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Study to Demonstrate Consistency of Three Lots of a Live-attenuated Chikungunya Virus Vaccine Candidate in Healthy Adults

Phase 3
Completed
Conditions
Chikungunya Virus Infection
Interventions
Biological: Biological Vaccine VLA1553
Registration Number
NCT04786444
Lead Sponsor
Valneva Austria GmbH
Brief Summary

This was a prospective, randomized, double-blinded, multicenter Phase 3 clinical study investigating three Lots of VLA1553 at the final dose. Overall 409 healthy subjects aged 18 to 45 years were randomized into the study.

Detailed Description

This was a prospective, randomized, double-blinded, multicenter Phase 3 clinical study investigating three Lots of VLA1553. Overall 409 healthy subjects aged 18 to 45 years were randomized into the study, approximately136 subjects per VLA1553 Lot. Subjects were block-randomized in a 1:1:1 ratio into the three study arms to receive one of three Lots of VLA1553 as a single i.m. vaccination. The primary objective was to demonstrate Lot-to-Lot manufacturing consistency of VLA1553 28 days following the single vaccination.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
409
Inclusion Criteria
  1. 18 to 45 years of age 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 or vaccination, respectively
    3. agreed to employ adequate birth control measures for the first three months post-vaccination.
Exclusion Criteria
  1. CHIKV infection in the past (self-reported), 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 (and not symptom-free in the week prior to screening)
  3. Tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);
  4. Received another live virus vaccine within 28 days or inactivated vaccine within 14 days prior to vaccination in this study or plans 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. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws
  12. Pregnant, had plans to become pregnant during the first three months post-vaccination 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 use 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, could interfere with evaluation of study endpoints, or could 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VLA1553 Lot 1Biological Vaccine VLA1553-
VLA1553 Lot 3Biological Vaccine VLA1553-
VLA1553 Lot 2Biological Vaccine VLA1553-
Primary Outcome Measures
NameTimeMethod
Geometric Mean Titer (GMT) of CHIKV-specific Neutralizing Antibodies as Determined by Microneutralization (μPRNT) Assay in Subjects Who Tested Negative for CHIKV Antibodies at BaselineOn Day 29 after single vaccination
Secondary Outcome Measures
NameTimeMethod
Severity of Solicited Injection Site10 days post vaccination
Severity of Unsolicited Adverse Events (AEs) Within 28 Days Post-vaccinationup to Day 29
Severity of Any Adverse Event During the Entire Study Periodup to Month 6
Frequency of Any Adverse Event During the Entire Study Periodup to Month 6
Severity of Solicited Systemic Reactions10 days post vaccination
Frequency of Unsolicited Adverse Events (AEs) Within 28 Days Post-vaccinationup to Day 29
Severity of Any Adverse Event of Special Interest (AESI)within 2 to 21 days post-vaccination

AESI Definition:

The following cluster of symptoms suggestive of CHIKV infection with or without remissions or exacerbations received particular consideration:

1. Fever (≥38.0°C \[100.4°F\] measured orally) and

2. 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

3. Onset of symptoms 2 to 21 days after vaccination and

4. Duration of event ≥3 days.

Ongoing AESIs are monitored for entire study period

Immune Response as Measured by CHIKV-specific Neutralizing Antibody Titerson Day 8, 85 and Month 6
Frequency of Any Adverse Event of Special Interest (AESI)Within 2 to 21 Days Post-vaccination
Proportion of Subjects Reaching an at Least 4-fold, 8-fold, 16-fold or 64-fold Increase in CHIKV-specific Neutralizing Antibody Titer Compared to Baselineup to Month 6
Frequency of Solicited Injection Site10 days post vaccination
Frequency of Any Serious Adverse Event (SAE) During the Entire Study Periodup to Month 6
Proportion of Subjects With Seroprotective Levels for Baseline Negative Subjectson Day 8, 29, 85 and Month 6
Proportion of Subjects With Seroconversionon Day 29, Day 85 and Month 6
Fold Increase of CHIKV-specific Neutralizing Antibody Titers Compared to Baselineon Day 8, 29, 85 and Month 6
Frequency of Solicited Systemic Reactions10 days post vaccination

Trial Locations

Locations (12)

Dynamed Clinical Research

🇺🇸

Tomball, Texas, United States

AMR Lexington

🇺🇸

Lexington, Kentucky, United States

AMR Miami

🇺🇸

Coral Gables, Florida, United States

AMR Fort Myers

🇺🇸

Fort Myers, Florida, United States

AMR Knoxville

🇺🇸

Knoxville, Tennessee, United States

Rochester Clinical Research

🇺🇸

Rochester, New York, United States

St. Johns Center for Clinical Research

🇺🇸

Ponte Vedra, Florida, United States

Wr-Crcn, Llc

🇺🇸

Las Vegas, Nevada, United States

Walter Reed Amy Institute of Research

🇺🇸

Silver Spring, Maryland, United States

AMR Wichita West

🇺🇸

Wichita, Kansas, United States

Alliance for Multispecialty Research (AMR)

🇺🇸

Kansas City, Missouri, United States

Meridian Clinical Research

🇺🇸

Omaha, Nebraska, United States

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