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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: MedImmune LLC

Current Primary Outcome:

  • 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) ]
  • Number of Participants With SEs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ]
  • 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) ]
  • Number of Participants With Adverse Events (AEs) After Dose 1 [ Time Frame: Days 0-28 after Dose 1 (Dose 1 was on Day 0) ]
    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) ]
    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) ]
    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) ]
  • Number of Participants With MA-LRIs After Dose 2 [ Time Frame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64) ]
  • Number of Participants With MA-LRIs

    Original Primary Outcome:

    • Incidence of solicited and unsolicited adverse events from administration of study vaccine through 28 days following each dose [ Time Frame: Day 0 through 28 days after each dose ]
    • Incidence of medically attended lower respiratory infections and serious adverse events from administration of study vaccine following each dose [ Time Frame: Day 0 through 28 days after each dose ]
    • Description of significant medical conditions from administration of study vaccine through day 180 post-final dose [ Time Frame: Day 0 through 180 - post-final dose ]


    Current Secondary Outcome:

    • 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. ]
      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) ]
      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) ]
      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) ]
      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) ]
    • 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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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) ]
      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 considere

      Original Secondary Outcome:

      • Incidence of viral shedding of MEDI-560 [ Time Frame: Days 7, 12, and 28 after each dose ]
      • Percentage of vaccinated subjects with HAI seroconversion, defined as great than or equal to a 4-fold rise in HAI titer from baseline, and geometric mean titers (GMT) pre and post dosing. [ Time Frame: Days 7, 12, and 28 after each dose ]
      • Description of the genotypic and phenotypic stability on recovered vaccine virus [ Time Frame: Days 7, 12, and 28 after each dose ]


      Information By: MedImmune LLC

      Dates:
      Date Received: July 27, 2007
      Date Started: October 2007
      Date Completion:
      Last Updated: November 28, 2011
      Last Verified: November 2011