Phase I, Randomized, Double-blinded, Placebo-Controlled Dose De-escalation Study to Evaluate Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) in Adults in a Flavivirus Endemic Area

NCT03008122 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16-0034HHSN272201300021I
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

This study is randomized, double-blinded, placebo-controlled, Phase 1, dose de-escalation study to evaluate the safety, reactogenicity, and immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) administered to healthy male and non-pregnant female adult subjects. This study will enroll 90 healthy male and non-pregnant female subjects between the ages of 21 and 49 and will be conducted at Ponce Medical School Foundation, Inc.-CAIMED in Ponce, Puerto Rico. The duration of each subject's participation is approximately 26 months from recruitment through the last study visit. The entire study is expected to take approximately 49 months to complete. Two dose levels will be evaluated. Each subject will receive either placebo or 5 mcg (Group 1) or 2.5 mcg (Group 2) of ZPIV administered by intramuscular (IM) injection on Days 1 and 29. Solicited local and systemic reactogenicity data will be collected from all subjects through Day 8 after each vaccination. All subjects will be monitored for occurrence of unsolicited adverse events until 28 days after the second vaccination. The study will consist of a screening period of up to 28 days, a vaccination period in which subjects will receive a prime dose of vaccine on Day 1 followed by a boost on Day 29, and a follow-up period of 24 months post boost vaccination. Primary objectives are: 1) Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at two different dose levels. 2) Compare the safety and reactogenicity of ZPIV after each vaccination, between dosage groups, and by pre-vaccination flavivirus immune status.

Conditions

Zika Virus Infection

Keywords

Flavivirus; Inactivated; Phase I; Vaccine; ZIKA; ZPIV

Outcome Measures

Primary Outcomes (73)

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for All Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for All Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 though Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Local Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Local Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The following injection site reactogenicity events were measured: pain, tenderness, pruritus, ecchymosis, erythema, and induration. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for All Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for All Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Solicited Systemic Events Post Dose 1 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 1 through Day 8

• Frequency and Severity of Solicited Systemic Events Post Dose 2 by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The following systemic solicited events were measured: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, diarrhea, abdominal pain, rash, and fever. Participants who reported not having a symptom are listed as "None", while participants who did not complete their Memory Aid or could not remember whether they had a symptom are listed as "Not Reported". Severity is the maximum severity reported over all solicited symptoms post dosing for each participant.

  Day 29 through Day 36

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for All Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive and DENV Seropositive Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seropositive and DENV Seronegative Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). Each participant was counted once per SOC. If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative and DENV Seropositive Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Severity of Unsolicited Adverse Events by Treatment Group for Baseline ZIKV Seronegative and DENV Seronegative Participants

  Adverse events (AEs) are defined as any untoward medical occurrence regardless of its causal relationship to study treatment. Number of participants with an AE are summarized by MedDRA System Organ Class (SOC). If a condition was present at screening, it was not considered an AE unless the severity worsened.

  Day 1 through Day 57

• Frequency and Type of Serious Adverse Events (SAE) Considered Related to Study Vaccine for All Participants

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

  Day 1 through Day 750

• Duration of Serious Adverse Events (SAE) Considered Related to Study Vaccine for All Participants

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

  Day 1 through Day 750

• Frequency and Type of Adverse Events of Special Interest (AESI) Considered Related to Study Vaccine for All Participants

  For this study Neurologic and Neuroinflammatory Disorders after the first vaccination were considered as Adverse Events of Special Interest (AESI).

  Day 1 through Day 750

• Duration of Adverse Events of Special Interest (AESI) Considered Related to Study Vaccine for All Participants

  For this study Neurologic and Neuroinflammatory Disorders after the first vaccination were considered as Adverse Events of Special Interest (AESI).

  Day 1 through Day 750

• Frequency of New Onset Chronic Medical Conditions for All Participants

  New onset chronic medical conditions (NOCMCs) were any new medical conditions reported from the first administration of study vaccine until the end of the study.

  Day 1 through Day 750

• Comparison of Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for All Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for All Participants

  The number of participants experiencing each adverse event are listed.

  Day 29 through Day 36

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive Participants

  The number of participants experiencing each adverse event are listed.

  Day 29 through Day 36

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative Participants

  The number of participants experiencing each adverse event are listed.

  Day 29 through Day 36

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The number of participants experiencing each adverse event are listed.

  Day 29 through Day 36

• Comparison of the Frequency, Type, and Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The number of participants experiencing each adverse event and the median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Frequency, Type, and Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seronegative Participants

  The number of participants experiencing each adverse event and the median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The number of participants experiencing each adverse event will be listed

  Day 29 through Day 36

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The number of participants experiencing each adverse event are listed.

  Day 1 through Day 8

• Comparison of the Frequency and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The number of participants experiencing each adverse event are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for All Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for All Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seropositive and DENV Seropositive Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type Duration of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seropositive Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 1 for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The median duration of adverse events are listed.

  Day 1 through Day 8

• Comparison of the Duration and Type of Vaccine-related Grade 3 Local, Systemic, or Laboratory AE, and Grade 2 or Greater Local or Systemic Reactogenicity Post Dose 2 for Baseline ZIKV Seronegative and DENV Seronegative Participants

  The median duration of adverse events are listed.

  Day 29 through Day 36

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for All Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive and DENV Seropositive Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seropositive and DENV Seronegative Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative and DENV Seropositive Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

• Comparison of Study Withdrawals and Discontinuation of Study Vaccination Due to Any Reason for Baseline ZIKV Seronegative and DENV Seronegative Participants

  Comparisons of the number of participants who withdrew early and who discontinued treatment are presented.

  Day 1 through Day 750

Study Arms (2)

Group 1

EXPERIMENTAL

5 mcg ZPIV administered IM in a homologous prime-boost regimen on Day 1 and Day 29 , n=45 (2 sentinels, 43 non-sentinels) or placebo, n=5

Other: Placebo; Biological: Zika Virus Purified Inactivated Vaccine (ZPIV)

Group 2

EXPERIMENTAL

2.5 mcg ZPIV administered IM in a homologous prime-boost regimen on Day 1 and Day 29, n=35 or placebo, n=5

Other: Placebo; Biological: Zika Virus Purified Inactivated Vaccine (ZPIV)

Interventions

Placebo OTHER

Placebo

Group 1; Group 2

Zika Virus Purified Inactivated Vaccine (ZPIV) BIOLOGICAL

Zika Virus Purified Inactivated Vaccine with aluminum hydroxide adjuvant.

Group 1; Group 2

Eligibility Criteria

• Age: 21 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be a male or non-pregnant, non-breastfeeding female between the age of 21 and 49 years, inclusive at the time of screening and enrollment.
• Must be willing and able to read, sign and date the informed consent document before study related procedures are performed.
• Must be willing and able to comply with study requirements and available for follow-up visits for the entire study.
• Must have a means to be contacted by telephone.
• Must have a body mass index (BMI) \> /= 18.1 and \< 35.0 kg/m2.
• Must have acceptable\* screening laboratory findings within 28 days before enrollment.
• Acceptable clinical laboratory parameters include:
• Hemoglobin: women: \> /= 11.5 g/dL; men \> /= 13.5 g/dL
• Hemotocrit: women: \> /= 34.5%; men \> /= 40.5%
• White blood cell count: \> /= 3.500 cells/mm3 but \< /= 10,800 cells/mm3
• Platelets: \> /= 150,000 but \< /= 450,000 per mm3
• Urine dipstick (clean urine sample): protein \< 1+, glucose negative
• Serum creatinine \< /= 1 x institutional upper limit of normal (ULN)
• Blood urea nitrogen (BUN) \< 25
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 1.25 x institutional ULN

You may not qualify if:

• Note 2: An abbreviated physical exam differs from a complete exam in that it does not include a genitourinary and rectal exam.
• Note 3: Vital signs must be normal by protocol toxicity grading scale or determined to be normal-variant by investigator. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate may be re-measured. Repeated vital signs may be used to determine eligibility.
• Women of childbearing potential\* must have a negative serum pregnancy test at screening and a negative urine pregnancy test immediately prior to each vaccination.
• Note: All female subjects are considered of childbearing potential unless postmenopausal or surgically sterilized and \> /= 3 months have passed since sterilization procedure. Postmenopausal is defined as amenorrhea for \> /= 12 months without an alternative medical cause. Permanent female sterilization procedures include tubal ligation, bilateral salpingectomy, hysterectomy, bilateral oophorectomy, or successful Essure placement.
• Women of childbearing potential must use an acceptable method of contraception\* from one month (30 days) prior to the first vaccination until the end of the study.
• \*Acceptable methods of contraception include the following:
• Use highly effective contraceptive methods, defined by \< 1% failure rate per year independent of user adherence, including long-acting reversible contraception (LARC): progestin-releasing subdermal implants and intrauterine devices (IUD), OR
• Use effective contraceptive methods, defined by 5-9% failure rate with typical use and \< 1% failure rate with consistent and correct use, including: prescription oral contraceptives, contraceptive injections, combined pill, progestin-only pill, hormone-releasing transdermal patch or vaginal ring, and depot medroxyprogesterone acetate injection (Depo-Provera), OR
• Male sex partners must have had a vasectomy \> /= 3 months prior to first vaccination, OR
• Practice abstinence defined as refraining from heterosexual intercourse from 30 days before first vaccination until the end of the study.
• Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening period until the end of the study.
• Subjects must provide concurrent consent at the time of enrollment and 1st vaccination to future use of stored blood samples to measure immunity to ZIKV.
• Has plans to become pregnant during the course of the study, or is currently pregnant or breastfeeding.
• Plans to receive a licensed flavivirus vaccine or participate in another flavivirus vaccine trial during the study.
• Has positive serology for HIV 1/2, Hepatitis C virus, or Hepatitis B surface antigen.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Ponce School of Medicine CAIMED Center

Ponce, 00716, Puerto Rico

Location

MeSH Terms

Conditions

Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Results Point of Contact

• Title: Sarah George, MD
• Organization: Saint Louis University

sarah.george@health.slu.edu

314-977-9035

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: January 2, 2017
• Study Start: March 21, 2017
• Primary Completion: August 10, 2021
• Study Completion: August 10, 2021
• Last Updated: April 6, 2023
• Results First Posted: April 6, 2023

Record last verified: 2018-01

Locations

PR (1)