Safety and Tolerability Study to Evaluate MEDI-534 in Children 6 to < 24 Months of Age

Study Overview
=================
Brief Summary
-----------------
The overall objective of the MEDI-534 clinical development program is to evaluate the safety, efficacy and tolerability of MEDI-534 for the prevention of serious RSV and PIV3 disease in young infants.

Detailed Description
-----------------
The primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 at 10^4, 10^5, or 10^6 TCID50 when administered to RSV and PIV3 seronegative children 6 to <24 months of age.

Official Title
-----------------
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability,Immunogenicity, and Viral Shedding of MEDI-534, a Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV), in Healthy Children 6 to <24 Months of Age

Conditions
-----------------
Respiratory Viral Infections, Respiratory Syncytial Virus Infections, Parainfluenza Virus 3, Human

Intervention / Treatment
-----------------
* Biological: MEDI-534
* Biological: MEDI-534
* Biological: MEDI-534


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female whose age on the day of randomization is 6 to <24 months (reached 6th month birthday and not yet reached 2nd year birthday) Subject is seronegative to both RSV and PIV3 at screening Subject was the product of normal full term pregnancy (defined as >36 weeks gestation) Subject is in general good health Subject's legal representative is available by telephone Written informed consent and 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, which will be through the end of RSV season (provisionally defined as 01/Apr for the United States) or 180 days after the final dose of study vaccine, whichever is later 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 (equal to or greater than 100.4°F [equal to or greater than 38.0°C], regardless of route) or lower respiratory illness (Section 4.1.2) within 7 days prior to randomization Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of vaccine 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 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 equal to or greater than 20 mg/day if the subject weighs >10 kg, given daily or on alternate days for equal to or greater than 14 days); children in this category should not receive study vaccine until immunosuppressive agents including corticosteroid therapy have been discontinued for equal to or greater than 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 following final study vaccine dosing History of receipt of immunoglobulin products or expected receipt through 30 days after study vaccine dosing Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 30 days after final study vaccine 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 study vaccine dose Receipt of any inactivated (i.e., non-live) 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 HIV Living in the same home or enrolled in the same classroom at day care with infants <24 months of age (only one child per household may be enrolled into the study) Contact with pregnant caregiver A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 30 days after any study vaccine dose A household contact who is a health care provider in contact with immunocompromised patients 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 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

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>MEDI-534 at 10^4 TCID50 at 0, 2, and 4 months (Nasal spray) | Biological: MEDI-534<br>* Multiple doses of MEDI-534 or Placebo at 10^4 TCID50<br>|
| Active Comparator: 2<br>MEDI-534 at 10^5 TCID50 at 0, 2, and 4 months (Nasal Spray) | Biological: MEDI-534<br>* Multiple doses of MEDI-534 or Placebo at 10 ^5 TCID50.<br>|
| Active Comparator: 3<br>MEDI-534 at 10^6 TCID50 at 0, 2, and 4 months (Nasal Spray) | Biological: MEDI-534<br>* Multiple doses of MEDI-534 or Placebo at 10^6 TCID50.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Adverse Events (SEs) After Dose 1 | The SEs for this study included fever ≥ 100.4°F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, laryngitis, and epistaxis. | Days 0-28 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With SEs After Dose 2 | The SEs for this study included fever ≥ 100.4°F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, laryngitis, and epistaxis. | Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With SEs After Dose 3 | The SEs for this study included fever ≥ 100.4°F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, laryngitis, and epistaxis. | 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 Subjects With Medically-attended Lower Respiratory Illnesses (MA-LRIs) | An MA-LRI was a healthcare provider-confirmed diagnosis of 1 or more of the following: wheezing, pneumonia, croup, rhonchi (not cleared with cough or suctioning), rales, bronchitis, bronchiolitis, apnea. | Days 0 to 180 days after final dose or the end of the RSV season, whichever was later | 
| Number of Participants With Serious Adverse Events (SAEs) | Events resulting in death; were life-threatening; resulted in inpatient hospitalization/prolongation of hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly/birth defect in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and may have jeopardized the participant and required medical/surgical intervention to prevent one of the above outcomes. | Days 0-28 after any dose | 
| 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 the final dose or through the end of the RSV season, whichever was later | 

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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | Days 7, 12, and 28 after each dose and during visits for pre-specified illness symptoms occurring Day 0 through 28-34 days post each dose. | 
| Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 1 | Number of participants with nasal wash specimens that were positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 | Number of participants with nasal wash specimens that were positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | 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 positive for RSV or PIV3 by culture and identified as vaccine-type virus by RT-PCR. | Days 0-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Baseline | Pre-dose GMT of serum antibody response to RSV as measured by microneutralization assay. Limit of quantification is 5. For results reported as < 5, a value of 2.5 was imputed. | Baseline (Day 0 prior to Dose 1) | 
| Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 1 | Post dose GMT of serum antibody response to RSV as measured by microneutralization assay. Limit of quantification is 5. For results reported as < 5, a value of 2.5 was imputed. | Day 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 2 | Post dose GMT of serum antibody response to RSV as measured by microneutralization assay. Limit of quantification is 5. For results reported as < 5, a value of 2.5 was imputed. | Day 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 3 | Post dose GMT of serum antibody response to RSV as measured by microneutralization assay. Limit of quantification is 5. For results reported as < 5, a value of 2.5 was imputed. | Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies to PIV3 at Baseline | Post dose GMT of serum antibody response to PIV3 as measured by HAI assay. Limit of quantification is 4. For results reported as < 4, a value of 2 was imputed. | Baseline (Day 0 prior to Dose 1) | 
| Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 1 | Post dose GMT of serum antibody response to PIV3 as measured by HAI assay. Limit of quantification is 4. For results reported as < 4, a value of 2 was imputed. | Day 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 2 | Post dose GMT of serum antibody response to PIV3 as measured by HAI assay. Limit of quantification is 4. For results reported as < 4, a value of 2 was imputed. | Day 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 3 | Post dose GMT of serum antibody response to PIV3 as measured by HAI assay. Limit of quantification is 4. For results reported as < 4, a value of 2 was imputed. | Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Seroresponse to RSV 28 Days After Dose 1 | Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay. | Days 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With Seroresponse to RSV 28 Days After Dose 2 | Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay. | Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With Seroresponse to RSV 28 Days After Dose 3 | Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay. | Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 
| Number of Participants With Seroresponse to PIV3 28 Days After Dose 1 | Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay. | Days 28-34 after Dose 1 (Dose 1 was on Day 0) | 
| Number of Participants With Seroresponse to PIV3 28 Days After Dose 2 | Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay. | Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) | 
| Number of Participants With Seroresponse to PIV3 28 Days After Dose 3 | Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay. | Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lower Respiratory Tract Illness, RSV and PIV3 infection