A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety of MEDI-559 in Healthy 1 to <24 Month-Old Children

Healthy Clinical Trial

— MEDI-559  

Official title:

A Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Viral Shedding of MEDI-559, a Live Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus in Healthy 1 to <24 Month-Old Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00767416
• Other study ID #: MI-CP147
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 3, 2008
• Last updated: July 18, 2016
• Start date: October 2008
• Est. completion date: December 2011

Study information

• Verified date: July 2016
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 1 to <24 months of age.

Description:

This is a randomized, double-blind, placebo-controlled, multi-dose, Phase 1/2a multi-center trial to evaluate the safety, tolerability, viral shedding, immunogenicity, and genotypic and phenotypic stability of MEDI-559 in RSV seronegative infants 5 to <24 months of age and in infants 1 to <3 months of age regardless of baseline serostatus. The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 5 to <24 months of age and to healthy infants 1 to <3 months of age regardless of baseline serostatus.

MEDI-559 will be administered at a dose of 10^5 fluorescent focus units (FFU) on a 0, 2, and 4 month schedule to two cohorts of subjects in a step-wise fashion. The target sample size for this study is 320 subjects, with 160 subjects 5 to <24 months of age enrolled into Cohort 1 and 160 subjects 1 to <3 months of age enrolled into Cohort 2. Each cohort will be randomized 1:1 (MEDI-559 to placebo) and stratified by site. Cohort 1 will initiate dosing at 10^5 FFU MEDI-559. Blinded safety data from the first 40 subjects enrolled in Cohort 1 for the 28 days following administration of the first dose of vaccine will be reviewed. If no safety concerns are noted, Cohort 2 will initiate dosing at 10^5 FFU. Enrollment into Cohort 2 will be halted after approximately 40 subjects have been randomized, and blinded safety data will be reviewed through 28 days post Dose 1. If no safety concerns are noted, the remainder of Cohort 2 will be enrolled. All subjects will be followed through 365 days after randomization to ensure that each subject has been followed through an RSV season.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 1 Month to 23 Months

Eligibility

Inclusion Criteria:

• Male or female whose age on the day of randomization falls within one of the two age cohorts: Cohort 1: 5 to <24 months (reached their 5th month birthday but not yet reached their 2nd year birthday); Cohort 2: 1 to < 3 months (>28 days of age and not yet reached their 3rd month birthday)

• Cohort 1 only: Subject is seronegative to RSV at screening

• Subject was the product of normal full term pregnancy (defined as 36-42 weeks gestation)

• Subject is in general good health

• Written informed consent and HIPAA authorization (if applicable) obtained from the subject's legal representative

• Subject's legal representative is willing and able to bring the subject to the study site for evaluation of respiratory illness in accordance with the protocol

Exclusion Criteria:

• Any fever (= 100.4°F [= 38.0°C]), regardless of route within 7 days prior to randomization

• Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization

• Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of vaccine

• Cohort 1 only: weight = 5th percentile for age on the day of randomization

• Cohort 2 only: history of low birth weight (ie, <2500 grams at birth) or weight = 5th percentile for age on the day of randomization

• Living in the same home or enrolled in the same classroom at day care with infants <6 months of age within 28 days after each dose (only one child per household may be enrolled into the study)

• Contact with pregnant caregiver within 28 days after each dose

• Living in a household with someone who is immunocompromised within 28 days after each dose; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after each study vaccine dosing

• Living in a household with someone who works in the healthcare field and who has direct patient care responsibilities within 28 days after each dose

• Living in a household with someone who is a day care provider or preschool teacher for children <6 months of age within 28 days after each dose

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Biological:
• MEDI-559
Cohort 1 (5 to <24 months): N=80 MEDI-559 at 10^5 FFU at 0, 2, and 4 months; frozen preparation filled into 0.5 ml luer slip-tip syringes. Each 0.2 ml dose contains 10^5 FFU MEDI-559 in a sucrose phosphate glutamate buffer.

Other:
• Placebo
Cohort 1 (5 to < 24 months); N = 80 placebo at 0, 2, and 4 months; frozen preparation filled into 0.5 ml luer slip-tip syringes. Each 0.2 ml dose contains sucrose phosphate buffer.

Locations

Country	Name	City	State
Puerto Rico	Research Site	Caguas
United States	Research Site	Ames	Iowa
United States	Research Site	Anaheim	California
United States	Research Site	Bardstown	Kentucky
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bridgeton	Missouri
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Colonial Heights	Virginia
United States	Research Site	Conway	Arkansas
United States	Research Site	Corpus Christi	Texas
United States	Research Site	Cypress	California
United States	Research Site	Dalton	Georgia
United States	Research Site	Downey	California
United States	Research Site	Endwell	New York
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Fishers	Indiana
United States	Research Site	Franklin	Tennessee
United States	Research Site	Fredrick	Maryland
United States	Research Site	Greenville	Alabama
United States	Research Site	Hartford	Connecticut
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huber Heights	Ohio
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntsville	Alabama
United States	Research Site	Jackson	Tennessee
United States	Research Site	Johnson City	Tennessee
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kingsport	Tennessee
United States	Research Site	Lakewood	California
United States	Research Site	Layton	Utah
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Louisville	Kentucky
United States	Research Site	Metarie	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Midlothian	Virginia
United States	Research Site	Mobile	Alabama
United States	Research Site	New Albany	Indiana
United States	Research Site	Norman	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange City	Florida
United States	Research Site	Paducah	Kentucky
United States	Research Site	Paramount	California
United States	Research Site	Richmond	Virginia
United States	Research Site	San Angelo	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Santa Ana	California
United States	Research Site	South Bend	Indiana
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	St. George	Utah
United States	Research Site	Stony Brook	New York
United States	Research Site	Syracuse	New York
United States	Research Site	Syracuse	Utah
United States	Research Site	Tampa	Florida
United States	Research Site	Thornton	Colorado
United States	Research Site	Tomball	Texas
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Walla Walla	Washington
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of solicited symptoms after Dose 1	Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis	Through Day 28 after each dose	Yes
Primary	Incidence of solicited symptoms after Dose 2	Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis	Through Day 28 after each dose	Yes
Primary	Incidence of solicited symptoms after Dose 3	Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever >100.4°F (>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis	Through Day 28 after each dose	Yes
Primary	Incidence of adverse events (AEs) after Dose 1	As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Through Day 28 after each dose	Yes
Primary	Incidence of AEs after Dose 2	As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Through Day 28 after each dose	Yes
Primary	Incidence of AEs after Dose 3	As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Through Day 28 after each dose	Yes
Primary	Incidence of medically-attended lower respiratory illnesses (MA-LRIs) after Dose 1	An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea	Through Day 28 after each dose	Yes
Primary	Incidence of MA-LRIs after Dose 2	An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea	Through Day 28 after each dose	Yes
Primary	Incidence of MA-LRIs after Dose 3	An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea	Through Day 28 after each dose	Yes
Primary	Incidence of SAEs	An SAE is any adverse event that results in any of the following outcomes: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly/birth defect (in the offspring of a subject); an important medical event that may not result in death, threaten life or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.	Administration of Dose 1 (Day 0) through Day 28 post final dose	Yes
Secondary	Incidence of MEDI-559 shedding	Number (%) of subjects who shed vaccine-type virus	Day 7-10 after Dose 1, 2, and 3	No
Secondary	Incidence of MEDI-559 shedding	Number (%) of subjects who shed vaccine-type virus	Day 12-18 after Dose 1, 2, and 3	No
Secondary	Incidence of MEDI-559 shedding	Number (%) of subjects who shed vaccine-type virus	Day 28-34 post Dose 1, 2, and 3	No
Secondary	Post-vaccination seroresponse against RSV	Seroresponse is defined as a = 4-fold rise from baseline as measured by microneutralization assay	Day 28 post final dose	No
Secondary	Phenotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable	Day 7-10 post any dose	No
Secondary	Phenotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable	Day 12-18 post any dose	No
Secondary	Phenotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable	Day 28-34 post any dose	No
Secondary	Genotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable	Day 7-10 post any dose	No
Secondary	Genotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable	Day 12-18 post any dose	No
Secondary	Genotypic stability of recovered vaccine-type virus	Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable	Day 28-34 post any dose	No
Secondary	Incidence of MA-LRIs	Number (%) of subjects with MA-LRIs occurring from Study Day 0 through the end of study	Study Day 0 through 365 days post randomization	Yes
Secondary	Incidence of SAEs	Number (%) of subjects with SAEs occurring from Study Day 0 through 365 days post randomization	Study Day 0 post Dose 1 through 365 days post randomization	Yes
Secondary	Incidence of significant new medical conditions (SNMCs)	Number (%) of subjects with SNMCs from administration of Dose 1 through 365 days post randomization	Study Day 0 post Dose 1 through 365 days post randomization	Yes

External Links

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•   MEDI-559_CP-147_Protocol_Redacted_13Nov13