Study to Evaluate the Efficacy and Safety of Suptavumab (REGN2222) for the Prevention of Medically Attended RSV (Respiratory Syncytial Virus) Infection in Preterm Infants

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of suptavumab (REGN2222) in infants born no more than 35 weeks, 6 days gestational age who are no more than 6 months of age at the time of enrollment in their respective geographic location. In order to optimize the potential benefit in this vulnerable population, we conducted this study during the RSV season using dosing regimens that are expected to be effective.

Detailed Description
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This study occurred in two parts: Part A and Part B. Part A of the study was an open-label, PK evaluation of intramuscular (IM) administered suptavumab in preterm infants for whom palivizumab was not recommended to enable the selection of dosing regimens for Part B. Part B of the study was randomized, double-blind, and placebo-controlled, designed to evaluate efficacy, safety, serum concentration and immunogenicity of IM administration of suptavumab in preterm infants for whom palivizumab was not recommended. The total duration of Part B was up to 265 days (includes a 28-day screening period, 57-day treatment period and 180-day follow-up period). Up to 1515 subjects were planned to be included in Part B of the study. Participants were randomly assigned to 1 of 3 different groups, each with 505 infants; one group received one dose of suptavumab and one dose of placebo, the second group received two doses of suptavumab, and the third group received two doses of placebo. There was a separate genetic testing sub study.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of a Human Monoclonal Antibody, REGN2222, for the Prevention of Medically Attended RSV Infection in Preterm Infants

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: Suptavumab 30 mg/kg
* Drug: Placebo Matched to Suptavumab
* Drug: Suptavumab 30 mg/kg- 1 Dose
* Drug: Suptavumab 30 mg/kg - 2 Doses


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Preterm, otherwise healthy male or female infant who is ≤6 months of age at the time of the first dose (i.e., infant must be treated on or before their 6 month birthday) Gestational age is ≤35 weeks, 6 days at birth Parent(s) or legal guardian(s) of the infant is able to understand the study requirements and willing to provide informed consent Key Exclusion Criteria: Eligible, recommended and have access to receive palivizumab per AAP or other local guidelines, standard practice, or by their healthcare provider History of CLD defined as requirement of supplemental oxygen for 28 days after birth Known hemodynamically significant congenital heart disease Known immunodeficiency, neuromuscular disease, or congenital abnormalities of the airway Known renal or hepatic dysfunction Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders Known or suspected impairment of immunological functions or autoimmune diseases History of anaphylaxis Previously received palivizumab or any other investigational RSV prophylaxis or vaccine product Previous reaction to IV immunoglobulin, blood products or other foreign proteins, including vaccines and monoclonal antibodies Note: Other inclusion and exclusion criteria apply

Ages Eligible for Study
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Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Suptavumab 30 mg/kg<br> | Drug: Suptavumab 30 mg/kg<br>* Participants received single dose of suptavumab 30 milligram per kilogram (mg/kg) intramuscularly (IM) on Day 1.<br>* Other names: REGN2222;|
| Experimental: Part B: Placebo Matched to Suptavumab<br> | Drug: Placebo Matched to Suptavumab<br>* Participants received 2 IM doses of placebo matched to suptavumab: the first dose on Day 1 and the second dose on Day 57.<br>|
| Experimental: Part B: Suptavumab 30 mg/kg- 1 Dose<br> | Drug: Suptavumab 30 mg/kg- 1 Dose<br>* Participants received single dose of suptavumab 30 mg/kg IM on Day 1 and single dose of placebo matched to suptavumab on Day 57.<br>|
| Experimental: Part B: Suptavumab 30 mg/kg - 2 Doses<br> | Drug: Suptavumab 30 mg/kg - 2 Doses<br>* Participants received 2 doses of suptavumab 30 mg/kg IM: the first dose on Day 1 and the second dose on Day 57.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Serum Concentration of Suptavumab Over Time | Part A was primarily designed to determine the pharmacokinetics (PK) of suptavumab in infants to inform the dose regimen used in Part B of the study. The study protocol specified the process and criteria for assessment of the dose. The dose used in Part B was to remain the same as Part A if the PK data up to Day 57 demonstrated that the individual PK observations were consistent with model-predicted concentrations, following age and body weight corrections. | Day 1 through Day 150 | 
| Part B: Percentage of Participants With Medically Attended Respiratory Syncytial Virus (RSV) Infection (Hospitalization or Outpatient Visit With Lower Respiratory Tract Infection [LRTI]) Up to Day 150 | A medically attended RSV infection defined as an infant with positive RSV test by Reverse-transcriptase polymerase chain reaction (RT-PCR) with any of following events: Hospitalized (on basis of assessment of admitting physician) for RSV infection or outpatient visit (emergency room [ER], urgent care [UC], or pediatric clinic visits [for either a sick or well visit]) with RSV lower respiratory tract infection (LRTI). An RSV LRTI in an infant: RSV proven respiratory infection (i.e positive RSV RT-PCR test) with parent(s)/guardian(s) report of cough/difficulty breathing, & with 1 of following signs of LRTI, as assessed by healthcare provider: - lower chest wall in drawing -hypoxemia (peripheral capillary oxygen saturation <95% breathing room air) - Wheezing/crackles. The 150-day efficacy assessment period: first study drug intake through the Day 150 visit. | From first study drug administration up to Day 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any untoward medical occurrence in participants, who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed/worsened/became serious during on-treatment period (defined as time between the date of first study drug administration & date of end of study/last visit).Serious AE: Any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious & non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 4.03(Grade 3 [severe] & Grade 4[life-threatening]) was used in this study to grade clinical AEs. | Baseline through Day 150 | 
| Part B: Serum Concentration of Suptavumab | Serum samples for drug concentration will be collected at pre-specified time points | Day 29, 57, 85, 113 and Day 150 Post-dose | 
| Part B: Number of Participants With At Least One Positive Anti-Drug Antibody (ADA) Assay | ADA category of each participant was classified as pre-existing immunoreactivity (a positive ADA response at baseline with a <4-fold increase in titer for all post baseline samples), treatment-boosted (a positive response at baseline with at least one post baseline titer at >=4-fold the baseline titer), or treatment-emergent (TE [any positive post baseline assay response when baseline results were negative or missing]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 12-week post baseline period [based on nominal sampling time], with no ADA-negative samples in-between, regardless of any missing samples or a positive response at the last ADA sampling time point), indeterminate (a positive assay response at the last collection time point only, regardless of any missing samples), or transient (not persistent/indeterminate, regardless of any missing samples). | Day 1 through Day 150 | 
| Part B: Percentage of Participants Hospitalized With Medically Attended RSV Infection or Outpatient Visit Lower Respiratory Tract Infection (LRTI) or Upper Respiratory Tract Infection (URTI) Up to Day 150 | A medically attended RSV infection was defined as an infant with a positive RSV test by RT-PCR with any of the following events: -Hospitalized (on the basis of the assessment of the admitting physician) for RSV infection - or Outpatient visit (ER, UC), or pediatric clinic visits [for either a sick or well visit]) with RSV LRTI. An RSV LRTI in an infant: RSV-proven respiratory infection (i.e, positive RSV RT-PCR test) with parent(s)/guardian(s) report of cough or difficulty breathing, and with 1 of the following signs of LRTI, as assessed by a healthcare provider: -Lower chest wall indrawing -Hypoxemia (peripheral capillary oxygen saturation <95% breathing room air) -Wheezing or crackles. The 150-day efficacy assessment period:first study drug intake through the Day 150 visit. | From the first study drug administration up to Day 150 |