A Phase 1/2A Study to Evaluate the Safety, Immunogenicity, and Shedding of MEDI-560 in Infants 1 to < 12 Months of Age

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: MEDI-560
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) 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 Participant was the product of a normal full term pregnancy, defined as 36-42 weeks gestation Participant is in general good health Participant's legal representative is available by telephone Written informed consent and Health Insurance Portability and Accountability Act authorization (if applicable) obtained from the participant's legal representative Participant's legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator Participant is available to complete the follow-up period of 180 days after the final dose of investigational product as required by the protocol 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: Any fever (≥ 100.4°F [≥ 38.0°C], 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 prevent intranasal delivery of investigational product Cohort 1 only: weight < the fifth percentile for age on the day of randomization 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 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 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 History of receipt of blood transfusion or expected receipt through 30 days after final investigational product dosing History of receipt of immunoglobulin products or expected receipt through 30 days after final investigational product dosing Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 30 days after final investigational product dosing 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 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 Known or suspected immunodeficiency, including human immunodeficiency virus 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) Contact with pregnant caregiver within 28 days after each dose 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 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 History of allergic reaction to any component of the investigational product 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 Known or suspected active or chronic hepatitis infection 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 A family member or a 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 investigational product evaluation

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 11 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 MEDI-560<br>MEDI-560 vaccine was a frozen preparation of live, attenuated rHPIV3cp45 virus filled into Becton Dickinson^TM Luer slip tip syringes. Each 0.2 mL dose contained 10^5 TCID50 of MEDI-560 in a sucrose phosphate glutamate buffer. | Biological: MEDI-560<br>* MEDI-560 vaccine was a frozen preparation of live, attenuated rHPIV3cp45 virus filled into Becton Dickinson^TM luer slip tip syringes. Each 0.2 mL dose contained 10^5 TCID50 of MEDI-560 in a sucrose phosphate glutamate buffer.<br>|
| Placebo Comparator: Cohort 1 Placebo<br>Placebo was a frozen preparation filled into Becton Dickinson^TM Luer slip-tip syringes. Each 0.2 mL dose contained sucrose phosphate buffer. | Biological: Placebo<br>* Placebo was a frozen preparation filled into Becton Dickinson^TM luer slip-tip syringes. Each 0.2 mL dose contained sucrose phosphate buffer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Adverse Events (SEs) After Dose 1 |  | Days 0-28 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With SEs After Dose 2 |  | Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With SEs After Dose 3 |  | Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Adverse Events (AEs) After Dose 1 | Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 1. | Days 0-28 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With AEs After Dose 2 | Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 2. | Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With AEs After Dose 3 | Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 3. | Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Medically Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1 |  | Days 0-28 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With MA-LRIs After Dose 2 |  | Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With MA-LRIs After Dose 3 |  | Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Serious Adverse Events (SAEs) After Dose 1 |  | Days 0-28 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With SAEs After Dose 2 | One participant had event of pneumonia after Dose 2. | Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With SAEs After Dose 3 |  | Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Significant New Medical Conditions (SNMCs) | A SNMC is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant. | Day 0 through 180 days after final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Shedding Vaccine-like Virus at Any Time During Study Participation | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | 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. | 
| Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 1 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 7-10 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 1 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 12-18 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 1 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 1 |  | Days 0-34 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 2 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 7-10 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 2 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 12-18 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 2 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 2 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 0-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 3 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 7-10 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 3 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 12-18 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 3 | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 3. | Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified. | Days 0-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Hemagglutination Inhibition (HAI) Seroconversion/Seroresponse to HPIV3 28 Days After Dose 1 | Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid. | Days 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 28 Days After Dose 2 | Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid. | Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 28 Days After Dose 3 | Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid. | Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| 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 | A nasal wash specimen was collected at screening and on Days 7 (7-10), 12 (12-18), and 28 (28-34) post each dose and during visits for pre-specified illness symptoms occurring Day 0 through 180 days post final dose to assess vaccine virus replication. Genotypic stability of recovered vaccine-type virus at the 15 mutations of phenotypic importance was assessed. | Day 0 after Dose 1 to 180 days after the final dose | 
| 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 | A nasal wash specimen was collected at screening and on Days 7 (7-10), 12 (12-18), and 28 (28-34) post each dose and during visits for pre-specified illness symptoms occurring Day 0 through 180 days post final dose to assess vaccine virus replication. Determination of the temperature sensitivity of recovered vaccine-type virus. | Day 0 after Dose 1 to 180 days after the final dose | 
| Geometric Mean Titers (GMTs) of Serum HAI Antibodies to HPIV3 at Baseline | Pre-dose GMT of HAI antibody to HPIV3 | Baseline (Day 0 prior to Dose 1) | 
| Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 1 | Post-Dose 1 GMT of HAI antibody to HPIV3 | Day 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 2 | Post-Dose 2 GMT of HAI antibody to HPIV3 | Day 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Geometric Mean Titers of Serum Antibodies to HPIV3 Day 28 Post Dose 3 | Post-Dose 3 GMT of HAI antibody to HPIV3 | Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parainfluenza virus, children, vaccine