Phase 1 Trial to Assess the Safety and Immunogenicity of an Inactivated, Adjuvanted Whole Zika Virus Vaccine Candidate (VLA1601) in Healthy Adults

A Phase 1 Double-blind, Randomized, Dose Finding Clinical Trial With an Open-label run-in Part to Assess the Safety and Immunogenicity of an Inactivated, Adjuvanted Whole Zika Virus Vaccine Candidate (VLA1601) in Healthy Flavivirus-naïve Adults Aged 18 to 49 Years

This phase 1 clinical trial consists of an initial open-label sentinel run-in (n=25) and a randomized, double-blind, dose-finding (n=125) investigating three antigen dose levels (low, medium and high) of VLA1601 and bedside mixing of the low-dose formulation with one of the two additional adjuvants (CpG1018®, 3M-052-AF/AP 60-702). VLA1601 will be administered according to a two-dose regimen (i.e., on Day 1 and Day 29).

The primary objective of this trial is to assess the safety and tolerability of the vaccine candidate up to 7 days after each vaccination; and to assess the immune response induced by the vaccine candidate 28 days after the second vaccination. Additionally, safety and immune response of the vaccine candidate will be monitored throughout the trial.

Study Overview

• Status: Recruiting
• Conditions: Zika; Zika Virus Infection
• Intervention / Treatment: Biological: VLA1601; Biological: CpG 1018®; Biological: 3M-052-AF

Detailed Description

VLA1601 is a second generation, highly purified, inactivated, whole ZIKV vaccine candidate (adsorbed on aluminum hydroxide) designed for active immunization for the prevention of disease caused by the flavivirus ZIKV.

This phase 1 clinical trial consists of an initial open-label sentinel run-in (n=25) and a randomized, double-blind, dose-finding (n=125), investigating three antigen dose levels (low, medium and high) of VLA1601 and bedside mixing of the low-dose formulation with one of the two additional adjuvants (CpG1018®, 3M-052-AF/AP 60-702). VLA1601 will be administered according to a two-dose regimen (i.e., on Day 1 and Day 29). The screening period can last up to 21 days.

The trial will begin with the enrolment of 25 sentinel participants (5 participants in each of the 5 treatment arms) in a sequential open-label, staggered dose-escalation. The sentinel safety data will be closely monitored by the sponsor's Safety Review Committee (SRC). The SRC will decide on the start of the next treatment arm(s) during the run-in open-label part of the trial. An independent Data and Safety Monitoring Board (DSMB) will review safety data of all sentinels; upon favorable recommendation from the DSMB and sponsor decision, the trial will continue with the randomized part.

Approximately 125 participants will be randomized 1:1:1:1:1 into 5 treatment arms.

Primary objects include the assessment of safety and tolerability of VLA1601 up to 7 days following each vaccination and assessment of immunogenicity at 28 days post second vaccination.

Following a sponsor review of available safety and immunogenicity data up to 6 months after the second vaccination, the most favorable treatment arm(s) will be selected for an on-site visit at Day 395 for long-term safety and immunogenicity assessment. All other treatment arms will be followed only by phone-call for the Day 395 assessment of long-term safety.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: VP Clinical Development; Phone Number: +43 1 206200; Email: info@valneva.com
• Study Contact Backup: Name: Chief Medical Officer; Phone Number: +43 1 206200; Email: info@valneva.com

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Recruiting
      • Flourish Research
      • Contact: Rupal Trivedi, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Recruiting
      • Velocity Clinical Research
      • Contact: Frederick Raiser, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• 18 to 49 years of age
• BMI of ≥18.5 and <30 kg/m2
• generally healthy as determined by the investigator's clinical judgement based on medical history, physical examination, and screening laboratory tests.
• If trial participant is of childbearing potential: negative pregnancy test; employ adequate birth control measures up to Day 208.
• Male participant agrees to employ adequate birth control measures up to 90 days after last vaccination.

Key Exclusion Criteria:

Participant

• has a known history of the following flavivirus infection: Zika Virus (ZIKV), Japanese Encephalitis Virus (JEV), Dengue Virus (DENV), Yellow Fever Virus (YFV), West-Nile Virus (WNV), or Tick-Borne Encephalitis Virus (TBEV).
• received or has plans to receive a licensed flavivirus vaccine during the course of the trial.
• travelled within 4 weeks prior to trial enrollment or has plans to travel to areas (including within the US) with Zika virus (ZIKV), Japanese Encephalitis Virus (JEV), Dengue Virus (DENV) or Yellow Fever Virus (YFV) active transmission/circulation during the course of the trial .
• received active or passive immunization within 4 weeks prior or planned to get such vaccination after any trial-vaccination.
• presents with clinically significant abnormal laboratory values, as determined by the investigator.
• tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• has history of significant cardiovascular, respiratory (including asthma), metabolic, neurological (including Guillain-Barre syndrome [GBS]), hepatic, rheumatic, autoimmune, hematological, gastrointestinal, or renal disorder.
• with known or suspected defect of the immune system that would prevent an immune response to the vaccine.
• received immuno-suppressive therapy within 4 weeks prior to first vaccination. Radiation therapy or immunosuppressive cytotoxic drugs/ monoclonal antibodies in the previous 3 years.
• with a history of severe hypersensitivity reactions or anaphylaxis.
• with a history of any vaccine related contraindicating event .
• with acute febrile infections within two weeks prior to vaccination in this trial.
• donated blood within 4 weeks or received blood-derived products (e.g. plasma) within 12 weeks prior to vaccination in this trial or plans to donate blood or use blood products during the course of the trial.
• has a rash, dermatological condition or tattoos that would, in the opinion of the investigator, interfere with injection site reaction rating.
• presents with clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• is currently enrolled (ICF signed) or has participated in another clinical trial involving an investigational medicinal product (IMP) or device within 4 weeks prior to trial enrollment or is scheduled to participate in another clinical trial involving an IMP or investigational device during the course of this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLA1601 Low dose	Biological: VLA1601; 0.45mL (milliliter), Day 1 and 29
Experimental: VLA1601 Low dose + CpG 1018®	Biological: VLA1601; 0.45mL (milliliter), Day 1 and 29; Biological: CpG 1018®; CpG 1018® will be investigated in combination with VLA1601 Low dose
Experimental: VLA1601 Low dose + 3M-052-AF	Biological: VLA1601; 0.45mL (milliliter), Day 1 and 29; Biological: 3M-052-AF; 3M-052-AF will be investigated in combination with VLA1601 Low dose
Experimental: VLA1601 Medium dose	Biological: VLA1601; 0.45mL (milliliter), Day 1 and 29
Experimental: VLA1601 High dose	Biological: VLA1601; 0.45mL (milliliter), Day 1 and 29

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited Adverse Events	frequency of solicited AEs (injection site and systemic reactions)	7 days after each vaccination
Solicited Adverse Events	severity of solicited AEs (injection site and systemic reactions)	7 days after each vaccination
Neutralizing antibodies against ZIKA virus (ZIKV)	Geometric mean titer (GMT) for neutralizing antibodies against (ZIKV) determined by virus neutralization assay	Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited Adverse Events	frequency of solicited AEs (injection site and systemic reactions)	7 days after any vaccination
Solicited Adverse Events	severity of solicited AEs (injection site and systemic reactions)	7 days after any vaccination
Unsolicited AEs	frequency of unsolicited AEs	Day 57
Unsolicited AEs	severity of unsolicited AEs	Day 57
Vaccine-related unsolicited AEs	frequency of vaccine-related unsolicited AEs	Day 57
Vaccine-related unsolicited AEs	severity of vaccine-related unsolicited AEs	Day 57
Any AEs	severity of any AEs (including solicited and unsolicited AEs)	Day 395
Any AEs	frequency of any AEs (including solicited and unsolicited AEs)	Day 395
any vaccine-related AEs	severity of any vaccine-related AEs (including solicited and unsolicited AEs)	Day 395
Vaccine-related unsolicited AEs	frequency of vaccine-related AEs (including solicited and unsolicited AEs)	Day 395
Adverse Events of Special Interest (AESI)	severity of AESI	Day 395
Adverse Events of Special Interest (AESI)	frequency of AESI	Day 395
Vaccine-related Adverse Events of Special Interest (AESI)	frequency of vaccine-related AESI	Day 395
Vaccine-related Adverse Events of Special Interest (AESI)	severity of vaccine-related AESI	Day 395
Serious Adverse Events (SAE)	frequency of SAEs	Day 395
Serious Adverse Events (SAE)	severity of SAEs	Day 395
Vaccine-related Serious Adverse Events (SAE)	frequency of vaccine-related SAEs	Day 395
Vaccine-related Serious Adverse Events (SAE)	severity of vaccine-related SAEs	Day 395
ZIKV-specific neutralizing antibodies	Geometric Mean Titer (GMT) as determined by virus neutralization assay	up to Day 395 (including Day 1, 15, 29, 43, 208)
Seroconversion rate (SCR)	Rate of participants with seroconversion (cut-off of ZIKV-specific neutralizing antibody titer to be determined) compared to baseline determined by virus neutralization assay	up to Day 395 (including Day 1, 15, 29, 43, 208)
Geometric Mean Fold Increase (GMFI)	Geometric Mean Fold Increase compared to baseline determined by virus neutralization assay	up to Day 395 (including Day 1, 15, 29, 43, 208)

Collaborators and Investigators

• Sponsor: Valneva Austria GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 28, 2025

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: vaccine; Phase 1
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Mosquito-Borne Diseases; Zika Virus Infection; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; 1018 oligonucleotide; MEDI9197
• Other Study ID Numbers: VLA1601-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No