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

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00493285
First received: June 26, 2007
Last updated: July 13, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Respiratory Viral Infections
Respiratory Syncytial Virus Infections
Parainfluenza Virus 3, Human
Biological: MEDI-534
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Number of Participants With Solicited Adverse Events (SEs) After Dose 1 [ Time Frame: Days 0-28 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With SEs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With SEs After Dose 3 [ Time Frame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Adverse Events (AEs) After Dose 1 [ Time Frame: Days 0-28 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: Yes ]
    Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 1.

  • Number of Participants With AEs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: Yes ]
    Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 2.

  • Number of Participants With AEs After Dose 3 [ Time Frame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: Yes ]
    Unsolicited AEs reported by 1 or more participants in either treatment group through 28 days post Dose 3.

  • Number of Subjects With Medically-attended Lower Respiratory Illnesses (MA-LRIs) [ Time Frame: Days 0 to 180 days after final dose or the end of the RSV season, whichever was later ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Days 0-28 after any dose ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Significant New Medical Conditions (SNMCs) [ Time Frame: Day 0 through 180 days after the final dose or through the end of the RSV season, whichever was later ] [ Designated as safety issue: Yes ]
    A SNMC is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant.


Secondary Outcome Measures:
  • Number of Participants Shedding Vaccine-like Virus at Any Time During Study Participation [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 1 [ Time Frame: Days 7-10 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 1 [ Time Frame: Days 12-18 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 1 [ Time Frame: Days 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 1 [ Time Frame: Days 0-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 2 [ Time Frame: Days 7-10 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 2 [ Time Frame: Days 12-18 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 2 [ Time Frame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 2 [ Time Frame: Days 0-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 3 [ Time Frame: Days 7-10 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 3 [ Time Frame: Days 12-18 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 3 [ Time Frame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 3 [ Time Frame: Days 0-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Baseline [ Time Frame: Baseline (Day 0 prior to Dose 1) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 1 [ Time Frame: Day 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 2 [ Time Frame: Day 28-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 3 [ Time Frame: Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies to PIV3 at Baseline [ Time Frame: Baseline (Day 0 prior to Dose 1) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 1 [ Time Frame: Day 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 2 [ Time Frame: Day 28-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 3 [ Time Frame: Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Seroresponse to RSV 28 Days After Dose 1 [ Time Frame: Days 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay.

  • Number of Participants With Seroresponse to RSV 28 Days After Dose 2 [ Time Frame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay.

  • Number of Participants With Seroresponse to RSV 28 Days After Dose 3 [ Time Frame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in RSV antibody from baseline as measured by microneutralization assay.

  • Number of Participants With Seroresponse to PIV3 28 Days After Dose 1 [ Time Frame: Days 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay.

  • Number of Participants With Seroresponse to PIV3 28 Days After Dose 2 [ Time Frame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay.

  • Number of Participants With Seroresponse to PIV3 28 Days After Dose 3 [ Time Frame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2) ] [ Designated as safety issue: No ]
    Seroresponse is equal to or greater than a 4-fold rise in PIV3 antibody from baseline as measured by HAI assay.


Enrollment: 49
Study Start Date: July 2007
Study Completion Date: April 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 ^5 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 10^6 TCID50.

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.

  Eligibility

Ages Eligible for Study:   6 Months to 23 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00493285

  Show 30 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Elissa Malkin, D.O. MedImmune LLC
  More Information

Additional Information:
Publications:
Responsible Party: Elissa Malkin, D.O., MedImmune LLC
ClinicalTrials.gov Identifier: NCT00493285     History of Changes
Other Study ID Numbers: MI-CP149
Study First Received: June 26, 2007
Results First Received: March 12, 2012
Last Updated: July 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Lower Respiratory Tract Illness
RSV and PIV3 infection

Additional relevant MeSH terms:
Paramyxoviridae Infections
Respiratory Syncytial Virus Infections
Virus Diseases
Mononegavirales Infections
RNA Virus Infections
Pneumovirus Infections

ClinicalTrials.gov processed this record on April 16, 2014