| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Prevention of Lyme disease caused by Borrelia species in individuals ≥5 years of age by active immunization | |
| E.1.1.1 | Medical condition in easily understood language | | Prevention of Lyme disease | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10025169 | | E.1.2 | Term | Lyme disease | | E.1.2 | System Organ Class | 10021881 - Infections and infestations | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Primary Efficacy
1. To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in the Lyme disease season after completion of the primary series vaccination and booster dose.
Primary Safety
1.To describe the safety profile of VLA15 as measured by the percentage of participants reporting local reactions, systemic events, AEs, NDCMCs, and SAEs.
Primary Immunogenicity
1.To demonstrate that the immune responses to the 6 serotypes induced by VLA15 are equivalent across 3 independent lots.
2.To demonstrate that the immune responses to the 6 serotypes induced by VLA15 in children 5 through 17 years of age are noninferior to those in adults 18 through 44 years of age after the booster dose. | |
| E.2.2 | Secondary objectives of the trial | Secondary Efficacy
1. To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in the Lyme disease season after completion of the primary series vaccination and booster dose in NA.
2. To demonstrate the efficacy of VLA15 in preventing confirmed Lyme disease in the Lyme disease season after completion of the primary series vaccination. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1.Male or female participants ≥5 years of age at enrollment (signing of ICD or assent) in all countries where pediatric enrollment is permitted. In countries or sites where enrollment of children is not permitted, male or female participants ≥18 years of age at the time of informed consent.
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2.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.
•Any other risk factors determined at the discretion of the investigators.
3.Participants or participants' parent(s)/legal guardian(s), as age appropriate, who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures; are expected to be available for the duration of the study; and can be contacted by telephone during study participation.
4.Healthy male and female participants at enrollment who are determined by medical history and clinical judgment of the investigator to be eligible for inclusion in the study. Participants with preexisting chronic medical conditions determined to be stable may be included.
Informed Consent and Assent (as Appropriate):
5.Capable of giving signed informed consent, and assent (as appropriate), as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. The investigator, or a person designated by the investigator, will obtain informed consent (and assent, as appropriate) from each study participant or study participant's parent(s)/legal guardian (as defined in Appendix 1) before any study-specific activity is performed. All parent(s)/legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand. The investigator will retain the original copy of each participant's signed consent (and assent, as appropriate) document(s). | |
| E.4 | Principal exclusion criteria | Participants are excluded from the study if any of the following criteria apply:
1.Pregnant female participants; breastfeeding female participants; positive urine pregnancy test for female participants at Visit 1 (prior to vaccination); WOCBP who are, in the opinion of the investigator, sexually active and at risk for pregnancy; and fertile men and WOCBP who are unwilling or unable to use effective methods of contraception as outlined in this protocol from the signing of the informed consent through 28 days after completion of the primary vaccination series and from the booster dose through 28 days after the booster vaccination.
Medical Conditions:
2.Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.
3.Any diagnosis of Lyme disease within the past 3 months.
4. Any history of Lyme carditis, neuroborreliosis, arthritis, or other disseminated Lyme disease regardless of when diagnosed.
5.Known tick bite within the past 4 weeks.
6.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.
7.Underlying clotting deficiency (eg, bleeding disorder, thrombocytopenia) that may increase the risk of excessive bleeding following required study procedures.
8.Congenital or acquired immunodeficiency or treatments that would inhibit the ability to mount an immune response to a vaccine.
9.Any unstable autoimmune condition with a manifestation (eg, arthritic and neurologic) that may interfere with the assessment of Lyme disease (Potential participants with well-controlled, stable autoimmune conditions under the care of a rheumatologist are eligible).
10.Underlying bone marrow disorder such as myelodysplasia, myeloma, or myeloproliferative disorder, treated within the past year, or any history of bone marrow transplant.
11.Malignancy that required treatment with chemotherapy (including the use of adjunctive and hormonal therapy), immunotherapy, radiation therapy, or antineoplastic target therapies within the past 24 months.
12.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Prior/Concomitant Therapy:
13.Receipt of a previous vaccination for Lyme disease. Note: This includes Lyme vaccine clinical trials where study intervention was received or is unknown.
14.Treatment for Lyme disease in the 3 months prior to study intervention administration.
15.Chronic systemic doxycycline or minocycline or other tetracycline class drug use for acne or any other chronic suppressive antibiotics used to treat other conditions.
16.Receipt of blood/plasma products or immunoglobulins within 6 months before study intervention administration through conclusion of the study.
17.Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for ≥14 days within 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
18.Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months before study intervention administration.
19. Receipt of anticoagulant therapy within 1 month before study intervention administration. Monotherapy with aspirin or standard-dose antiplatelet medications (eg, clopidogrel, ticagrelor, prasugrel, dipyridamole, ticlopidine, eptifibatide) is permitted.
Prior/Concurrent Clinical Study Experience:
20.Participation in other studies involving investigational drug(s), investigational vaccines, or investigational devices within 28 days prior to study entry and/or during study participation. Participation in purely observational studies is acceptable.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
21.Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Primary Efficacy
1. Clinically- and laboratory confirmed Lyme disease caused by B burgdorferi sensu lato (as determined by the EAC).
Primary Safety
1.
• Local reactions (pain at the injection site, redness, and swelling).
• Systemic events (fever, headache, fatigue, muscle pain, and joint pain).
•AEs.
•NDCMCs.
•SAEs.
Primary Immunogenicity
1. Anti-OspA quantitative immunological assay titer.
2. Anti-OspA quantitative immunological assay titer. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | Timepoints described in detail in the Protocol | |
| E.5.2 | Secondary end point(s) | Secondary Efficacy
1. Clinically- and laboratory-confirmed Lyme disease caused by B burgdorferi sensu lato (as determined by the EAC).
2. Clinically- and laboratory-confirmed Lyme disease caused by B burgdorferi sensu lato (as determined by the EAC). | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | Timepoints described in detail in the Protocol | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | | Immunogenicity, Tolerability | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Canada | | United States | | Finland | | Germany | | Netherlands | | Poland | | Sweden | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | Last visit of the last subject | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 26 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
