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

Respiratory Syncytial Virus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02325791
• Other study ID #: R2222-RSV-1332
• Status: Completed
• Phase: Phase 3
• Start date: July 21, 2015
• Est. completion date: September 26, 2017

Study information

• Verified date: October 2018
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1177
• Est. completion date: September 26, 2017
• Est. primary completion date: July 5, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 6 Months

Eligibility

Key Inclusion Criteria:

1. 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)

2. Gestational age is =35 weeks, 6 days at birth

3. 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:

1. Eligible, recommended and have access to receive palivizumab per AAP or other local guidelines, standard practice, or by their healthcare provider

2. History of CLD defined as requirement of supplemental oxygen for 28 days after birth

3. Known hemodynamically significant congenital heart disease

4. Known immunodeficiency, neuromuscular disease, or congenital abnormalities of the airway

5. Known renal or hepatic dysfunction

6. Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders

7. Known or suspected impairment of immunological functions or autoimmune diseases

8. History of anaphylaxis

9. Previously received palivizumab or any other investigational RSV prophylaxis or vaccine product

10. Previous reaction to IV immunoglobulin, blood products or other foreign proteins, including vaccines and monoclonal antibodies

Note: Other inclusion and exclusion criteria apply

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Drug:
• Suptavumab 30 mg/kg
Participants received single dose of suptavumab 30 milligram per kilogram (mg/kg) intramuscularly (IM) on Day 1.
• Placebo Matched to Suptavumab
Participants received 2 IM doses of placebo matched to suptavumab: the first dose on Day 1 and the second dose on Day 57.
• Suptavumab 30 mg/kg- 1 Dose
Participants received single dose of suptavumab 30 mg/kg IM on Day 1 and single dose of placebo matched to suptavumab on Day 57.
• Suptavumab 30 mg/kg - 2 Doses
Participants received 2 doses of suptavumab 30 mg/kg IM: the first dose on Day 1 and the second dose on Day 57.

Locations

Country	Name	City	State
Australia	Regeneron Study Site	Hobart	Tasmania
Bulgaria	Regeneron Study Site	Blagoevgrad
Bulgaria	Regeneron Study Site	Dobrich
Bulgaria	Regeneron Study Site	Gabrovo
Bulgaria	Regeneron Study Site	Kazanlak	Stara Zagora
Bulgaria	Regeneron Study Site	Lom
Bulgaria	Regeneron Study Site	Montana
Bulgaria	Regeneron Study Site	Pleven
Bulgaria	Regeneron Study Site	Plovdiv
Bulgaria	Regeneron Study Site	Ruse
Bulgaria	Regeneron Study Site	Silistra
Bulgaria	Regeneron Study Site	Sliven
Bulgaria	Regeneron Study Site	Sofia	Sofia-Grad
Bulgaria	Regeneron Study Site	Vidin
Canada	Regeneron Study Site	Calgary	Alberta
Canada	Regeneron Study Site	Halifax	Nova Scotia
Canada	Regeneron Study Site	Ottawa	Ontario
Chile	Regeneron Study Site	La Florida	Santiago
Chile	Regeneron Study Site	Providencia	Santiago
Chile	Regeneron Study Site	Puente Alto	Santiago
Chile	Regeneron Study Site	Recoleta	Santiago
Chile	Regeneron Study Site	San Jose	Santiago
Chile	Regeneron Study Site	San Ramon	Santiago
Denmark	Regeneron Study Site	Aalborg
Denmark	Regeneron Study Site	Hjorring
Denmark	Regeneron Study Site	Naestved
Denmark	Regeneron Study Site	Viborg
Finland	Regeneron Study Site	Oulu	Oulun Iaani
Finland	Regeneron Study Site	Pori
Finland	Regeneron Study Site	Tampere	Oulun Iaani
Finland	Regeneron Study Site	Turku
Germany	Regeneron Study Site	Bochum
Germany	Regeneron Study Site	Bramsche
Germany	Regeneron Study Site	Bretten
Germany	Regeneron Study Site	Frankenthal
Germany	Regeneron Study Site	Freiburg
Germany	Regeneron Study Site	Hamburg
Germany	Regeneron Study Site	Herxheim
Germany	Regeneron Study Site	Leipzig
Germany	Regeneron Study Site	Mainz
Germany	Regeneron Study Site	Mannheim
Germany	Regeneron Study Site	Moenchengladbach
Germany	Regeneron Study Site	Munich
Germany	Regeneron Study Site	Sankt Augustin
Germany	Regeneron Study Site	Wanzleben
Hungary	Regeneron Study Site	Budapest
Hungary	Regeneron Study Site	Gyula
Hungary	Regeneron Study Site	Nyiregyhaza
Hungary	Regeneron Study Site	Pecs
Hungary	Regeneron Study Site	Szeged	Csongrad
Hungary	Regeneron Study Site	Veszprem
Netherlands	Regeneron Study Site	Utrecht
New Zealand	Regeneron Study Site	Auckland	North Island
New Zealand	Regeneron Study Site	Palmerston North	Manawatu-Wanganui
New Zealand	Regeneron Study Site	Wellington
Panama	Regeneron Study Site	Ciudad de Panama
Puerto Rico	Regeneron Study Site	San Juan
South Africa	Regeneron Study Site	Ga-Rankuwa	North - West
South Africa	Regeneron Study Site	Johannesburg	Gauteng
South Africa	Regeneron Study Site	Pretoria	Gauteng
Spain	Regeneron Study Site	Esplugues de Llobregat	Barcelona
Spain	Regeneron Study Site	Granada
Spain	Regeneron Study Site	La Coruna
Spain	Regeneron Study Site	Madrid
Spain	Regeneron Study Site	Malaga
Spain	Regeneron Study Site	Manises
Spain	Regeneron Study Site	Santiago de Compostela
Spain	Regeneron Study Site	Sevilla
Sweden	Regeneron Study Site	Goteborg
Sweden	Regeneron Study Site	Uppsala
Turkey	Regeneron Study Site	Ankara
Turkey	Regeneron Study Site	Istanbul
Turkey	Regeneron Study Site	Izmir
Turkey	Regeneron Study Site	Kocaeli
Ukraine	Regeneron Study Site	Chernivtsi	Chernivets'ka Oblast'
Ukraine	Regeneron Study Site	Dnipropetrovsk	Dnipropetrovs'ka Oblast'
Ukraine	Regeneron Study Site	Kharkiv
Ukraine	Regeneron Study Site	Kyiv
Ukraine	Regeneron Study Site	Odessa	Odes'ka Oblast'
Ukraine	Regeneron Study Site	Poltava
Ukraine	Regeneron Study Site	Sumy
Ukraine	Regeneron Study Site	Ternopil
Ukraine	Regeneron Study Site	Vinnytsia	Vinnyts'ka Oblast'
Ukraine	Regeneron Study Site	Zaporizhzhia
United Kingdom	Regeneron Study Site	Belfast
United Kingdom	Regeneron Study Site	Birmingham
United Kingdom	Regeneron Study Site	Coventry	Birmingham
United Kingdom	Regeneron Study Site	Gillingham	Kent
United Kingdom	Regeneron Study Site	Glasgow
United Kingdom	Regeneron Study Site	London	London, City Of
United Kingdom	Regeneron Study Site	Manchester
United Kingdom	Regeneron Study Site	Oldham	Manchester
United Kingdom	Regeneron Study Site	Poole
United Kingdom	Regeneron Study Site	Reading
United Kingdom	Regeneron Study Site	Sheffield
United Kingdom	Regeneron Study Site	Southampton	Hampshire
United Kingdom	Regeneron Study Site	Stockport	Manchester
United Kingdom	Regeneron Study Site	Stockton on Tees
United States	Regeneron Study Site	Alcoa	Tennessee
United States	Regeneron Study Site	Allentown	Pennsylvania
United States	Regeneron Study Site	Anaheim	California
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Aurora	Colorado
United States	Regeneron Study Site	Austin	Texas
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Bardstown	Kentucky
United States	Regeneron Study Site	Bell Gardens	California
United States	Regeneron Investigational Site	Birmingham	Alabama
United States	Regeneron Study Site	Boone	North Carolina
United States	Regeneron Study Site	Boynton Beach	Florida
United States	Regeneron Study Site	Bridgeton	Missouri
United States	Regeneron Study Site	Bronx	New York
United States	Regeneron Study Site	Brooklyn	New York
United States	Regeneron Study Site	Chapel Hill	North Carolina
United States	Regeneron Study Site	Charleston	South Carolina
United States	Regeneron Study Site	Charlottesville	Virginia
United States	Regeneron Study Site	Cheraw	South Carolina
United States	Regeneron Study Site	Cincinnati	Ohio
United States	Regeneron Study Site	Cleveland	Ohio
United States	Regeneron Study Site	Columbus	Ohio
United States	Regeneron Study Site	Columbus	Georgia
United States	Regeneron Study Site	Dalton	Georgia
United States	Regeneron Study Site	Dayton	Ohio
United States	Regeneron Study Site	Dinuba	California
United States	Regeneron Study Site	Downey	California
United States	Regeneron Study Site	Duluth	Minnesota
United States	Regeneron Study Site	Durham	North Carolina
United States	Regeneron Study Site	Erie	Pennsylvania
United States	Regeneron Study Site	Fairfield	Ohio
United States	Regeneron Study Site	Fall River	Massachusetts
United States	Regeneron Study Site	Fort Sam Houston	Texas
United States	Regeneron Study Site	Gainesville	Florida
United States	Regeneron Study Site	Greenville	South Carolina
United States	Regeneron Study Site	Gresham	Oregon
United States	Regeneron Study Site	Hartford	Connecticut
United States	Regeneron Study Site	Hermitage	Pennsylvania
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Huntington	West Virginia
United States	Regeneron Study Site	Huntington Beach	California
United States	Regeneron Study Site	Hutchinson	Kansas
United States	Regeneron Study Site	Jackson	Mississippi
United States	Regeneron Study Site	Jacksonville	Florida
United States	Regeneron Study Site	Kansas City	Missouri
United States	Regeneron Study Site	Kingsport	Tennessee
United States	Regeneron Study Site	Kingwood	West Virginia
United States	Regeneron Study Site	La Puente	California
United States	Regeneron Study Site	Layton	Utah
United States	Regeneron Study Site	Lebanon	New Hampshire
United States	Regeneron Study Site	Lincoln	Nebraska
United States	Regeneron Study Site	Little Rock	Arkansas
United States	Regeneron Study Site	Los Angeles	California
United States	Regeneron Study Site	Louisville	Kentucky
United States	Regeneron Study Site	Madera	California
United States	Regeneron Study Site	Madison	Wisconsin
United States	Regeneron Study Site	Marshfield	Wisconsin
United States	Regeneron Study Site	Mayfield Heights	Ohio
United States	Regeneron Study Site	Meridian	Idaho
United States	Regeneron Study Site	Metairie	Louisiana
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Midlothian	Virginia
United States	Regeneron Study Site	Milwaukee	Wisconsin
United States	Regeneron Study Site	Mineola	New York
United States	Regeneron Study Site	Minneapolis	Minnesota
United States	Regeneron Study Site	Mobile	Alabama
United States	Regeneron Study Site	Morgantown	West Virginia
United States	Regeneron Study Site	Nampa	Idaho
United States	Regeneron Study Site	Nashville	Tennessee
United States	Regeneron Study Site	Neptune	New Jersey
United States	Regeneron Study Site	New Brunswick	New Jersey
United States	Regeneron Study Site	New Hyde Park	New York
United States	Regeneron Study Site	New Orleans	Louisiana
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Norfolk	Nebraska
United States	Regeneron Study Site	North Charleston	South Carolina
United States	Regeneron Study Site	Oklahoma City	Oklahoma
United States	Regeneron Study Site	Omaha	Nebraska
United States	Regeneron Study Site	Orlando	Florida
United States	Regeneron Study Site	Palmdale	California
United States	Regeneron Study Site	Pensacola	Florida
United States	Regeneron Study Site	Peoria	Illinois
United States	Regeneron Study Site	Raleigh	North Carolina
United States	Regeneron Study Site	Reno	Nevada
United States	Regeneron Study Site	Richmond	Virginia
United States	Regeneron Study Site	Rochester	New York
United States	Regeneron Study Site	Roy	Utah
United States	Regeneron Study Site	Saint George	Utah
United States	Regeneron Study Site	Saint Paul	Minnesota
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	Shreveport	Louisiana
United States	Regeneron Study Site	Silver Spring	Maryland
United States	Regeneron Study Site	South Bend	Indiana
United States	Regeneron Study Site	Stevensville	Michigan
United States	Regeneron Study Site	Syracuse	New York
United States	Regeneron Study Site	Syracuse	Utah
United States	Regeneron Study Site	Tampa	Florida
United States	Regeneron Study Site	Thornton	Colorado
United States	Regeneron Study Site	Toledo	Ohio
United States	Regeneron Study Site	Topeka	Kansas
United States	Regeneron Study Site	Tulsa	Oklahoma
United States	Regeneron Study Site	Ventura	California
United States	Regeneron Study Site	Vienna	Virginia
United States	Regeneron Study Site	West Covina	California
United States	Regeneron Study Site	Winter Park	Florida
United States	Regeneron Study Site	Woburn	Massachusetts
United States	Regeneron Study Site	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Chile,  Denmark,  Finland,  Germany,  Hungary,  Netherlands,  New Zealand,  Panama,  Puerto Rico,  South Africa,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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