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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lyme Disease

Intervention / Treatment
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* Biological: VLA15
* Other: Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VLA15 Lot 1 (3-dose primary vaccination series and booster dose)<br>Shot in the deltoid muscle (preferable in the nondominant arm) | Biological: VLA15<br>* Shot in the deltoid muscle (preferable in the nondominant arm)<br>|
| Experimental: VLA15 Lot 2 (3-dose primary vaccination series and booster dose)<br>Shot in the deltoid muscle (preferable in the nondominant arm) | Biological: VLA15<br>* Shot in the deltoid muscle (preferable in the nondominant arm)<br>|
| Experimental: VLA15 Lot 3 (3-dose primary vaccination series and booster dose)<br>Shot in the deltoid muscle (preferable in the nondominant arm) | Biological: VLA15<br>* Shot in the deltoid muscle (preferable in the nondominant arm)<br>|
| Placebo Comparator: Placebo (3-dose primary vaccination series and booster dose)<br>Shot in the deltoid muscle (preferable in the nondominant arm) | Other: Saline<br>* Shot in the deltoid muscle (preferable in the nondominant arm)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative risk reduction of confirmed Lyme disease cases in the VLA15 group compared to the placebo group | 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 | 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)). | 
| Percentage of participants reporting local reactions |  | Within 7 days following each study intervention administration | 
| Percentage of participants reporting systemic events |  | Within 7 days following each study intervention administration | 
| Percentage of participants reporting adverse events (AEs) |  | Through 1 month following each study intervention administration | 
| Percentage of participants reporting newly diagnosed chronic medical conditions (NDCMCs) |  | Through study completion, up to approximately 30 months. | 
| Percentage of participants reporting serious adverse events (SAEs) |  | 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 |  | 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 |  | 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 |  | 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) | Immunobridging objective to determine non-inferiority between 5-17 year old and 18-44 year old participant strata. | At 1 month after completion of the booster dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine efficacy among participants enrolled from North American sites | 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 | 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) | 
| Vaccine efficacy among participants after primary series | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLA15, Lyme Borreliosis, Vaccine, Tick