A Study of Purified Inactivated Zika Virus Vaccine (PIZV) in Healthy Adults

NCT05469802 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: ZIK-201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to describe the side effects and immune response of a candidate vaccine that might protect against Zika. The vaccine called PIZV (purified inactivated Zika virus vaccine) is given by injection in two doses that are 28 days apart in healthy adults. Participants will receive PIZV or placebo and will be followed for 7 days after each dose and up to 6 months after dose 2.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (12)

• Percentage of Participants With Seropositivity for Neutralizing Antibodies Against Zika Virus at 28 Days Post Dose 2

  Seropositive participants are defined as participants with quantifiable (tested positive at or above the limit of quantitation \[LOQ\]) serum neutralizing anti-Zika virus (ZIKV) antibodies. Data will be reported for the overall study population (regardless of pre-vaccination flavivirus (FV) serostatus) and in FV naïve participants only.

  Within 28 days after Dose 2 (Day 57)

• Percentage of Participants With Seroconversion for Neutralizing Antibodies Against Zika Virus at 28 Days Post Dose 2

  Seroconversion is defined as the percentage of participants with either pre-vaccination titer \<LOQ and a post-vaccination titer ≥4xLOQ; or a pre-vaccination titer ≥LOQ and a 4-fold increase in titer post vaccination. Data will be reported for the overall study population (regardless of pre-vaccination FV serostatus) and in FV naïve participants only.

  Within 28 days after Dose 2 (Day 57)

• Geometric Mean Titers (GMTs) for Neutralizing Antibodies Against Zika Virus at 28 Days Post Dose 2

  GMTs for neutralizing antibodies against ZIKV will be measured by assessing the quantity of neutralizing antibodies that bind ZIKV. Data will be reported for the overall study population (regardless of pre-vaccination FV serostatus) and in FV naïve participants only.

  Within 28 days after Dose 2 (Day 57)

• Percentage of Participants With Solicited Local Injection Site Reactions for 7 Days After First Dose of Vaccination

  Solicited local AEs (at injection site) included pain/tenderness (mild: mild discomfort to touch, moderate: discomfort with movement, severe: significant discomfort at rest, potentially life-threatening: emergency room \[ER\] visit or hospitalization), erythema/redness (mild: 2.5 - 5 cm, moderate: 5.1 - 10 cm, severe: \> 10 cm, potentially life-threatening: necrosis or exfoliative dermatitis), and swelling/induration (mild: 2.5 - 5 cm and does not interfere with activity, moderate: 5.1 - 10 cm or interferes with activity, severe: \> 10 cm or prevents daily activity, potentially life-threatening: Necrosis). Data will be reported for the overall study population and in FV naïve participants only.

  Within 7 days after Dose 1 (Up to Day 7)

• Percentage of Participants With Solicited Local Injection Site Reactions for 7 Days After Second Dose of Vaccination

  Solicited local AEs (at injection site) included pain/tenderness (mild: mild discomfort to touch, moderate: discomfort with movement, severe: significant discomfort at rest, potentially life-threatening: ER visit or hospitalization), erythema/redness (mild: 2.5 - 5 cm, moderate: 5.1 - 10 cm, severe: \> 10 cm, potentially life-threatening: necrosis or exfoliative dermatitis), and swelling/induration (mild: 2.5 - 5 cm and does not interfere with activity, moderate: 5.1 - 10 cm or interferes with activity, severe: \> 10 cm or prevents daily activity, potentially life-threatening: Necrosis). Data will be reported for the overall study population and in FV naïve participants only.

  Within 7 days After Dose 2 (Days 29 to 35)

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7 Days After First Dose of Vaccination

  Solicited systemic AEs included fever, headache, fatigue, malaise, arthralgia, and myalgia that occurred within 7 days of first vaccination. Solicited systemic AEs will be graded from 1(mild) to 4(potentially life threatening) by severity. Fever: Grade 1(mild)= 38.0-38.4 degrees Celsius(°C)/100.4-101.1 degrees Fahrenheit (°F), Grade 2(moderate)=38.5-38.9°C/101.2-102.0°F, Grade 3(severe)=39.0-40°C/102.1-104°F, Grade 4 (potentially life threatening)=\>40°C/\>104°F. Headache, fatigue, malaise, arthralgia, and myalgia: Grade 1=no interference with activity, Grade 2=some interference with activity(Headache: repeated use of non-narcotic pain reliever\>24 hours or some interference with activity), Grade 3 =significant; prevents daily activity(Headache: significant; any use of narcotic pain reliever or prevents daily activity), and Grade 4=ER visit or hospitalization. Data will be reported for the overall study population and in FV naïve participants only.

  Within 7 days after Dose 1 (Up to Day 7)

• Percentage of Participants With Solicited Systemic AEs for 7 Days After Second Dose of Vaccination

  Solicited systemic AEs included fever, headache, fatigue, malaise, arthralgia, and myalgia that occurred within 7 days of first vaccination. Solicited systemic AEs will be graded from 1(mild) to 4(potentially life threatening) by severity. Fever: Grade 1(mild)= 38.0-38.4°C/100.4-101.1°F, Grade 2(moderate)=38.5-38.9°C/101.2-102.0°F, Grade 3(severe)=39.0-40°C/102.1-104°F, Grade 4 (potentially life threatening)=\>40°C/\>104°F. Headache, fatigue, malaise, arthralgia, and myalgia: Grade 1=no interference with activity, Grade 2=some interference with activity(Headache: repeated use of non-narcotic pain reliever\>24 hours or some interference with activity), Grade 3 =significant; prevents daily activity(Headache: significant; any use of narcotic pain reliever or prevents daily activity), and Grade 4=ER visit or hospitalization. Data will be reported for the overall study population and in FV naïve participants only.

  Within 7 days After Dose 2 (Days 29 to 35)

• Percentage of Participants With at Least One Unsolicited AE for 28 Days After First Dose of Vaccination

  An unsolicited AE is any AE reported by the participant that is either not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting solicited AE (ie, 7 days in total including the day of PIZV or placebo administration). Unsolicited AEs will be graded from 1 to 4 by severity, where Grade 1 (mild)= no interference with activity, Grade 2 (moderate)= some interference with activity, Grade 3 (severe)= significant; prevents daily activity, and Grade 4 (potentially life threatening)= ER visit or hospitalization. Data will be reported for the overall study population and in FV naïve participants only.

  Within 28 days after dose 1 (Up to Day 29)

• Percentage of Participants With at Least One Unsolicited AE for 28 Days After Second Dose of Vaccination

  An unsolicited AE is any AE reported by the participant that is either not specified as a solicited AE or is specified as a solicited AE but starts outside the period for reporting solicited AE (ie, 7 days in total including the day of PIZV or placebo administration). Unsolicited AEs will be graded from 1 to 4 by severity, where Grade 1 (mild)= no interference with activity, Grade 2 (moderate)= some interference with activity, Grade 3 (severe)= significant; prevents daily activity, and Grade 4 (potentially life threatening)= ER visit or hospitalization. Data will be reported for the overall study population and in FV naïve participants only.

  Within 28 days after dose 2 (Days 29 to 57)

• Percentage of Participants With at Least One Serious Adverse Event (SAE) Throughout the Entire Study Period

  An SAE will be 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 important medical 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. Data will be reported for the overall study population and in FV naïve participants only.

  From day of first vaccination (Day 1) up to end of the study (Day 211)

• Percentage of Participants With at Least One Adverse Events of Special Interest (AESI) Throughout the Entire Study Period

  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an PIZV or placebo; it does not necessarily have to have a causal relationship with PIZV or placebo administration. AESI is defined as an AE collected through the study period and entered in the eCRF by the investigator or designee within 24 hours of becoming aware of the event which includes new onset of or worsening of the following neurologic diseases: Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis, idiopathic peripheral facial nerve palsy (Bell's palsy), seizures including but not limited to febrile seizures and/or generalized seizures/convulsions, and anaphylaxis. Data will be reported for the overall study population and in FV naïve participants only.

  From day of first vaccination (Day 1) up to end of the study (Day 211)

• Percentage of Participants With at Least One Medically-Attended Adverse Event (MAAE) Throughout the Entire Study Period

  AE: any untoward medical occurrence in a clinical investigation participant administered PIZV or placebo; it does not necessarily have to have a causal relationship with trial vaccine administration. MAAEs is defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria. Data will be reported for the overall study population and in FV naïve participants only.

  From day of first vaccination (Day 1) up to end of the study (Day 211)

Secondary Outcomes (12)

• Percentage of Participants With Seropositivity for Neutralizing Antibodies Against Zika Virus

  Within 28 days after Dose 1 (Day 29) and 6 months after Dose 2 (Day 211)

• Percentage of Participants With Seropositivity for Neutralizing Antibodies Against Zika Virus in FV Exposed Participants

  Baseline (Day 1), within 28 days after Dose 1 (Day 29), 28 days after Dose 2 (Day 57) and 6 months after Dose 2 (Day 211)

• Percentage of Participants With Seroconversion for Neutralizing Antibodies Against Zika Virus

  Within 28 days after Dose 1 (Day 29) and 6 months after Dose 2 (Day 211)

• Percentage of Participants With Seroconversion for Neutralizing Antibodies Against Zika Virus in FV Exposed Participants

  Within 28 days after Dose 1 (Day 29), 28 days after Dose 2 (Day 57) and 6 months after Dose 2 (Day 211)

• Geometric Mean Titers (GMTs) for Neutralizing Antibodies Against Zika Virus

  Baseline (Day 1), within 28 days after Dose 1 (Day 29) and 6 months after Dose 2 (Day 211)

Study Arms (2)

PIZV 0.5 mL

EXPERIMENTAL

Participants will receive PIZV 0.5 mL injection, IM, once on Day 1 (first dose) and Day 29 (second dose).

Biological: Purified Inactivated Zika Virus Vaccine (PIZV)

Placebo 0.5 mL

PLACEBO COMPARATOR

Participants will receive a placebo injection, IM, once on Day 1 (first dose) and Day 29 (second dose).

Other: Placebo

Interventions

Purified Inactivated Zika Virus Vaccine (PIZV) BIOLOGICAL

PIZV vaccine with aluminium hydroxide adjuvant IM injection.

Also known as: TAK-426

PIZV 0.5 mL

Placebo OTHER

Placebo (normal saline (0.9% NaCl) IM injection.

Placebo 0.5 mL

Eligibility Criteria

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

You may qualify if:

• Healthy participants.
• Participants who can comply with trial procedures (including new trial technologies) and are available for the duration of follow-up.
• All females of childbearing potential must have a negative urine beta human chorionic gonadotropin (β-hCG) pregnancy test prior to receiving any dose.

You may not qualify if:

• Participants with past or current ZIKV infection by self-report.
• Participants with past or current dengue virus, yellow fever virus, Japanese encephalitis virus, tick-borne encephalitis virus or West Nile virus infection by self-report.
• Participants who have travelled to dengue and/or Zika endemic countries and US regions and territories\*, or who plan to travel to these countries/regions within 1 month prior to anticipated enrollment up to 1 month post dose 2.
• \*Centers for Disease Control and Prevention (CDC) website describes dengue/Zika endemic countries and US regions and territories.
• Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
• Participants with known or suspected impairment/alteration of immune function, including:
• Chronic use of oral or parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks / ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
• Receipt of immunomodulatory agents within 60 days prior to Day 1.
• Receipt of parenteral, epidural or intra-articular immunoglobulin preparation, blood products, and/or plasma derived products within 3 months prior to Day 1 or planned receipt during the full length of the trial. In addition, participants must be advised not to donate blood during the study period.
• Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
• Genetic immunodeficiency.
• Participants with known current or chronic hepatitis B and/or hepatitis C infections.
• Participants with abnormalities of splenic or thymic function.
• Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
• Participants with any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, insulin-dependent diabetes, cardiac, renal, hepatic or thyroid disease, uncontrolled hypertension, uncontrolled asthma).

Sponsors & Collaborators

• Takeda: lead

Study Sites (5)

CenExel Research Centers of America

Oakland Park, Florida, 33334, United States

Location

Velocity Clinical Research, Boise

Meridian, Idaho, 83642, United States

Location

AMR East Wichita, Formerly Heartland Associates East Wichita, an AMR company

Wichita, Kansas, 67207, United States

Location

AMR Lexington, Formerly Central Kentucky Research Associates, an AMR company

Lexington, Kentucky, 40509, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

Related Links

• To obtain more information about this study, click this link.

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 22, 2022
• Study Start: January 2, 2024
• Primary Completion: July 5, 2024
• Study Completion: July 5, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (5)