Clinical trial NCT00508651: A Phase 1/2A Study to Evaluate the Safety, Immunogenicity, and Shedding of MEDI-560 in Infants 1 to < 12 Months of Age
Official title: An Expanded Phase1/2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Viral Shedding of MEDI-560, A Live, Attenuated Recombinant Parainfluenza Virus Type 3 (PIV3) Vaccine, Administered Intranasally to Healthy Infants 1 to <12 Mos. of Age
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: parainfluenza virus, children, vaccine
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2007-07-30
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of this study is to describe the safety and tolerability of 3 doses of MEDI-560 at 10\^5 TCID50 when administered to children 6 to \< 12 months of age who are HPIV3 (human parainfluenza virus type 3) seronegative at baseline and to infants 1 to \< 3 months of age regardless of baseline serostatus.

Detailed description: This is a randomized, double-blind, placebo-controlled, multidose Phase 1/2a multicenter study designed to evaluate the safety, tolerability, viral shedding, immunogenicity, and genotypic and phenotypic stability of MEDI-560 in infants 1 to \< 12 months of age. Three doses of MEDI-560 at a dosage level of 10\^5 TCID50 were administered 0, 2, and 4 months after enrollment to a 30-participant cohort of 6 to \< 12 month-old HPIV3 seronegative children randomized 2:1 to MEDI-560 vs placebo. A second 160-participant cohort of 1 to \< 3 month-old infants not screened for baseline serostatus was planned but was not opened to enrollment for reasons other than safety. Participants were followed for safety through 180 days post last dose. Nasal wash specimens were collected at screening and Days 7, 12, and 28 following each dose and during unscheduled illness visits to assess vaccine virus shedding and genotypic and phenotypic stability of any shed vaccine virus. Blood was collected at screening to determine eligibility and prior to Dose 1 for baseline serostatus. Blood for assessment of antibodies to HPIV3 was collected approximately 7 to 12 days after Dose 1 and Dose 3 and 1 month after each dose for antibodies to PIV3.

Eligibility criteria: Inclusion Criteria:

1. Male or female whose age on the day of randomization falls within one of the two age cohorts:

   Cohort 1: 6 to \< 12 months (≥ 6 months of age and not yet reached their 1st year birthday); Cohort 2: 1 to \< 3 months (\> 28 days of age and not yet reached their 3rd month birthday)
2. Cohort 1 only: Participant is seronegative to HPIV3 at screening as determined by ELISA; or the legal representative is willing to provide access to data documenting that the participant was screened for another MedImmune trial after written informed consent was obtained, and that the participant is seronegative to HPIV3 within 21 days prior to randomization into MI-CP150 as determined by ELISA at MedImmune
3. Participant was the product of a normal full term pregnancy, defined as 36-42 weeks gestation
4. Participant is in general good health
5. Participant's legal representative is available by telephone
6. Written informed consent and Health Insurance Portability and Accountability Act authorization (if applicable) obtained from the participant's legal representative
7. Participant's legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator
8. Participant is available to complete the follow-up period of 180 days after the final dose of investigational product as required by the protocol
9. Participant'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:

1. Any fever (≥ 100.4°F \[≥ 38.0°C\], regardless of route) or lower respiratory illness within 7 days prior to randomization
2. Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of investigational product
3. Cohort 1 only: weight \< the fifth percentile for age on the day of randomization
4. Cohort 2 only: history of low birth-weight (ie, \< 2,500 grams at birth) or weight \< fifth percentile for age on the day of randomization
5. 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 investigational product dosing, except that infrequent use of over-the-counter medications such as pain relievers are permitted according to the judgment of the investigator
6. Any current or expected receipt of immunosuppressive agents including steroids (≥ 2 mg/kg per day of prednisone or its equivalent, or ≥ 20 mg/day if the participant weighs \>10 kg, given daily or on alternate days for ≥ 14 days); children in this category should not receive investigational product 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
7. History of receipt of blood transfusion or expected receipt through 30 days after final investigational product dosing
8. History of receipt of immunoglobulin products or expected receipt through 30 days after final investigational product dosing
9. Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 30 days after final investigational product dosing
10. Receipt of any live virus vaccine (excluding rotavirus vaccine) within 28 days prior to randomization or expected receipt within a 28-day window around any dose
11. Receipt of any inactivated (eg, non-live) vaccine or rotavirus vaccine within 14 days prior to randomization or expected receipt within a 14-day window around any dose
12. Known or suspected immunodeficiency, including human immunodeficiency virus
13. Living in the same home or enrolled in the same classroom at day care with infants \< 24 months of age within 28 days after each dose (only one child per household may be enrolled into the study)
14. Contact with pregnant caregiver within 28 days after each dose
15. Household contact with an immunocompromised person within 28 days after each dose; the participant should also avoid close contact with immunocompromised individuals for at least 28 days after each investigational product dose
16. Household contact within 28 days after each dose with a healthcare worker who has direct patient care responsibilities or household contact within 28 days after each dose with someone who is a day care provider or preschool teacher for children \< 24 months of age
17. History of allergic reaction to any component of the investigational product
18. Previous medical history or evidence of an intercurrent or chronic illness that, in the opinion of the investigator, may compromise the safety of the participant
19. Known or suspected active or chronic hepatitis infection
20. History of medical diagnosis of asthma, reactive airway disease, wheezing requiring medication, bronchoconstriction or treatment with a β2 agonist (eg, albuterol), cystic fibrosis, chronic lung disease of prematurity (eg, bronchopulmonary dysplasia), chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation
21. A family member or a household contact who is an employee of the research center or otherwise involved with the conduct of the study
22. Any condition that, in the opinion of the investigator, might interfere with investigational product evaluation

Primary outcomes:
measure: Number of Participants With Solicited Adverse Events (SEs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With SEs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With SEs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Adverse Events (AEs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With AEs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With AEs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Medically Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With MA-LRIs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With MA-LRIs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Serious Adverse Events (SAEs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With SAEs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With SAEs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Significant New Medical Conditions (SNMCs)
timeFrame: Day 0 through 180 days after final dose
Secondary outcomes:
measure: Number of Participants Shedding Vaccine-like Virus at Any Time During Study Participation
timeFrame: Days 7, 12, and 28 after each dose and during visits for pre-specified illness symptoms occurring Day 0 through 180 days post final dose.
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 1
timeFrame: Days 7-10 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 1
timeFrame: Days 12-18 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 1
timeFrame: Days 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 1
timeFrame: Days 0-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 2
timeFrame: Days 7-10 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 2
timeFrame: Days 12-18 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 2
timeFrame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 2
timeFrame: Days 0-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 3
timeFrame: Days 7-10 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 3
timeFrame: Days 12-18 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 3
timeFrame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 3.
timeFrame: Days 0-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Hemagglutination Inhibition (HAI) Seroconversion/Seroresponse to HPIV3 28 Days After Dose 1
timeFrame: Days 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 28 Days After Dose 2
timeFrame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 28 Days After Dose 3
timeFrame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Nasal Wash Samples Containing Vaccine-like Virus in the Absence of Admixture With Wild-type HPIV3 in Which the Vaccine-like Virus Was Genotypically Stable
timeFrame: Day 0 after Dose 1 to 180 days after the final dose
measure: Number of Nasal Wash Samples Containing Vaccine-like Virus in the Absence of Admixture With Wild-type HPIV3 in Which the Vaccine-like Virus Was Phenotypically Stable
timeFrame: Day 0 after Dose 1 to 180 days after the final dose
measure: Geometric Mean Titers (GMTs) of Serum HAI Antibodies to HPIV3 at Baseline
timeFrame: Baseline (Day 0 prior to Dose 1)
measure: Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 1
timeFrame: Day 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 2
timeFrame: Day 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 3
timeFrame: Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Children's Investigational Research Program
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Pediatric Clinic
state: Arkansas
city: Madera
country: United States
facility: Madera Family Medical Group
state: California
city: Roseville
country: United States
facility: Allergy Medical Group of the North Area
state: California
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Naranja
country: United States
facility: Homestead Clinical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida College of Medicine Department of Pediatrics
state: Florida
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Lexington
country: United States
facility: Michael W. Simon, M.D.
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
city: Omaha
country: United States
facility: Meridian Clinical Research LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Children's Lung Specialists Ltd.
state: Nevada
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke Health Center- Pickett Road
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma State University Center for Health Sciences
state: Oklahoma
city: Bethlehem
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Belleview Pediactric Assoc.
state: Pennsylvania
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: St. George
country: United States
facility: Dixie Pediatrics
state: Utah
city: Huntington
country: United States
facility: University Physicians Internal Medicine
state: West Virginia
Study officials:
affiliation: MedImmune LLC
name: Judith Falloon, MD
role: STUDY_DIRECTOR
References:
citation: Bernstein DI, Falloon J, Yi T. A randomized, double-blind, placebo-controlled, phase 1/2a study of the safety and immunogenicity of a live, attenuated human parainfluenza virus type 3 vaccine in healthy infants. Vaccine. 2011 Sep 16;29(40):7042-8. doi: 10.1016/j.vaccine.2011.07.031. Epub 2011 Jul 22.