Safety and Tolerability Study to Evaluate MEDI-534 in Children 6 to < 24 Months of Age (CP149)

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections; Respiratory Viral Infections; Parainfluenza Virus 3, Human
• Intervention / Treatment: Biological: MEDI-534; Biological: MEDI-534; Biological: MEDI-534

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Conway, Arkansas, United States, 72033
      • Arkansas Pediatric Research Division
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Pediatric Clinic
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Palm Beach Gardens, Florida, United States, 33410
      • Pediatric Partners
  • Georgia
    • Dalton, Georgia, United States, 30721
      • North Georgia Clinical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy and Immunology
    • Chicago, Illinois, United States, 61614
      • Children's Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts-New England Medical Center
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Craig A. Spiegel, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
  • New York
    • Binghamton, New York, United States, 13901
      • United Medical Associates
    • Mineola, New York, United States, 11501
      • Withrop University Hospital
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center Mercy Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • Primary Physicians Research, Inc.
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Sanford Children's Specialty Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center of Houston Medical School
  • Utah
    • Ogden, Utah, United States, 84405
      • Bear Care Pediatrics
    • South Jordan, Utah, United States, 84095
      • CopperView Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
    • Vienna, Virginia, United States, 22180
      • Advanced Pediatrics
  • Washington
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic Research Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall University Joan C. Edwards School of Medicine
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 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)

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Bernstein DI, Malkin E, Abughali N, Falloon J, Yi T, Dubovsky F; MI-CP149 Investigators. Phase 1 study of the safety and immunogenicity of a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine in seronegative children. Pediatr Infect Dis J. 2012 Feb;31(2):109-14. doi: 10.1097/INF.0b013e31823386f1.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: June 26, 2007
• First Submitted That Met QC Criteria: June 27, 2007
• First Posted (Estimate): June 28, 2007

Study Record Updates

• Last Update Posted (Estimate): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 13, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Lower Respiratory Tract Illness; RSV and PIV3 infection
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Disease Attributes; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Virus Diseases; Respiratory Syncytial Virus Infections; Paramyxoviridae Infections
• Other Study ID Numbers: MI-CP149