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PIZV

Phase 1

Virus, Zika | Monoclonal antibody | Infectious Disease |Takeda Pharmaceutical Company Limited|Last Updated: Feb 11, 2022

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment271
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03343626Safety, Immunogenicity, and Dose Ranging Study of Inactivated Zika Virus Vaccine in Healthy ParticipantsPHASE1 COMPLETED 271Nov 13, 2017Nov 24, 2020Feb 11, 20229 United States, Puerto Rico
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Study Endpoints
Primary Endpoints
Percentage of Participants With Solicited Local Injection Site Reactions by Severity Within 7 Days After Dose 1 of PIZV or Placebo
Within 7 days after Dose 1 (Day 8)

Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after first vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), erythema (\<25 mm, mild: \>=25 to- \<=50 mm, moderate: \>50 to \<=100 mm, severe: \>100 mm), and swelling and induration (\<25 mm, mild: \>=25 to \<=-50 mm, moderate: \>50 to \<=100 mm, severe: \>100 mm). Only categories for which there was at least 1 participant are reported.

Percentage of Participants With Solicited Local Injection Site Reactions by Severity Within 7 Days After Dose 2 of PIZV or Placebo
Within 7 days after Dose 2 (Day 36)

Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after first vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), erythema (\<25 mm, mild: \>=25 to \<=50 mm, moderate: \>50 to \<=100 mm, severe: \>100 mm), and swelling and induration (\<25 mm, mild: \>=25 to \<=50 mm, moderate: \>50 to \<=100 mm, severe: \>100 mm). Only categories for which there was at least 1 participant are reported.

Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity Within 7 Days After Dose 1 of PIZV or Placebo
Within 7 days after Dose 1 (Day 8)

Solicited systemic AEs included fever, headache, fatigue, malaise, arthralgia, and myalgia that occurred within 7 days of first vaccination. Solicited systemic AEs (headache, fatigue, malaise, arthralgia, and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was graded from 1 to 4 by severity; where 1=Mild: 38.0-38.4°C, 2=Moderate: 38.5-38.9°C, 3=Severe: 39.0-40°C, and 4=Potentially life threatening:\>40°C. Only categories for which there was at least 1 participant are reported.

Percentage of Participants With Solicited Systemic AEs by Severity Within 7 Days After Dose 2 of PIZV or Placebo
Within 7 days after Dose 2 (Day 36)

Solicited systemic AEs included fever, headache, fatigue, malaise, arthralgia, and myalgia that occurred within 7 days of first vaccination. Solicited systemic AEs (headache, fatigue, malaise, arthralgia, and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was graded from 1 to 4 by severity; where 1=Mild: 38.0-38.4°C, 2=Moderate: 38.5-38.9°C, 3=Severe: 39.0-40°C, and 4=Potentially life threatening:\>40°C. Only categories for which there was at least 1 participant are reported.

Percentage of Participants Who Experienced at Least One Non-serious Unsolicited AE Within 28 Days After Dose 1 of PIZV or Placebo
Within 28 days after Dose 1 (Day 29)

An AE was defined as any untoward medical occurrence in participants administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.

Percentage of Participants Who Experienced at Least One Non-serious Unsolicited AE Within 28 Days After Dose 2 of PIZV or Placebo
Within 28 days after Dose 2 (Day 57)

An AE was defined as any untoward medical occurrence in a clinical investigation participants administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.

Percentage of Participants Who Experienced at Least One Serious Adverse Event (SAE) Within 28 Days After Dose 1 of PIZV or Placebo
Within 28 days after Dose 1 (Day 29)

A SAE was defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

Percentage of Participants Who Experienced at Least One SAE Within 28 Days After Dose 2 of PIZV or Placebo
Within 28 days after Dose 2 (Day 57)

A SAE was defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

Geometric Mean Titers (GMTs) of Neutralizing Antibody for Zika Virus (ZIKV) 28 Days After Dose 2 of PIZV or Placebo
28 days after Dose 2 (Day 57)

GMTs of neutralizing antibodies for ZIKV were measured by the Zika plaque reduction neutralization test (PRNT) test, by assessing the quantity of neutralizing antibodies that bind ZIKV in the assay. The assay results were reported as titers (reciprocal value of the dilution of the serum from the vaccinated individual that inhibits for 50% the plaque formation).

Secondary Endpoints
Percentage of Participants Who Experienced at Least One SAE During the Study
From day of first vaccination (Day 1) up to end of the study (Day 757)
GMTs of Neutralizing Antibody for ZIKV 28 Days After Dose 1 and 6 Months After Dose 2
28 days after Dose 1 (Day 29); 6 months after Dose 2 (Day 211)
GMTs of Neutralizing Antibody for ZIKV 12 Months and 24 Months After Dose 2 in Applicable Groups
12 months after Dose 2 (Day 393); 24 months after Dose 2 (Day 757)
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposePREVENTION
Treatment Arms
ArmTypeDescription
Flavivirus-naïve Cohort: PlaceboPLACEBO_COMPARATORPlacebo injection, intramuscular (IM), once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-naïve Cohort: PIZV 2 mcg (Low Dose)EXPERIMENTALPIZV 0.5 mL, 2 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-naïve Cohort: PIZV 5 mcg (Medium Dose)EXPERIMENTALPIZV 0.5 mL, 5 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-naïve Cohort: PIZV 10 mcg (High Dose)EXPERIMENTALPIZV 0.5 mL, 10 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-primed Cohort: PlaceboPLACEBO_COMPARATORPlacebo injection, IM, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-primed Cohort: PIZV 2 mcg (Low Dose)EXPERIMENTALPIZV 0.5 mL, 2 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-primed Cohort: PIZV 5 mcg (Medium Dose)EXPERIMENTALPIZV 0.5 mL, 5 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Flavivirus-primed Cohort: PIZV 10 mcg (High dose)EXPERIMENTALPIZV 0.5 mL, 10 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).
Interventions
NameTypeDescription
PlaceboDRUGPlacebo (normal saline (0.9% NaCl) IM injection.
PIZVBIOLOGICALPurified inactivated Zika virus vaccine with aluminum hydroxide adjuvant IM injection.
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Eligibility Criteria
Age Range18 Years — 49 Years
SexALL
Healthy VolunteersYes
Study Sites9

Inclusion Criteria: 1. Participants who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and eligibility screening tests (hematology, biochemistry and urinalysis) and clinical judgment of the investigator. Vital si...

Countries:United StatesPuerto Rico
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