A Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to <24 Month-old Children and in 2 Month-old Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00686075
First received: May 23, 2008
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

Primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 in children 6 to less than (<) 24 months of age and in infants 2 months of age.


Condition Intervention Phase
Healthy
Biological: MEDI-534, Cohort 1
Other: Placebo, Cohort 1
Biological: MEDI-534, Cohort 2
Other: Placebo, Cohort 2
Biological: MEDI-534, Cohort 3
Other: Placebo, Cohort 3
Biological: MEDI-534, Cohort 4
Other: Placebo, Cohort 4
Biological: MEDI-534, Cohort 5
Other: Placebo, Cohort 5
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, a Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to < 24 Month-old Children and in 2 Month-old Infants

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Number of Participants With Solicited Symptoms After Dose 1 [ Time Frame: Within 28 days after Dose 1 ] [ Designated as safety issue: Yes ]
    Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever greater than or equal to (>=) 100.4 degrees Fahrenheit (F), runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.

  • Number of Participants With Solicited Symptoms After Dose 2 [ Time Frame: Within 28 days after Dose 2 ] [ Designated as safety issue: Yes ]
    Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever >=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.

  • Number of Participants With Solicited Symptoms After Dose 3 [ Time Frame: Within 28 days after Dose 3 ] [ Designated as safety issue: Yes ]
    Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever >=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 1 [ Time Frame: Within 28 days after Dose 1 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAEs) for Dose 1 are events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 1 were reported.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 2 [ Time Frame: Within 28 days after Dose 2 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 2 are events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 2 were reported.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 3 [ Time Frame: Within 28 days after Dose 3 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 3 are events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 3 were reported.

  • Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 1 [ Time Frame: Within 28 days after Dose 1 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 1 were reported.

  • Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 2 [ Time Frame: Within 28 days after Dose 2 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 2 were reported.

  • Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 3 [ Time Frame: Within 28 days after Dose 3 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 3 were reported.

  • Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1 [ Time Frame: Within 28 days after Dose 1 ] [ Designated as safety issue: Yes ]
    An MA-LRI was a healthcare provider-confirmed diagnosis of one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, and apnea.

  • Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 2 [ Time Frame: Within 28 days after Dose 2 ] [ Designated as safety issue: Yes ]
    An MA-LRI was a healthcare provider-confirmed diagnosis of one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, and apnea.

  • Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 3 [ Time Frame: Within 28 days after Dose 3 ] [ Designated as safety issue: Yes ]
    An MA-LRI was a healthcare provider-confirmed diagnosis of one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, and apnea.


Secondary Outcome Measures:
  • Number of Participants Who Shed Vaccine-Type Virus [ Time Frame: 7, 12 and 28 days after Dose 1, 2 and 3 ] [ Designated as safety issue: No ]
    Nasal wash specimens were collected to assess vaccine virus recovery in the upper respiratory tract on 7, 12 and 28 days after each dosing.

  • Percentage of Participants With a Seroresponse to Respiratory Syncytial Virus (RSV) and Human Parainfluenza Virus Type 3 (hPIV3) After Dose 3 [ Time Frame: Day 28 after Dose 3 ] [ Designated as safety issue: No ]
    Seroresponse was defined as a >=4-fold rise from Baseline in neutralizing antibody titer, regardless of Baseline serostatus. Respiratory Syncytial Virus (RSV) and hPIV3 antibody titers were determined by using microneutralization assay and hemagglutination inhibition assay, respectively. Clopper-pearson exact confidence interval was reported.

  • Genotypic Stability of Recovered Vaccine-Type Virus [ Time Frame: Within 28 days after any dose ] [ Designated as safety issue: No ]
    Nasal wash samples with vaccine-type virus were evaluated for genotypic stability, defined as the presence of the entire RSV-Fusion (RSV F) insert based on the RSV F sequence results. If the insert was absent or truncated, the recovered virus was counted as genotypically unstable. Nasal wash samples were categorized as genotypically stable, genotypically unstable or undetermined genotypic stability.

  • Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) Through 365 Days After Randomization [ Time Frame: Day 0 to Day 365 ] [ Designated as safety issue: Yes ]
    An MA-LRI was a healthcare provider-confirmed diagnosis of one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, and apnea. MA-LRIs occurring within 28 days post any dose and after 28 days post any dose were summarized separately.

  • Number of Participants With Significant New Medical Conditions (SNMCs) Through 365 Days After Randomization [ Time Frame: Day 0 to Day 365 ] [ Designated as safety issue: Yes ]
    An SNMC was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of SNMCs include diabetes, asthma, autoimmune disease (for example, lupus, rheumatoid arthritis), and neurological disease (for example, epilepsy, autism).

  • Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through 365 Days After Randomization [ Time Frame: Day 0 to Day 365 ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events after administration of drug which were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) within 365 days after randomization were reported.


Enrollment: 1338
Study Start Date: June 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI-534, Cohort 1
Participants aged 6 to less than (<) 24 months will receive MEDI-534, 10^5 median tissue culture infectious dose (TCID50) by intranasal route at Month 0, 2, and 4.
Biological: MEDI-534, Cohort 1
Participants aged 6 to less than (<) 24 months will receive MEDI-534, 10^5 median tissue culture infectious dose (TCID50) by intranasal route at Month 0, 2, and 4.
Placebo Comparator: Placebo, Cohort 1
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Other: Placebo, Cohort 1
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Experimental: MEDI-534, Cohort 2
Participants aged 6 to <24 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Biological: MEDI-534, Cohort 2
Participants aged 6 to <24 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo Comparator: Placebo, Cohort 2
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Other: Placebo, Cohort 2
Participants aged 6 to <24 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Experimental: MEDI-534, Cohort 3
Participants aged 2 months will receive MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.
Biological: MEDI-534, Cohort 3
Participants aged 2 months will receive MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo Comparator: Placebo, Cohort 3
Participants aged 2 months will receive placebo matched to MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.
Other: Placebo, Cohort 3
Participants aged 2 months will receive placebo matched to MEDI-534, 10^4 TCID50 by intranasal route at Month 0, 2, and 4.
Experimental: MEDI-534, Cohort 4
Participants aged 2 months will receive MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Biological: MEDI-534, Cohort 4
Participants aged 2 months will receive MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo Comparator: Placebo, Cohort 4
Participants aged 2 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Other: Placebo, Cohort 4
Participants aged 2 months will receive placebo matched to MEDI-534, 10^5 TCID50 by intranasal route at Month 0, 2, and 4.
Experimental: MEDI-534, Cohort 5
Participants aged 2 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Biological: MEDI-534, Cohort 5
Participants aged 2 months will receive MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo Comparator: Placebo, Cohort 5
Participants aged 2 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.
Other: Placebo, Cohort 5
Participants aged 2 months will receive placebo matched to MEDI-534, 10^6 TCID50 by intranasal route at Month 0, 2, and 4.

Detailed Description:

This is a Phase 1/2a, randomized, double-blind, placebo-controlled, dose-escalation, multicenter study to evaluate the safety and tolerability of multiple doses of MEDI-534 at 10^5 or 10^6 median tissue culture infectious dose (TCID50) in RSV and PIV3 seronegative children 6 to <24 months of age and at dosages of 10^4, 10^5 or 10^6 TCID50 in unscreened infants 2 months of age.

  Eligibility

Ages Eligible for Study:   2 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 falls within one of the two age groups:

    6 to less than (<) 24 months (more than [>] 6 months of age and not yet reached their 2nd year birthday), Cohorts 1 and 2 2 months (+/- 4 weeks), Cohorts 3, 4, and 5

  • Cohorts 1 and 2 only: Subject is seronegative to both Respiratory Syncytial Virus (RSV) and human Parainfluenza Virus Type 3 (hPIV3) at Screening
  • Subject whose gestational age was greater than or equal to (>=) 36 weeks
  • Subject is in general good health with normal growth (that is, body weight greater than (>) third percentile per world health organization [WHO] simplified weight-per-age field tables
  • Subject's legal representative is available by telephone
  • Written informed consent and Health Insurance Portability and Accountability Act (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 1-year after receipt of the first dose of study vaccine
  • 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 (>=100.4 degrees Fahrenheit [>=38.0 degrees Celsius], 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 interfere with intranasal delivery of study vaccine
  • Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time 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 study vaccine dosing, except that infrequent use of over-the-counter medications for the systemic treatment of common childhood symptoms (that is, pain relievers, decongestants or cough suppressants) are permitted according to the judgment of the investigator
  • Any current or expected receipt of immunosuppressive agents including steroids (>=2 milligram per kilogram [mg/kg] per day of prednisone or its equivalent, or >=20 milligram per day [mg/day] if the subject weighs >10 kilogram [kg], given daily or on alternate days for >=14 days); children in this category should not receive study vaccine 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 the protocol-specified blood collection at 28 days after final study dosing
  • History of receipt of immunoglobulin products or expected receipt through the protocol-specified blood collection at 28 days after final study dosing
  • Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 180 days after final study dosing
  • Receipt of any live virus vaccine (excluding oral polio vaccine and 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 (that is, non-live) vaccine or oral polio 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 human immunodeficiency virus (HIV) infection
  • Expected to be living in the same home or enrolled in the same classroom at day care with infants <6 months within 28 days after each dose
  • Living in a household with another child who is concurrently enrolled in a study of a live viral vaccine (including this study)
  • Expected contact with a pregnant caregiver within 28 days after each dose
  • A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after any study vaccine dose
  • Expected household contact within 28 days after each dose with a health care provider for immunocompromised subjects 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 for respiratory illness (excludes elective mechanical ventilation during surgery for subjects in Cohorts 1 and 2)
  • 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: NCT00686075

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

Additional Information:
No publications provided by MedImmune LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00686075     History of Changes
Other Study ID Numbers: MI-CP178
Study First Received: May 23, 2008
Results First Received: September 22, 2014
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Respiratory Syncytial Virus (RSV)
Parainfluenza Virus Type 3 (PIV3)
MEDI-534

ClinicalTrials.gov processed this record on October 21, 2014