration (Day 1) to 100 days after final administration of the study drug. SAEs:from screening period until 100 days after final administration of study drug. Mean (SD) duration of treatment was 183 (37.29) days.

Serious adverse events by term

Other adverse events by term

15 more terms not shown.

• Shigeki Hashimoto, PhD, Study director, AbbVie