NCT02963909

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.

A Phase 1, First-in-Human, Double-blinded, Randomized, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of an Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) in Healthy Flavivirus-Naïve and Flavivirus-Primed Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

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.

Detailed description

This study is a single-center, double-blinded, placebo-controlled, first-in-human, Phase 1 study to evaluate the safety, reactogenicity, and immunogenicity of two doses of alum adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) administered 28 days apart. The study will enroll 75 flavivirus naïve healthy male and non-pregnant, non-breastfeeding female adult subjects (ages 18-49, inclusive) into 3 equal groups sequentially, starting with Group 1 followed by Group 2 and then Group 3. Screening will occur within 40 days of first vaccination. Each group will include 20 ZPIV recipients and 5 placebo recipients. Two sentinel subjects from Group 1 will be enrolled first and will receive ZPIV in an open-label fashion first. The next 23 subjects (18 ZPIV, 5 placebo) will be randomized into Group 1. This will be followed by the randomization of 25 subjects into Group 2 (JE priming). The remaining 25 subjects to enroll will be randomized into Group 3 (YF priming). Group 1 subjects will receive two 5.0 mcg doses of ZPIV or placebo administered IM on Days 1 and 29. 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® (Valneva) 28 days apart; two ZPIV or placebo doses will be administered three months later IM 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® (Sanofi Pasteur) followed three months later by two ZPIV or placebo doses administered IM 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. The secondary objectives are: 1) To evaluate the quantitative humoral immune response at 28 days after the first and second ZPIV administration, and 112, 196, 280, and 364 days after the first ZPIV administration for each of the three groups in subjects who consent to two doses of ZPIV; 2) To evaluate the quantitative humoral immune response at 28 days after the first and second ZPIV administration, and 112, 196, 224 days after the first ZPIV administration and at 28, 84, and 168 days after the third ZPIV administration for Group 1 subjects who consent to third dose; 3) To evaluate the quantitative humoral immune response at 28 days after the first and second ZPIV administration, and 112, 224 days after the first ZPIV administration and at 28, 84, and 168 days after the third ZPIV administration for Group 2 and 3 subjects who consent to third dose.

Conditions

• Zika Virus Infection

Interventions

Type	Name	Description
BIOLOGICAL	IXIARO	An inactivated vaccine indicated for active immunization for the prevention of disease caused by Japanese encephalitis virus (JEV).
OTHER	Placebo	0.9% Sodium Chloride 5 mcg
BIOLOGICAL	YF Vax 17D Strain	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.
BIOLOGICAL	Zika Virus Purified Inactivated Vaccine (ZPIV)	Zika Virus Purified Inactivated Vaccine with aluminum hydroxide adjuvant.

Timeline

• Start date: 2016-11-01
• Primary completion: 2018-10-30
• Completion: 2018-10-30
• First posted: 2016-11-15
• Last updated: 2024-04-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study