An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) (VALOR)

• ClinicalTrials.gov Identifier: NCT05477524
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2022
• Last Update Posted: March 25, 2024
• Sponsor: Pfizer
• Collaborator: Valneva Austria GmbH
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: July 5, 2022
• First Posted Date: July 28, 2022
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: August 4, 2022
• Estimated Primary Completion Date: December 26, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 7, 2023)

• Relative risk reduction of confirmed Lyme disease cases in the VLA15 group compared to the placebo group [ Time Frame: Beginning 1 month after receiving the booster dose (28 days after receiving the booster dose through the end of the Lyme disease season following the booster dose (end of October)). ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Percentage of participants reporting local reactions [ Time Frame: Within 7 days following each study intervention administration ]
• Percentage of participants reporting systemic events [ Time Frame: Within 7 days following each study intervention administration ]
• Percentage of participants reporting adverse events (AEs) [ Time Frame: Through 1 month following each study intervention administration ]
• Percentage of participants reporting newly diagnosed chronic medical conditions (NDCMCs) [ Time Frame: Through study completion, up to approximately 30 months. ]
• Percentage of participants reporting serious adverse events (SAEs) [ Time Frame: Through study completion, up to approximately 30 months. ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 1 to Lot 2 [ Time Frame: At 1 month after completion of the primary series and the booster dose ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 1 to Lot 3 [ Time Frame: At 1 month after completion of the primary series and the booster dose ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 2 to Lot 3 [ Time Frame: At 1 month after completion of the primary series and the booster dose ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) [ Time Frame: At 1 month after completion of the booster dose ]
  Immunobridging objective to determine non-inferiority between 5-17 year old and 18-44 year old participant strata.

Original Primary Outcome Measures (submitted: July 25, 2022)

• Relative risk reduction of confirmed Lyme disease cases in the VLA15 group compared to the placebo group [ Time Frame: In the Lyme disease season beginning 1 month after completing the primary series (28 days after completion of the primary series until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Relative risk reduction of confirmed Lyme disease cases in the VLA15 group compared to the placebo group [ Time Frame: In the Lyme disease season beginning 1 month after receiving the booster dose (28 days after completion of the booster dose until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Percentage of participants reporting prompted local reactions [ Time Frame: Within 7 days following each study intervention administration ]
• Percentage of participants reporting prompted systemic events [ Time Frame: Within 7 days following each study intervention administration ]
• Percentage of participants reporting adverse events (AEs) [ Time Frame: Through 1 month following each study intervention administration ]
• Percentage of participants reporting newly diagnosed chronic medical conditions (NDCMCs) [ Time Frame: Through study completion, up to approximately 30 months. ]
• Percentage of participants reporting serious adverse events (SAEs) [ Time Frame: Through study completion, up to approximately 30 months. ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 1 to Lot 2 [ Time Frame: At 1 month after completion of the primary series ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 1 to Lot 3 [ Time Frame: At 1 month after completion of the primary series ]
• Geometric mean ratio (GMR) of anti-OspA titers for each serotype (ST1-ST6) for Lot 2 to Lot 3 [ Time Frame: At 1 month after completion of the primary series ]

Current Secondary Outcome Measures (submitted: July 7, 2023)

• Vaccine efficacy among participants enrolled from North American sites [ Time Frame: Through the end of the Lyme disease season beginning 1 month after receiving the booster dose (28 days after completion of the booster dose until end of October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Vaccine efficacy among participants after primary series [ Time Frame: Through the end of the Lyme disease season beginning 1 month after completing the primary series (28 days after completion of the primary series until end of October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee

Original Secondary Outcome Measures (submitted: July 25, 2022)

• Relative risk reduction of Lyme disease-specific seroconversion in otherwise-undiagnosed Lyme disease cases in the VLA15 group compared to the placebo group [ Time Frame: In the Lyme disease season beginning 1 month after completing the primary series (28 days after completion of the primary series until 31 October) ]
  Nonvaccine-antigen seroconversion as measured at the central laboratory
• Relative risk reduction of Lyme disease-specific seroconversion in otherwise-undiagnosed Lyme disease cases in the VLA15 group compared to the placebo group [ Time Frame: In the Lyme disease season beginning 1 month after receiving the booster dose (28 days after completion of the booster dose until 31 October) ]
  Nonvaccine-antigen seroconversion as measured at the central laboratory
• Vaccine efficacy among participants enrolled from North American sites [ Time Frame: In the Lyme disease season beginning 1 month after completing the primary series (28 days after completion of the primary series until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Vaccine efficacy among participants enrolled from European sites [ Time Frame: In the Lyme disease season beginning 1 month after completing the primary series (28 days after completion of the primary series until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Vaccine efficacy among participants enrolled from North American sites [ Time Frame: In the Lyme disease season beginning 1 month after receiving the booster dose (28 days after completion of the booster dose until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee
• Vaccine efficacy among participants enrolled from European sites [ Time Frame: In the Lyme disease season beginning 1 month after receiving the booster dose (28 days after completion of the booster dose until 31 October) ]
  A confirmed case of Lyme disease, caused by B burgdorferi sensu lato, is defined as a clinically suspected case of Lyme disease that is confirmed by PCR, culture, microbial cell-free B burgdorferi-specific DNA sequencing, or serological antiborrelial antibody assay, and finally assessed and confirmed to be a case by the Endpoint Adjudication Committee

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15)
• Official Title: A Phase 3, Multicenter, Placebo-Controlled, Randomized, Observer-Blinded Trial to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, and Lot Consistency of a 6-Valent OspA-Based Lyme Disease Vaccine in Healthy Participants ≥5 Years of Age

Brief Summary

The main purpose of this clinical study is to evaluate a 6-valent OspA-based Lyme disease vaccine (VLA15) for prevention of Lyme disease within North America and Europe. Approximately 9,000 healthy participants 5 years and older will be recruited from areas with high levels of endemic Lyme disease to receive VLA15 or placebo (an inactive substance consisting of saltwater). Each participant will have about a 50% chance of receiving VLA15 and about a 50% chance of receiving placebo. A subset of participants will receive VLA15 from 3 different lots or placebo (1:1:1:3 ratio) to assess lot equivalence.

Participants will receive a 3-dose primary vaccination series at about 0, 2, and 5 to 9 months and then receive a booster dose about 12 months later. Vaccination of participants will occur at a time of year such that the primary series is completed before the peak Lyme disease season followed by a booster dose just prior to the beginning of the second Lyme disease season.

Comparison will be made between the Lyme disease cases of people receiving the study vaccine to those of the people who are not. This will help us determine if the study vaccine is safe and effective.

If enrolled, participants will need to visit the research site at least 7 times during the study. There will also be at least 5 telephone contacts. It is expected that each participant will take part in this study for up to about 2 and a half years.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Lyme Disease

Intervention

• Biological: VLA15
  Shot in the deltoid muscle (preferable in the nondominant arm)
• Other: Saline
  Shot in the deltoid muscle (preferable in the nondominant arm)

Study Arms

• Experimental: VLA15 Lot 1 (3-dose primary vaccination series and booster dose)
  Shot in the deltoid muscle (preferable in the nondominant arm)
  Intervention: Biological: VLA15
• Experimental: VLA15 Lot 2 (3-dose primary vaccination series and booster dose)
  Shot in the deltoid muscle (preferable in the nondominant arm)
  Intervention: Biological: VLA15
• Experimental: VLA15 Lot 3 (3-dose primary vaccination series and booster dose)
  Shot in the deltoid muscle (preferable in the nondominant arm)
  Intervention: Biological: VLA15
• Placebo Comparator: Placebo (3-dose primary vaccination series and booster dose)
  Shot in the deltoid muscle (preferable in the nondominant arm)
  Intervention: Other: Saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 21, 2024): 8318
• Original Estimated Enrollment (submitted: July 25, 2022): 18000
• Estimated Study Completion Date: December 26, 2025
• Estimated Primary Completion Date: December 26, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Participants who reside in areas with endemic Lyme disease and who lead lifestyles that put them at increased risk for Lyme disease. For example, this could include, but not be limited to:
• Individuals who work in B burgdorferi-infected/tick-infested areas, especially those with occupations that may be associated with higher risk of exposure, such as landscaping, forestry, and wildlife and parks management.
• Individuals who pursue recreational activities such as hiking, camping, fishing, hunting, jogging, or gardening in such areas.
• Individuals who live on land plots with tree lines and come into contact with these trees regularly.
• Individuals who have dogs that regularly are outdoors and frequently return with attached ticks.
• Individuals who participate in activities in areas with tall grass, smaller wooded areas beside forests, open fields, lakesides, and riversides.

Key Exclusion Criteria:

• Any female participants that are pregnant (or have a positive urine pregnancy test) or are breastfeeding.
• Any diagnosis of Lyme disease within the past 3 months.
• Any history of Lyme carditis, neuroborreliosis, or arthritis, or other disseminated Lyme disease regardless of when diagnosed.
• Known tick bite within the past 4 weeks.
• Newly developed or unstable underlying conditions that may interfere with the assessment of Lyme disease, including but not limited to chronic arthralgia/arthritis, second/third-degree AV heart block, chronic pain syndromes, and chronic skin conditions that reduce the ability to detect cutaneous manifestations of Lyme disease.
• Any unstable autoimmune condition with a manifestation (eg, arthritic and neurologic) that may interfere with the assessment of Lyme disease.
• Chronic systemic doxycycline or minocycline or other tetracycline class drug use for acne or any other chronic suppressive antibiotics used to treat other conditions.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Finland, Germany, Netherlands, Poland, Sweden, United States

Administrative Information

• NCT Number: NCT05477524
• Other Study ID Numbers: C4601003; 2021-005427-20 ( EudraCT Number ); 2021-005427-20 ( Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Valneva Austria GmbH

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2024