A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects.

NCT02963909 | Completed Phase 1 FDA Drug

• 1 other identifier: 16-0062
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 study to evaluate two doses of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) administered 28 days apart. The study will enroll 75 flavivirus naïve healthy adult subjects into 3 equal groups sequentially. Each group will include 20 ZPIV recipients and 5 placebo recipients. Group 1 will receive two ZPIV or placebo doses 28 days apart. Those in Group 1 who consent to a third ZPIV dose will receive 5.0 mcg dose of ZPIV or placebo administered IM on Day 224. Group 2 subjects will receive a two-dose regimen of IXIARO® 28 days apart; two ZPIV or placebo doses three months later 28 days apart. Those in Group 2 who consent to a third ZPIV dose will receive it on Day 336. Group 3 subjects will receive one dose of YF-VAX® followed three months later by two ZPIV or placebo doses 28 days apart. Those in Group 3 who consent to a third ZPIV dose will receive it on Day 308. In each group, those who do not agree to receive the third ZPIV dose will be followed based on the schedule. The primary objectives are: 1) To evaluate the safety and reactogenicity of a two-dose homologous prime boost regimen of ZPIV among flavivirus-naïve, YF-VAX® primed, and IXIARO® primed subjects; 2) To evaluate the safety and reactogenicity of a third dose of ZPIV in consenting subjects.

Conditions

Zika Virus Infection

Keywords

Adjuvant; Alum; Inactivated; Purified; Vaccine; Virus; Zika

Outcome Measures

Primary Outcomes (8)

• Occurrence of SAEs, new onset medical conditions, and AESIs

  From Day 1 to Day 658

• Occurrence of solicited local AEs

  7 days following each ZPIV dose

• Occurrence of solicited systemic AEs

  7 days following each ZPIV dose

• Occurrence of unsolicited AEs

  28 days following each ZPIV dose

• Relationship of unsolicited AEs to vaccination

  28 days following each ZPIV dose

• Severity of solicited local AEs

  7 days following each ZPIV dose

• Severity of solicited systemic AEs

  7 days following each ZPIV dose

• Severity of unsolicited AEs

  28 days following each ZPIV dose

Secondary Outcomes (20)

• Anti- ZIKV NAbs GMTs by group in subjects who consent to two doses of ZPIV

  28 days after each ZPIV dose

• Anti- ZIKV NAbs GMTs by group in subjects who consent to two doses of ZPIV

  Days 112, 196, 280 and 364 after initial ZPIV dose

• Anti- ZIKV NAbs GMTs overall

  28 days after each ZPIV dose

• Anti- ZIKV NAbs GMTs overall

  Days 112, 196, 280 and 364 after initial ZPIV dose

• Anti- ZIKV NAbs seroconversion rates by group in subjects who consent to two doses of ZPIV

  28 days after each ZPIV dose

Study Arms (3)

ZPIV in Flavivirus-naïve Subjects

EXPERIMENTAL

Two doses of 5.0mcg ZPIV or placebo on Days 1 and 29. N=20 ZPIV, N=5 placebo. Subjects who consent to a third ZPIV dose will receive a 5.0 mcg of ZPIV or placebo on Day 224

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

ZPIV in JEV (IXIARO®)

EXPERIMENTAL

Two 0.5mL doses of IXIARO® (Valneva) Days 1 and 29 followed by two ZPIV or placebo doses will be administered on Days 112 and 140. N=20 ZPIV, N=5 placebo. Subjects who consent to a third ZPIV dose will receive it on Day 336

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

ZPIV in YFV (YF-VAX®)

EXPERIMENTAL

One 0.5mL dose of YF-VAX® (Sanofi Pasteur) on Day 1 followed by two ZPIV or placebo doses on Days 84 and 112. N=20 ZPIV, N=5 placebo. Subjects who consent to a third ZPIV dose will receive it on Day 308

Other: Placebo; Biological: YF Vax 17D Strain; Biological: Zika Virus Purified Inactivated Vaccine (ZPIV)

Interventions

IXIARO BIOLOGICAL

An inactivated vaccine indicated for active immunization for the prevention of disease caused by Japanese encephalitis virus (JEV).

ZPIV in JEV (IXIARO®)

Placebo OTHER

0.9% Sodium Chloride 5 mcg

ZPIV in Flavivirus-naïve Subjects; ZPIV in JEV (IXIARO®); ZPIV in YFV (YF-VAX®)

YF Vax 17D Strain BIOLOGICAL

A stabilised Yellow Fever Vaccine (Live) that is an injectable suspension of the attenuated 17D strain of yellow fever virus. The vaccine is injected by the subcutaneous route.

ZPIV in YFV (YF-VAX®)

Zika Virus Purified Inactivated Vaccine (ZPIV) BIOLOGICAL

Zika Virus Purified Inactivated Vaccine with aluminum hydroxide adjuvant.

ZPIV in Flavivirus-naïve Subjects; ZPIV in JEV (IXIARO®); ZPIV in YFV (YF-VAX®)

Eligibility Criteria

• Age: 18 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 ages of 18 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 be 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 40 days before day 1.
• Acceptable clinical laboratory parameters include no more than Grade 1 on toxicity scale.
• White Blood Cell (WBC), Hemoglobin, and platelet count will be reported as part of the Complete Blood Count (CBC). These labs will be graded according to the toxicity scale. Other results included on the CBC panel will not be graded. They will be reviewed by an investigator who will determine clinical significance and may be used to determine additional workup.
• Sodium, potassium, blood urea nitrogen (BUN), creatinine, random glucose, total protein, albumin, calcium, AST, ALT, total bilirubin, and alkaline phosphatase will be reported as part of the Complete Metabolic Panel (CMP). These labs will be graded according to the toxicity scale. Other results included on the CMP panel will not be graded. They will be reviewed by an investigator who will determine clinical significance and may be used to determine additional workup.
• Note: If laboratory screening tests are out of acceptable range, repeat of screening tests is permitted one time, provided there is an alternative explanation for the out of range value.
• Must be in good health based on the investigator's clinical judgment when considering findings from past medical history, medication use, vital signs, and an abbreviated physical examination.

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 urine 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 sterile 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 at least 60 days after the last vaccination.
• 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). 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). Have one male sex partner who has had a vasectomy \>/=3 months prior. Male partner with barrier protection plus the use of vaginal spermicide. Practice abstinence defined as refraining from heterosexual intercourse from 30 days before first vaccination until at least 60 days after last ZPIV vaccination.
• Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening period until at least 60 days after receiving the last ZPIV vaccination.
• Has plans to become pregnant, or is currently pregnant or breastfeeding.
• Has plans to travel to an area with active ZIKV, DENV, YFV, or JEV transmission during the study or returned from an endemic area with these diseases within 30 days of screening.
• NOTE: Refer to Centers for Disease Control and Prevention (CDC) website for areas with active ZIKV transmission: http://www.cdc.gov/zika/geo
• Has history of vaccination with a licensed or investigational flavivirus vaccine or reportedly diagnosed with a flavivirus infection or disease. Includes subject's verbal history of vaccination or disease with any of the following flaviviruses:
• YFV: YF-VAX®, Stamaril, or Bio-Manguinhos YF vaccine;
• JEV: investigational vaccine or licensed vaccine (IXIARO®);
• DENV: investigational vaccine or Sanofi Pasteur newly licensed vaccine;
• WNV: investigational vaccine;

Sponsors & Collaborators

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

Study Sites (1)

Walter Reed Army Institute of Research - Clinical Trials Center

Silver Spring, Maryland, 20910-7500, United States

Location

Related Publications (2)

• Koren MA, Lin L, Eckels KH, De La Barrera R, Dussupt V, Donofrio G, Sondergaard EL, Mills KT, Robb ML, Lee C, Adedeji O, Keiser PB, Curley JM, Copeland NK, Crowell TA, Hutter JN, Hamer MJ, Valencia-Ruiz A, Darden J, Peel S, Amare MF, Mebrahtu T, Costanzo M, Krebs SJ, Gromowski GD, Jarman RG, Thomas SJ, Michael NL, Modjarrad K. Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial. Lancet Infect Dis. 2023 Oct;23(10):1175-1185. doi: 10.1016/S1473-3099(23)00192-5. Epub 2023 Jun 27.

  PMID: 37390836 DERIVED

• Modjarrad K, Lin L, George SL, Stephenson KE, Eckels KH, De La Barrera RA, Jarman RG, Sondergaard E, Tennant J, Ansel JL, Mills K, Koren M, Robb ML, Barrett J, Thompson J, Kosel AE, Dawson P, Hale A, Tan CS, Walsh SR, Meyer KE, Brien J, Crowell TA, Blazevic A, Mosby K, Larocca RA, Abbink P, Boyd M, Bricault CA, Seaman MS, Basil A, Walsh M, Tonwe V, Hoft DF, Thomas SJ, Barouch DH, Michael NL. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials. Lancet. 2018 Feb 10;391(10120):563-571. doi: 10.1016/S0140-6736(17)33106-9. Epub 2017 Dec 5.

  PMID: 29217375 DERIVED

MeSH Terms

Conditions

Zika Virus Infection; Virus Diseases

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: November 1, 2016
• Primary Completion: October 30, 2018
• Study Completion: October 30, 2018
• Last Updated: April 22, 2024

Record last verified: 2017-08-01

Locations

US (1)