A Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to <24 Month-old Children and in 2 Month-old Infants

Healthy Clinical Trial

Official title:

A Phase 1/2a, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, a Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to < 24 Month-old Children and in 2 Month-old Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00686075
• Other study ID #: MI-CP178
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 23, 2008
• Last updated: September 22, 2014
• Start date: June 2008
• Est. completion date: August 2012

Study information

• Verified date: September 2014
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 in children 6 to less than (<) 24 months of age and in infants 2 months of age.

Description:

This is a Phase 1/2a, randomized, double-blind, placebo-controlled, dose-escalation, multicenter study to evaluate the safety and tolerability of multiple doses of MEDI-534 at 10^5 or 10^6 median tissue culture infectious dose (TCID50) in RSV and PIV3 seronegative children 6 to <24 months of age and at dosages of 10^4, 10^5 or 10^6 TCID50 in unscreened infants 2 months of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1338
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Months to 23 Months

Eligibility

Inclusion Criteria:

• Male or female whose age on the day of randomization falls within one of the two age groups:

6 to less than (<) 24 months (more than [>] 6 months of age and not yet reached their 2nd year birthday), Cohorts 1 and 2 2 months (+/- 4 weeks), Cohorts 3, 4, and 5

• Cohorts 1 and 2 only: Subject is seronegative to both Respiratory Syncytial Virus (RSV) and human Parainfluenza Virus Type 3 (hPIV3) at Screening

• Subject whose gestational age was greater than or equal to (>=) 36 weeks

• Subject is in general good health with normal growth (that is, body weight greater than (>) third percentile per world health organization [WHO] simplified weight-per-age field tables

• Subject's legal representative is available by telephone

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization (if applicable) obtained from the subject's legal representative

• Subject's legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator

• Subject is available to complete the follow-up period 1-year after receipt of the first dose of study vaccine

• Subject's legal representative must be 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 degrees Fahrenheit [>=38.0 degrees Celsius], regardless of route) or lower respiratory illness within 7 days prior to randomization

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

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

• Any drug therapy (chronic or other) within 7 days prior to randomization or expected receipt through the protocol-specified blood collection 28 days after each study vaccine dosing, except that infrequent use of over-the-counter medications for the systemic treatment of common childhood symptoms (that is, pain relievers, decongestants or cough suppressants) are permitted according to the judgment of the investigator

• Any current or expected receipt of immunosuppressive agents including steroids (>=2 milligram per kilogram [mg/kg] per day of prednisone or its equivalent, or >=20 milligram per day [mg/day] if the subject weighs >10 kilogram [kg], given daily or on alternate days for >=14 days); children in this category should not receive study vaccine until immunosuppressive agents including corticosteroid therapy have been discontinued for >=30 days; the use of topical steroids is permitted according to the judgment of the investigator

• History of receipt of blood transfusion or expected receipt through the protocol-specified blood collection at 28 days after final study dosing

• History of receipt of immunoglobulin products or expected receipt through the protocol-specified blood collection at 28 days after final study dosing

• Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 180 days after final study dosing

• Receipt of any live virus vaccine (excluding oral polio vaccine and rotavirus vaccine) within 28 days prior to randomization or expected receipt within a 28-day window around any study vaccine dose

• Receipt of any inactivated (that is, non-live) vaccine or oral polio vaccine or rotavirus vaccine within 14 days prior to randomization or expected receipt within a 14-day window around any study vaccine dose

• Known or suspected immunodeficiency, including human immunodeficiency virus (HIV) infection

• Expected to be living in the same home or enrolled in the same classroom at day care with infants <6 months within 28 days after each dose

• Living in a household with another child who is concurrently enrolled in a study of a live viral vaccine (including this study)

• Expected contact with a pregnant caregiver within 28 days after each dose

• A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after any study vaccine dose

• Expected household contact within 28 days after each dose with a health care provider for immunocompromised subjects or who is a day care provider for infants under the age of 6 months

• History of allergic reaction to any component of the study vaccine

• Previous medical history, or evidence, of an intercurrent or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject

• Known or suspected active or chronic hepatitis infection

• History of medical diagnosis of asthma, reactive airway disease, wheezing requiring medication, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation for respiratory illness (excludes elective mechanical ventilation during surgery for subjects in Cohorts 1 and 2)

• Family member or household contact who is an employee of the research center or otherwise involved with the conduct of the study

• Any condition that, in the opinion of the investigator, might interfere with study vaccine evaluation.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Biological:
• MEDI-534, Cohort 1
Participants aged 6 to less than (<) 24 months will receive MEDI-534, 10^5 median tissue culture infectious dose (TCID50) by intranasal route at Month 0, 2, and 4.

Other:
• Placebo, Cohort 1
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.

Biological:
• MEDI-534, Cohort 2
Participants aged 6 to <24 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.

Other:
• Placebo, Cohort 2
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.

Biological:
• MEDI-534, Cohort 3
Participants aged 2 months will receive MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.

Other:
• Placebo, Cohort 3
Participants aged 2 months will receive placebo matched to MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.

Biological:
• MEDI-534, Cohort 4
Participants aged 2 months will receive MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.

Other:
• Placebo, Cohort 4
Participants aged 2 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.

Biological:
• MEDI-534, Cohort 5
Participants aged 2 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.

Other:
• Placebo, Cohort 5
Participants aged 2 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.

Locations

Country	Name	City	State
Australia	Research Site	Garran	Australian Capital Territory
Australia	Research Site	Herston	Queensland
Australia	Research Site	North Adelaide	South Australia
Australia	Research Site	Subiaco	Western Australia
Brazil	Research Site	Passo Fundo-RS	Rio Grande do Sul
Brazil	Research Site	Porto alegre - RS
Brazil	Research Site	Porto Alegre/RS
Brazil	Research Site	Ribeirao Preto - SP
Brazil	Research Site	Sao Paulo	SP
Brazil	Research Site	São Paulo
Brazil	Research Site	Sao Paulo - SP
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Saskatoon	Saskatchewan
Finland	Research Site	Helsinki
Finland	Research Site	Jarvenpaa
Finland	Research Site	Kokkola
Finland	Research Site	Kuopio
Finland	Research Site	Lahti
Finland	Research Site	Oulu
Finland	Research Site	Pori
Finland	Research Site	Tampere
Finland	Research Site	Turku
Germany	Research Site	Berlin
Germany	Research Site	Freiburg
Germany	Research Site	Mainz
Israel	Research Site	Netanya
South Africa	Research Site	Belle Ville Cape Town	Western Cape
South Africa	Research Site	Cape Town	Western Cape
South Africa	Research Site	Johannesburg	Gauteng
South Africa	Research Site	Pretoria	Gauteng
Spain	Research Site	Almeria	Andalucia
Spain	Research Site	Almeria	Andalucia
Spain	Research Site	Almeria	Andalucia
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Catarroja	Comunidad Valenciana
Spain	Research Site	Esplugues de Llobregat
Spain	Research Site	Jerez de la Frontera	Andalucía
Spain	Research Site	La Eliana, Valencia	Comunidad Valenciana
Spain	Research Site	Madrid	Madrid, Communidad de
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	San Sebastian	Pais Vasco
Spain	Research Site	Santiago de Compostela	Galicia
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valencia	Comunidad Valenciana
United States	Research Site	Amarillo	Texas
United States	Research Site	Anaheim	California
United States	Research Site	Anaheim	California
United States	Research Site	Bell Gardens	California
United States	Research Site	Bentonville	Arkansas
United States	Research Site	Bridgeton	Missouri
United States	Research Site	Brooklyn	New York
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Dalton	Georgia
United States	Research Site	Downey	California
United States	Research Site	Gainesville	Florida
United States	Research Site	Gresham	Oregon
United States	Research Site	Houston	Texas
United States	Research Site	Huntington	West Virginia
United States	Research Site	Jackson	Tennessee
United States	Research Site	Johnson City	New York
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lake Success	New York
United States	Research Site	Lakewood	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Layton	Utah
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Long Beach	California
United States	Research Site	Midlothian	Virginia
United States	Research Site	Mobile	Alabama
United States	Research Site	New Bern	North Carolina
United States	Research Site	Omaha	Nebraska
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orem	Utah
United States	Research Site	Paducah	Kentucky
United States	Research Site	Paramount	California
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Poteet	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	Sellersville	Pennsylvania
United States	Research Site	Shreveport	Louisiana
United States	Research Site	St. George	Utah
United States	Research Site	St. Paul	Minnesota
United States	Research Site	Stony Brook	New York
United States	Research Site	Syracuse	New York
United States	Research Site	Tampa	Florida
United States	Research Site	Thornton	Colorado
United States	Research Site	Tomball	Texas
United States	Research Site	Topeka	Kansas
United States	Research Site	West Covina	California

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Finland,  Germany,  Israel,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Solicited Symptoms After Dose 1	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever greater than or equal to (>=) 100.4 degrees Fahrenheit (F), runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.	Within 28 days after Dose 1	Yes
Primary	Number of Participants With Solicited Symptoms After Dose 2	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever >=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.	Within 28 days after Dose 2	Yes
Primary	Number of Participants With Solicited Symptoms After Dose 3	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever >=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.	Within 28 days after Dose 3	Yes
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 1	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAEs) for Dose 1 are events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 1 were reported.	Within 28 days after Dose 1	Yes
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 2	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 2 are events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 2 were reported.	Within 28 days after Dose 2	Yes
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 3	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 3 are events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 3 were reported.	Within 28 days after Dose 3	Yes
Primary	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 1	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 1 were reported.	Within 28 days after Dose 1	Yes
Primary	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 2	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 2 were reported.	Within 28 days after Dose 2	Yes
Primary	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 3	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 3 were reported.	Within 28 days after Dose 3	Yes
Primary	Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.	Within 28 days after Dose 1	Yes
Primary	Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 2	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.	Within 28 days after Dose 2	Yes
Primary	Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 3	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.	Within 28 days after Dose 3	Yes
Secondary	Number of Participants Who Shed Vaccine-Type Virus	Nasal wash specimens were collected to assess vaccine virus recovery in the upper respiratory tract on 7, 12 and 28 days after each dosing.	7, 12 and 28 days after Dose 1, 2 and 3	No
Secondary	Percentage of Participants With a Seroresponse to Respiratory Syncytial Virus (RSV) and Human Parainfluenza Virus Type 3 (hPIV3) After Dose 3	Seroresponse was defined as a >=4-fold rise from Baseline in neutralizing antibody titer, regardless of Baseline serostatus. Respiratory Syncytial Virus (RSV) and hPIV3 antibody titers were determined by using microneutralization assay and hemagglutination inhibition assay, respectively. Clopper-pearson exact confidence interval was reported.	Day 28 after Dose 3	No
Secondary	Genotypic Stability of Recovered Vaccine-Type Virus	Nasal wash samples with vaccine-type virus were evaluated for genotypic stability, defined as the presence of the entire RSV-Fusion (RSV F) insert based on the RSV F sequence results. If the insert was absent or truncated, the recovered virus was counted as genotypically unstable. Nasal wash samples were categorized as genotypically stable, genotypically unstable or undetermined genotypic stability.	Within 28 days after any dose	No
Secondary	Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) Through 365 Days After Randomization	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea. MA-LRIs occurring within 28 days post any dose and after 28 days post any dose were summarized separately.	Day 0 to Day 365	Yes
Secondary	Number of Participants With Significant New Medical Conditions (SNMCs) Through 365 Days After Randomization	An SNMC was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of SNMCs include diabetes, asthma, autoimmune disease (for example, lupus, rheumatoid arthritis), and neurological disease (for example, epilepsy, autism).	Day 0 to Day 365	Yes
Secondary	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through 365 Days After Randomization	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events after administration of drug which were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) within 365 days after randomization were reported.	Day 0 to Day 365	Yes

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