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
Overview
- Phase
- Phase 3
- Intervention
- Suptavumab 30 mg/kg
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 1177
- Locations
- 2
- Primary Endpoint
- Part A: Serum Concentration of Suptavumab Over Time
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Part A: Suptavumab 30 mg/kg
Intervention: Suptavumab 30 mg/kg
Part B: Placebo Matched to Suptavumab
Intervention: Placebo Matched to Suptavumab
Part B: Suptavumab 30 mg/kg- 1 Dose
Intervention: Suptavumab 30 mg/kg- 1 Dose
Part B: Suptavumab 30 mg/kg - 2 Doses
Intervention: Suptavumab 30 mg/kg - 2 Doses
Outcomes
Primary Outcomes
Part A: Serum Concentration of Suptavumab Over Time
Time Frame: Day 1 through Day 150
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.
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
Time Frame: From first study drug administration 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.
Secondary Outcomes
- Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline through Day 150)
- Part B: Number of Participants With At Least One Positive Anti-Drug Antibody (ADA) Assay(Day 1 through Day 150)
- Part B: Serum Concentration of Suptavumab(Day 29, 57, 85, 113 and Day 150 Post-dose)
- 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(From the first study drug administration up to Day 150)