Pivotal Study to Evaluate Safety and Immunogenicity of a Live-Attenuated Chikungunya Virus Vaccine Candidate in Adults

Chikungunya Virus Infection Clinical Trial

Official title:

A Multicenter, Randomized, Placebo-Controlled, Double-Blinded Pivotal Study To Evaluate Safety And Immunogenicity Of A Live-Attenuated Chikungunya Virus Vaccine Candidate In Adults Aged 18 Years And Above

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04546724
• Other study ID #: VLA1553-301
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2020
• Est. completion date: October 15, 2021

Study information

• Verified date: June 2023
• Source: Valneva Austria GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a prospective, randomized, double-blinded, multicenter, pivotal clinical study evaluating the final dose of VLA1553 (1 x10E4 TCID50 per dose) in comparison to a placebo control. The final dose of VLA1553 or control was administered as single immunization on Day 1. Overall, 4.128 male and female subjects aged 18 years and above were randomized into the study.

Description:

This was a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study and 4.128 participants aged 18 years or above were randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo was administered as a single intramuscular immunization. Subjects in this study were stratified into two age strata of 18 to 64 years and 65 years of age or above. The primary objective of the study was to evaluate the immunogenicity and safety of the final dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset included the proportion of subjects with seroprotective neutralizing CHIKV antibody titers above a surrogate threshold indicative of protection. The surrogate of protection reasonably likely to predict clinical benefit has been established in non-human primate passive transfer studies using human sera from the Phase 1 study and was supported by sero-epidemiological studies. Safety data collection and immunogenicity were assessed until Month 6.

The first enrolled and randomized 501 subjects comprised the immunogenicity subset.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4128
• Est. completion date: October 15, 2021
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 18 years of age or above on the Day of screening

2. able to provide informed consent

3. generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests

4. for women of childbearing potential:

1. practiced an adequate method of contraception during 30 days before screening

2. negative serum or urine pregnancy test at screening

3. agreed to employ adequate birth control measures for the first three months post-vaccination.

Main Exclusion Criteria:

1. CHIKV infection in the past, including suspected CHIKV infection; was taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or had participated in a clinical study involving an investigational CHIKV vaccine

2. acute or recent infection

3. Subject tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);

4. live virus vaccine within 28 days or inactivated vaccine within 14 days prior to vaccination in this study or planned to receive a vaccine within 28 days or 14 days after vaccination, respectively

5. abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator which pose a risk for participation in the study

6. medical history of or currently had acute or progressive, unstable or uncontrolled clinical conditions that posed a risk for participation in the study

7. history of immune-mediated or clinically relevant arthritis / arthralgia

8. history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there had been surgical excision or treatment more than 5 years ago that was considered to have achieved a cure, the subject could be enrolled.

9. known or suspected defect of the immune system, such as subjects with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to vaccination.

10. history of any vaccine related contraindicating event (e.g., anaphylaxis, allergy to components of the candidate vaccine, other known contraindications)

11. with clinical conditions representing a contraindication to intramuscular vaccination and blood draws

12. pregnant or lactating at the time of enrollment

13. Donation of blood, blood fractions or plasma within 30 days or received blood-derived products (e.g. plasma) within 90 days prior to vaccination in this study or planned to donate blood or used blood products until Day 180 of the study

14. rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating

15. known or suspected problem with alcohol or drug abuse as determined by the Investigator

16. any condition that, in the opinion of the Investigator, could compromise the subjects well-being, interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;

17. committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities)

18. Participation in another clinical study involving an investigational medicinal product (IMP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study

19. member of the team conducting the study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the Investigator or site personnel conducting the study.

Related Conditions & MeSH terms

• Chikungunya Fever
• Chikungunya Virus Infection
• Virus Diseases

Intervention

Biological:
• VLA1553
Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate; 1x10E4 TCID50 per dose
• Placebo
Single intramuscular vaccination on Day 1 with Phosphate-Buffered Saline (PBS) as placebo

Locations

Country	Name	City	State
United States	Synexus - Anderson	Anderson	South Carolina
United States	Vitalink Research - Anderson	Anderson	South Carolina
United States	Tekton Research - Beaumont	Beaumont	Texas
United States	PanAmerican Clinical Research - US Headquarter	Brownsville	Texas
United States	Velocity Clinical Research - Austin	Cedar Park	Texas
United States	Accelerated Enrollment Solutions (AES)	Chandler	Arizona
United States	Accelerated Enrollment Solutions (AES)	Chicago	Illinois
United States	Velocity Clinical Research, Chula Vista	Chula Vista	California
United States	Accelerated Enrollment Solutions (AES)	Cincinnati	Ohio
United States	Accel Research Sites - DeLand	DeLand	Florida
United States	Alliance for Multispecialty Research (AMR)	El Dorado	Kansas
United States	Meridian Clinical Research	Endwell	New York
United States	Meridian Clinical Research - Grand Island	Grand Island	Nebraska
United States	ELITE Research Network (ELITE)	Hallandale Beach	Florida
United States	Alliance for Multispecialty Research (AMR)	Kansas City	Missouri
United States	Alliance for Multispecialty Research (AMR)	Knoxville	Tennessee
United States	Alliance for Multispecialty Research (AMR)	Las Vegas	Nevada
United States	Alliance for Multispecialty Research (AMR)	Lexington	Kentucky
United States	ELITE Research Network (ELITE)	Little Rock	Arkansas
United States	Meridien Research - Maitland	Maitland	Florida
United States	Velocity Clinical Research - Medford	Medford	Oregon
United States	Accelerated Enrollment Solutions (AES)	Melbourne	Florida
United States	ELITE Research Network (ELITE)	Meridian	Idaho
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Lucas Research	Morehead City	North Carolina
United States	AMR - New Orleans - Center for Clinical Research	New Orleans	Louisiana
United States	Alliance for Multispecialty Research (AMR)	Newton	Kansas
United States	Alliance for Multispecialty Research (AMR)	Norfolk	Virginia
United States	ELITE Research Network (ELITE)	North Miami Beach	Florida
United States	ELITE Research Network (ELITE)	Oklahoma City	Oklahoma
United States	Accelerated Enrollment Solutions (AES)	Omaha	Nebraska
United States	Platinum Research Network (Platinum)	Omaha	Nebraska
United States	Accelerated Enrollment Solutions (AES)	Peoria	Illinois
United States	Accelerated Enrollment Solutions (AES)	Phoenix	Arizona
United States	Research Your Health, LLC	Plano	Texas
United States	Jacksonville Center for Clinical Research, LTD dba St. Johns Center for Clinical Research	Ponte Vedra	Florida
United States	Rochester Clinical Research	Rochester	New York
United States	Accelerated Enrollment Solutions (AES)	San Diego	California
United States	Alliance for Multispecialty Research (AMR)	Tempe	Arizona
United States	Synexus - The Villages	The Villages	Florida
United States	ELITE Research Network (ELITE)	Tomball	Texas
United States	ELITE Research Network (ELITE)	West Jordan	Utah
United States	Alliance for Multispecialty Research (AMR)	Wichita	Kansas
United States	ELITE Research Network (ELITE)	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Valneva Austria GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination	Seroprotection rate, based on a surrogate of protection agreed with FDA; Assay used for analysis was based on µPRNT (Micro Plaque Reduction Neutralization Test). Participants at pre-selected sites were included, if they had available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.	on Day 29 after single vaccination
Secondary	CHIKV-specific Neutralizing Antibody Titers	CHIKV-specific Neutralizing Antibody Titers on Day 8, and Day 29 Postvaccination as Determined by µPRNT ( (Micro Plaque Reduction Neutralization Test) Assay	Until Day 180
Secondary	Number of Participants With Seroprotective CHIKV Antibody Level	Seroprotection rate, based on a surrogate of protection agreed with FDA Seroprotective CHIKV Antibody Level Defined as µPRNT (Micro Plaque Reduction Neutralization Test) for Baseline Negative Subjects	Until Day 180
Secondary	Number of Participants With Seroconversion	Seroconversion was defined as CHIKV-specific neutralizing antibody titer of = 20 based on µPRNT (Micro Plaque Reduction Neutralization Test) for baseline negative subjects	Until Day 180
Secondary	Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline	Fold Change of CHIKV-specific Neutralizing Antibody Titers Determined by µPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline	until Day 180
Secondary	Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline	Number of Participants Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold change of CHIKV-specific Neutralizing Antibody Titers Determined by µPRNT ( (Micro Plaque Reduction Neutralization Test) as compared to baseline	until Day 180
Secondary	Unsolicited AEs	Number of Participants with Unsolicited Adverse Events	Until Day 29
Secondary	Solicited Injection Site AEs	Number of Participants with solicited injection site reactions	within 10 days post-vaccination
Secondary	Solicited Systemic AEs	Number of Participants with solicited systemic reactions	within 10 days post-vaccination
Secondary	Adverse Events	Number of Participants with any Adverse Events	until Day 180
Secondary	Related Adverse Events	Number of Participants with any related Adverse Events	until Day 180
Secondary	Serious Adverse Event	Number of Participants with any Serious Adverse Events	until Day 180
Secondary	Related Serious Adverse Event	Number of Participants with any Related Serious Adverse Events	until Day 180
Secondary	Adverse Event of Special Interest	Number of Participants with any Adverse Event of Special Interest; AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: Fever (=38.0°C [100.4°F] measured orally) and; Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus [foot plant] and edema of the face and extremities), polyadenopathies; and; Onset of symptoms 2 to 21 days after vaccination and; Duration of event =3 days.	within 21 days post-vaccination
Secondary	Related Adverse Event of Special Interest	Number of Participants with any Related Adverse Event of Special Interest; AESI Definition: The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration: Fever (=38.0°C [100.4°F] measured orally) and; Acute (poly)arthralgia/arthritis most frequently in the extremities (wrists, ankles, and phalanges, often symmetric), back pain and/or neurological symptoms (e.g. confusion, optic neuritis, meningoencephalitis, or polyneuropathy) and/or cardiac symptoms (e.g. myocarditis) or One or more of the following signs and symptoms: macular to maculopapular rash (sometimes with cutaneous pruritus [foot plant] and edema of the face and extremities), polyadenopathies; and; Onset of symptoms 2 to 21 days after vaccination and; Duration of event =3 days.	within 21 days post-vaccination