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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493285

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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:
Infection
Communicable Diseases
Virus Diseases
Respiratory Syncytial Virus Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on September 18, 2014