A Phase 1/2A Study to Evaluate the Safety, Immunogenicity, and Shedding of MEDI-560 in Infants 1 to < 12 Months of Age

This study has been terminated.
(The study was closed prior to enrollment of Cohort 2 due to a non-safety related sponsor decision.)
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00508651
First received: July 27, 2007
Last updated: November 28, 2011
Last verified: November 2011
  Purpose

The primary objective of this study is to describe the safety and tolerability of 3 doses of MEDI-560 at 10^5 TCID50 when administered to children 6 to < 12 months of age who are HPIV3 (human parainfluenza virus type 3) seronegative at baseline and to infants 1 to < 3 months of age regardless of baseline serostatus.


Condition Intervention Phase
Healthy
Biological: MEDI-560
Biological: Placebo
Phase 1
Phase 2

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: An Expanded Phase1/2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Viral Shedding of MEDI-560, A Live, Attenuated Recombinant Parainfluenza Virus Type 3 (PIV3) Vaccine, Administered Intranasally to Healthy Infants 1 to <12 Mos. 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 ]
  • 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 ]
  • 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 ]
  • 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 Participants With Medically Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1 [ Time Frame: Days 0-28 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: Yes ]
  • Number of Participants With MA-LRIs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: Yes ]
  • Number of Participants With MA-LRIs 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 ]
  • Number of Participants With Serious Adverse Events (SAEs) After Dose 1 [ Time Frame: Days 0-28 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: Yes ]
  • Number of Participants With SAEs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ] [ Designated as safety issue: Yes ]
    One participant had event of pneumonia after Dose 2.

  • Number of Participants With SAEs 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 ]
  • Number of Participants With Significant New Medical Conditions (SNMCs) [ Time Frame: Day 0 through 180 days after final dose ] [ 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 180 days post final dose. ] [ Designated as safety issue: No ]
    Number of participants with nasal wash specimens that were culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • 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 culture positive for HPIV3 in which vaccine-like virus was identified.

  • Number of Participants With Hemagglutination Inhibition (HAI) Seroconversion/Seroresponse to HPIV3 28 Days After Dose 1 [ Time Frame: Days 28-34 after Dose 1 (Dose 1 was on Day 0) ] [ Designated as safety issue: No ]
    Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid.

  • Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 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 ]
    Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid.

  • Number of Participants With HAI Seroconversion/Seroresponse to HPIV3 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 ]
    Hemagglutination inhibition seroconversion/seroresponse is equal to or greater than a 4-fold rise in HAI antibody titer from baseline. Hemagglutination inhibition antibody results obtained on or after detection of wild-type HPIV3 in culture were not considered valid.

  • Number of Nasal Wash Samples Containing Vaccine-like Virus in the Absence of Admixture With Wild-type HPIV3 in Which the Vaccine-like Virus Was Genotypically Stable [ Time Frame: Day 0 after Dose 1 to 180 days after the final dose ] [ Designated as safety issue: No ]
    A nasal wash specimen was collected at screening and on Days 7 (7-10), 12 (12-18), and 28 (28-34) post each dose and during visits for pre-specified illness symptoms occurring Day 0 through 180 days post final dose to assess vaccine virus replication. Genotypic stability of recovered vaccine-type virus at the 15 mutations of phenotypic importance was assessed.

  • Number of Nasal Wash Samples Containing Vaccine-like Virus in the Absence of Admixture With Wild-type HPIV3 in Which the Vaccine-like Virus Was Phenotypically Stable [ Time Frame: Day 0 after Dose 1 to 180 days after the final dose ] [ Designated as safety issue: No ]
    A nasal wash specimen was collected at screening and on Days 7 (7-10), 12 (12-18), and 28 (28-34) post each dose and during visits for pre-specified illness symptoms occurring Day 0 through 180 days post final dose to assess vaccine virus replication. Determination of the temperature sensitivity of recovered vaccine-type virus.

  • Geometric Mean Titers (GMTs) of Serum HAI Antibodies to HPIV3 at Baseline [ Time Frame: Baseline (Day 0 prior to Dose 1) ] [ Designated as safety issue: No ]
    Pre-dose GMT of HAI antibody to HPIV3

  • Geometric Mean Titers of Serum Antibodies to HPIV3 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 1 GMT of HAI antibody to HPIV3

  • Geometric Mean Titers of Serum Antibodies to HPIV3 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 2 GMT of HAI antibody to HPIV3

  • Geometric Mean Titers of Serum Antibodies to HPIV3 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 3 GMT of HAI antibody to HPIV3


Enrollment: 30
Study Start Date: October 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 MEDI-560
MEDI-560 vaccine was a frozen preparation of live, attenuated rHPIV3cp45 virus filled into Becton Dickinson^TM Luer slip tip syringes. Each 0.2 mL dose contained 10^5 TCID50 of MEDI-560 in a sucrose phosphate glutamate buffer.
Biological: MEDI-560
MEDI-560 vaccine was a frozen preparation of live, attenuated rHPIV3cp45 virus filled into Becton Dickinson^TM luer slip tip syringes. Each 0.2 mL dose contained 10^5 TCID50 of MEDI-560 in a sucrose phosphate glutamate buffer.
Placebo Comparator: Cohort 1 Placebo
Placebo was a frozen preparation filled into Becton Dickinson^TM Luer slip-tip syringes. Each 0.2 mL dose contained sucrose phosphate buffer.
Biological: Placebo
Placebo was a frozen preparation filled into Becton Dickinson^TM luer slip-tip syringes. Each 0.2 mL dose contained sucrose phosphate buffer.

Detailed Description:

This is a randomized, double-blind, placebo-controlled, multidose Phase 1/2a multicenter study designed to evaluate the safety, tolerability, viral shedding, immunogenicity, and genotypic and phenotypic stability of MEDI-560 in infants 1 to < 12 months of age. Three doses of MEDI-560 at a dosage level of 10^5 TCID50 were administered 0, 2, and 4 months after enrollment to a 30-participant cohort of 6 to < 12 month-old HPIV3 seronegative children randomized 2:1 to MEDI-560 vs placebo. A second 160-participant cohort of 1 to < 3 month-old infants not screened for baseline serostatus was planned but was not opened to enrollment for reasons other than safety. Participants were followed for safety through 180 days post last dose. Nasal wash specimens were collected at screening and Days 7, 12, and 28 following each dose and during unscheduled illness visits to assess vaccine virus shedding and genotypic and phenotypic stability of any shed vaccine virus. Blood was collected at screening to determine eligibility and prior to Dose 1 for baseline serostatus. Blood for assessment of antibodies to HPIV3 was collected approximately 7 to 12 days after Dose 1 and Dose 3 and 1 month after each dose for antibodies to PIV3.

  Eligibility

Ages Eligible for Study:   1 Month to 11 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female whose age on the day of randomization falls within one of the two age cohorts:

    Cohort 1: 6 to < 12 months (≥ 6 months of age and not yet reached their 1st year birthday); Cohort 2: 1 to < 3 months (> 28 days of age and not yet reached their 3rd month birthday)

  2. Cohort 1 only: Participant is seronegative to HPIV3 at screening as determined by ELISA; or the legal representative is willing to provide access to data documenting that the participant was screened for another MedImmune trial after written informed consent was obtained, and that the participant is seronegative to HPIV3 within 21 days prior to randomization into MI-CP150 as determined by ELISA at MedImmune
  3. Participant was the product of a normal full term pregnancy, defined as 36-42 weeks gestation
  4. Participant is in general good health
  5. Participant's legal representative is available by telephone
  6. Written informed consent and Health Insurance Portability and Accountability Act authorization (if applicable) obtained from the participant's legal representative
  7. Participant's legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator
  8. Participant is available to complete the follow-up period of 180 days after the final dose of investigational product as required by the protocol
  9. Participant's legal representative is willing and able to bring the subject to the study site for evaluation of respiratory illness in accordance with the protocol

Exclusion Criteria:

  1. Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization
  2. Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of investigational product
  3. Cohort 1 only: weight < the fifth percentile for age on the day of randomization
  4. Cohort 2 only: history of low birth-weight (ie, < 2,500 grams at birth) or weight < fifth percentile for age on the day of randomization
  5. 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 investigational product dosing, except that infrequent use of over-the-counter medications such as pain relievers are permitted according to the judgment of the investigator
  6. Any current or expected receipt of immunosuppressive agents including steroids (≥ 2 mg/kg per day of prednisone or its equivalent, or ≥ 20 mg/day if the participant weighs >10 kg, given daily or on alternate days for ≥ 14 days); children in this category should not receive investigational product 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
  7. History of receipt of blood transfusion or expected receipt through 30 days after final investigational product dosing
  8. History of receipt of immunoglobulin products or expected receipt through 30 days after final investigational product dosing
  9. Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 30 days after final investigational product dosing
  10. 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 dose
  11. Receipt of any inactivated (eg, non-live) vaccine or rotavirus vaccine within 14 days prior to randomization or expected receipt within a 14-day window around any dose
  12. Known or suspected immunodeficiency, including human immunodeficiency virus
  13. Living in the same home or enrolled in the same classroom at day care with infants < 24 months of age within 28 days after each dose (only one child per household may be enrolled into the study)
  14. Contact with pregnant caregiver within 28 days after each dose
  15. Household contact with an immunocompromised person within 28 days after each dose; the participant should also avoid close contact with immunocompromised individuals for at least 28 days after each investigational product dose
  16. Household contact within 28 days after each dose with a healthcare worker who has direct patient care responsibilities or household contact within 28 days after each dose with someone who is a day care provider or preschool teacher for children < 24 months of age
  17. History of allergic reaction to any component of the investigational product
  18. Previous medical history or evidence of an intercurrent or chronic illness that, in the opinion of the investigator, may compromise the safety of the participant
  19. Known or suspected active or chronic hepatitis infection
  20. History of medical diagnosis of asthma, reactive airway disease, wheezing requiring medication, bronchoconstriction or treatment with a β2 agonist (eg, albuterol), cystic fibrosis, chronic lung disease of prematurity (eg, bronchopulmonary dysplasia), chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation
  21. A family member or a household contact who is an employee of the research center or otherwise involved with the conduct of the study
  22. Any condition that, in the opinion of the investigator, might interfere with investigational product 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: NCT00508651

  Show 23 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Judith Falloon, MD MedImmune LLC
  More Information

Additional Information:
Publications:
Responsible Party: Judith Falloon , MD, MedImmune, LLC
ClinicalTrials.gov Identifier: NCT00508651     History of Changes
Obsolete Identifiers: NCT01150799
Other Study ID Numbers: MI-CP150
Study First Received: July 27, 2007
Results First Received: September 8, 2011
Last Updated: November 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
parainfluenza virus, children, vaccine

ClinicalTrials.gov processed this record on October 19, 2014