Safety, Immunogenicity, and Dose Ranging Study of Inactivated Zika Virus Vaccine in Healthy Participants

NCT03343626 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: ZIK-101U1111-1201-5778
• Study Type: interventional
• Target: 271
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to describe the safety, tolerability and immunogenicity of two doses of purified inactivated Zika virus vaccine (PIZV) given 28 days apart. Three different vaccine doses containing different protein concentrations (2, 5 or 10 microgram \[mcg\]) each, will be given as 2 dose schedule to flavivirus naive and primed healthy adults. Participants will be followed for 7 days post each dose for tolerability and up to 6 months post dose 2 for safety. Immunogenicity assessment will be performed at 28 days post each dose and 6 months post dose 2. In addition, the selected dose group and control group will be followed till 24 months post dose 2 for safety and persistence of immunity.

Conditions

Virus, Zika; Zika Virus Disease; Flavivirus Infections; Healthy Participants

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With Solicited Local Injection Site Reactions by Severity Within 7 Days After Dose 1 of PIZV or Placebo

  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.

  Within 7 days after Dose 1 (Day 8)

• Percentage of Participants With Solicited Local Injection Site Reactions by Severity Within 7 Days After Dose 2 of PIZV or Placebo

  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.

  Within 7 days after Dose 2 (Day 36)

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

  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.

  Within 7 days after Dose 1 (Day 8)

• Percentage of Participants With Solicited Systemic AEs by Severity Within 7 Days After Dose 2 of PIZV or Placebo

  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.

  Within 7 days after Dose 2 (Day 36)

• Percentage of Participants Who Experienced at Least One Non-serious Unsolicited AE Within 28 Days After Dose 1 of PIZV or Placebo

  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.

  Within 28 days after Dose 1 (Day 29)

• Percentage of Participants Who Experienced at Least One Non-serious Unsolicited AE Within 28 Days After Dose 2 of PIZV or Placebo

  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.

  Within 28 days after Dose 2 (Day 57)

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

  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.

  Within 28 days after Dose 1 (Day 29)

• Percentage of Participants Who Experienced at Least One SAE Within 28 Days After Dose 2 of PIZV or Placebo

  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.

  Within 28 days after Dose 2 (Day 57)

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

  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).

  28 days after Dose 2 (Day 57)

Secondary Outcomes (6)

• 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)

• Percentage of Participants Seropositive for Neutralizing Antibodies Against PIZV 28 Days After Dose 1, 28 Days After Dose 2, and 6 Months After Dose 2

  28 days after Dose 1 (Day 29); 28 days after Dose 2 (Day 57); 6 months after Dose 2 (Day 211)

• Percentage of Participants Seropositive for PIZV 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)

Study Arms (8)

Flavivirus-naïve Cohort: Placebo

PLACEBO COMPARATOR

Placebo injection, intramuscular (IM), once on Day 1 (first dose) and Day 29 (second dose).

Drug: Placebo

Flavivirus-naïve Cohort: PIZV 2 mcg (Low Dose)

EXPERIMENTAL

PIZV 0.5 mL, 2 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Flavivirus-naïve Cohort: PIZV 5 mcg (Medium Dose)

EXPERIMENTAL

PIZV 0.5 mL, 5 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Flavivirus-naïve Cohort: PIZV 10 mcg (High Dose)

EXPERIMENTAL

PIZV 0.5 mL, 10 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Flavivirus-primed Cohort: Placebo

PLACEBO COMPARATOR

Placebo injection, IM, once on Day 1 (first dose) and Day 29 (second dose).

Drug: Placebo

Flavivirus-primed Cohort: PIZV 2 mcg (Low Dose)

EXPERIMENTAL

PIZV 0.5 mL, 2 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Flavivirus-primed Cohort: PIZV 5 mcg (Medium Dose)

EXPERIMENTAL

PIZV 0.5 mL, 5 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Flavivirus-primed Cohort: PIZV 10 mcg (High dose)

EXPERIMENTAL

PIZV 0.5 mL, 10 mcg antigen, IM injection, once on Day 1 (first dose) and Day 29 (second dose).

Biological: PIZV

Interventions

Placebo DRUG

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

Flavivirus-naïve Cohort: Placebo; Flavivirus-primed Cohort: Placebo

PIZV BIOLOGICAL

Purified inactivated Zika virus vaccine with aluminum hydroxide adjuvant IM injection.

Also known as: TAK-426

Flavivirus-naïve Cohort: PIZV 10 mcg (High Dose); Flavivirus-naïve Cohort: PIZV 2 mcg (Low Dose); Flavivirus-naïve Cohort: PIZV 5 mcg (Medium Dose); Flavivirus-primed Cohort: PIZV 10 mcg (High dose); Flavivirus-primed Cohort: PIZV 2 mcg (Low Dose); Flavivirus-primed Cohort: PIZV 5 mcg (Medium Dose)

Eligibility Criteria

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

You may qualify if:

• 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 signs must be within normal limits (ie, below Grade 1 as specified in the Food and Drug Administration \[FDA\] Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers). Screening tests must be within normal limits or not be above Grade 1 as defined in the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers.
• Participants who can comply with trial procedures and are available for the duration of follow-up.
• All female participants must be willing to undergo serum beta human chorionic gonadotropin (B-hCG) pregnancy test and must test negative by urine pregnancy test prior to each study vaccination.

You may not qualify if:

• Participants and participants' partners with confirmed Zika virus (ZIKV) infection by self-report.
• Traveling to flavivirus endemic countries or flavivirus endemic regions of the United States (US) or US territories\*, within 4 weeks prior to screening or planned travel through to Visit 6 (applicable only to participants to be enrolled into the flavivirus naïve cohort).
• a. Centers for Disease Control and Prevention (CDC) website define the information about the flavivirus endemic countries and US regions and territories.
• Known hypersensitivity or allergy to any of the vaccine candidate components (including excipients of the investigational vaccine or placebo).
• Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (example, Guillain-Barré syndrome).
• Known or suspected impairment/alteration of immune function, including:
• Chronic use of oral steroids (equivalent to 20 milligram per day \[mg/day\] prednisone greater than or equal to \[\>=\] 12 weeks / \>= 2 milligram per kilogram \[mg/kg\] body weight / day prednisone \>= 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
• Receipt of 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.
• Receipt of immunostimulants 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 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.
• Has known current or chronic hepatitis B and/or hepatitis C infections.
• Has abnormalities of spleen or thymic function.
• Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

Sponsors & Collaborators

• Takeda: lead

Study Sites (9)

Clinical Research of South Florida

Coral Gables, Florida, 33134, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

AppleMed Research

Miami, Florida, 33155, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Regional Clinical Research Inc.

Endwell, New York, 13760, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

Tekton Research

Austin, Texas, 78745, United States

Location

Puerto Rico Clinical and Translational Research Consortium

San Juan, PR, 00936, Puerto Rico

Location

Ponce Medical School Foundation

Santurce, PR, 00909, Puerto Rico

Location

Related Publications (2)

• Acosta CJ, Diaz C, Nordio F, Han HH, Moss KJ, Bohning K, Kumar P, Liu M, Patel H, Pacciarini F, Mwangi V, Walter E, Powell TD, El Sahly HM, Baldwin WR, Santangelo J, Anderson EJ, Dubin G. Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection. J Infect Dis. 2023 May 29;227(11):1303-1312. doi: 10.1093/infdis/jiac482.

  PMID: 36484441 DERIVED

• Han HH, Diaz C, Acosta CJ, Liu M, Borkowski A. Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in healthy adults: an observer-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021 Sep;21(9):1282-1292. doi: 10.1016/S1473-3099(20)30733-7. Epub 2021 May 18.

  PMID: 34019802 DERIVED

MeSH Terms

Conditions

Zika Virus Infection; Flavivirus Infections

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: November 13, 2017
• First Posted: November 17, 2017
• Study Start: November 13, 2017
• Primary Completion: December 28, 2018
• Study Completion: November 24, 2020
• Last Updated: February 11, 2022
• Results First Posted: February 11, 2022

Record last verified: 2021-11

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

PR (2); US (7)