Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2/3 Randomized, Double-blind, Palivizumab-controlled Study to Evaluate the Safety of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in High-risk Children (MEDLEY)
Brief Summary: The purpose of this study is to evaluate the safety and tolerability of MEDI8897 compared to palivizumab when administered to preterm infants entering their first RSV season and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV season.


Options:
A: Key Inclusion Criteria:

* Healthy infants in their first year of life and born at or after 35 weeks 0 days GA
* Infants who are entering their first RSV season at the time of screening

Key Exclusion Criteria:

* Meets national or other local criteria to receive commercial palivizumab
* Any fever (≥ 100.4°F \[≥ 38.0°C\], regardless of route) or acute illness within 7 days prior to randomization
* Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection
* Receipt of palivizumab or other RSV monoclonal antibody or any RSV vaccine, including maternal RSV vaccination
B: Inclusion Criteria:

* Infants ≤ 3 months-old, presenting to the main pediatric ER with acute bronchiolitis associated with positive RSV rapid antigen test.

Exclusion Criteria:

* Patients will be excluded from the study if they had 1 or more of the following characteristics:

  * Received monoclonal antibody or IVIG within the last 3 months prior to randomization.
  * Receipt of steroids within 2 days before randomization.
  * Hypersensitivity to monoclonal antibodies or immunoglobulin products.
  * Immunodeficiency.
  * Suspected sepsis.
  * Seizure disorders.
  * Neuromuscular disorders.
  * Congenital heart disease.
  * Major congenital anomalies of respiratory tract.
C: Inclusion 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:

   1. Uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, or
   2. Aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone
2. For the CLD/CHD cohort:

   1. 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
   2. 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

Exclusion criteria

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
D: Inclusion Criteria - Maternal Participants:

* Healthy women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications.
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Receiving prenatal standard of care based on country requirements.
* Had a fetal anomaly ultrasound examination performed at ≥18 weeks of pregnancy with no significant fetal abnormalities observed.
* Determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study.
* Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) surface antigen test during this pregnancy and prior to randomization (Visit 1).
* Intention to deliver at a hospital or birthing facility where study procedures can be obtained.
* Expected to be available for the duration of the study and can be contacted by telephone during study participation.
* Participant is willing to give informed consent for her infant to participate in the study.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol OR If the maternal participant is illiterate, a thumbprinted informed consent must be obtained, which must be signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant has been informed of all pertinent aspects of the study.

Inclusion Criteria -Infant Participants:

* Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR If the infant participant's maternal participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted informed consent must have been obtained, which must have been signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant/parent(s)/legal guardian(s) has been informed of all pertinent aspects of the study for herself (maternal participant) and her fetus/infant prior to taking part in the study.
* Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria - Maternal Participants:

* Prepregnancy body mass index (BMI) of \>40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.
* Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
* History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product or any related vaccine.
* Current pregnancy resulting from in vitro fertilization.
* Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:

  * Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
  * Placental abnormality.
  * Polyhydramnios or oligohydramnios.
  * Significant bleeding or blood clotting disorder.
  * Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
  * Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
* Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:

  * Prior preterm delivery ≤34 weeks' gestation.
  * Prior stillbirth or neonatal death.
  * Previous infant with a known genetic disorder or significant congenital anomaly.
* Major illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's participation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (includes positive serologic testing for regional endemic conditions assessed during routine maternal care, as per local standards of care and obstetric recommendations).
* Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including monoclonal antibodies, within the year prior to enrollment.
* Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
* Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study participation.
* Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for \>14 days within 28 days prior to study enrollment. Permitted treatments include the receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, prednisone doses of \<20 mg/day for ≤14 days and, inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids.
* Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when elicited in participant screening, though it may be considered illicit in some locales.
* Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or planned receipt through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
* Previous vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID-19 vaccines or COVID-19 vaccines authorized for temporary or emergency use will not be prohibited during the course of this study.
* Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
* Participants who are breastfeeding at the time of enrollment.

Exclusion Criteria -Infant Participants:

o Infant who is a direct descendant (eg, child or grandchild) of the study personnel.

Answer: C