Immunogenicity and Safety Study of a Vaccine Against Lyme Borreliosis, in Healthy Adults Aged 18 to 65 Years. Randomized, Controlled, Observer-blind Phase 2 Study.

This is a randomized, observer-blind, placebo controlled, multicenter Phase 2 study conducted in two study phases: a run-in phase and a main study phase. The study was investigated 3 doses of a multivalent OspA (Outer Surface Protein A) based Lyme vaccine (VLA15) in healthy adults aged 18 to 65 years of age. Study participants received 3 immunizations of the vaccine at a monthly interval. The study assessed the immune response as well as the safety profile of the vaccine.

This is a randomized, observer-blind, placebo controlled, multicenter Phase 2 study.

In the Run-in phase, a total of 120 subjects aged 18 to 40 years were randomized 1:1:1:1 to receive one of three VLA15 doses (VLA15 low dose (90 µg), VLA15 medium dose (135 µg), VLA15 high dose (180 µg)) or Placebo as intramuscular vaccinations on Days 1, 29 and 57.

Dosing was adjusted by injection volume.

In the Main Study phase, a total of 452 subjects aged 18 to 65 years were randomized 2:2:1 to receive VLA15 135 µg or VLA15 180 µg, the two dose groups were selected from the Run-in-Phase or placebo, as intramuscular vaccinations on Days 1, 29 and 57. Subjects were enrolled in two age groups (18-49 years and 50-65 years) in a ratio of approx. 2:1.

In both study phases, target was to enroll approx. 10 % or more of subjects that were baseline seropositive for Borrelia burgdorferi sensu latu (Bb s.l.).

Eligibility Criteria:
Inclusion Criteria:

Run-in phase:

1. Subject is aged 18 to 40 years at the day of screening (Visit 0);

Main Study phase:

1. Subject is aged18 to 65 years at the day of screening (Visit 0);

   Run-in phase and Main Study phase:
2. Subject is of good general health, including subjects with pharmacologically controlled chronic conditions;
3. Subject has an understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to any study-related procedures;
4. If subject is of childbearing potential:

   1. Subject has a negative serum pregnancy test at screening (Visit 0);
   2. Subject agrees to employ adequate birth control measures for the duration of the study.

Exclusion Criteria:

1. Subject has a chronic illness related to Lyme borreliosis (LB), an active symptomatic LB (Lyme borreliosis) as suspected or diagnosed by a physician, or received treatment for LB (Lyme borreliosis) within the last 3 months prior to Visit 0;
2. Subject received previous vaccination against Lyme borreliosis (LB).;
3. Subject had a tick bite within 4 weeks prior to Visit 1;
4. Subject has a medical history of or currently has a clinically relevant disease (cardiovascular, respiratory, neurologic, psychiatric conditions) which poses a risk for participation in the study, based on investigators judgement, such as individuals with poorly controlled or unstable disease, ongoing suspected or active inflammation, or poor compliance with pharmacologic treatment. Subjects with pharmacologically controlled conditions like osteoarthritis, depression, or asthma are eligible;
5. Subject has a medical history of or currently has a neuroinflammatory or autoimmune disease, including Guillain Barré Syndrome;
6. Subject has a known thrombocytopenia, bleeding disorder, or received anticoagulants in the 3 weeks prior to first vaccination or until Day 57 (Visit 3), contraindicating intramuscular vaccination as judged by the investigator;
7. Subject has received an active or passive immunization within 28 days before first vaccination at Visit 1 and until Day 85; except for influenza (seasonal or pandemic) and pneumococcal vaccines which may be administered outside a 7-days interval before or after any trial vaccination;
8. Subject has received any other non-registered medicinal product in another clinical trial within 28 days prior to VLA15 vaccination at Visit 1 (Day 1) and throughout the entire study period or has received a registered medicinal product in another clinical trial within 28 days prior to VLA15 vaccination at Visit 1 (Day 1) and up to Day 85;
9. Subject has a known or suspected defect of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired immunodeficiency, including infection with human immunodeficiency virus (HIV), status post organ transplantation or immuno-suppressive therapy within 30 days prior to Visit 1. Immuno-suppressive therapy is defined as administration of chronic (longer than 14 days) prednisone or equivalent 0.05 mg per kg/ per day. Topical and inhaled steroids are allowed;
10. Subject has a history of anaphylaxis or severe allergic reactions or a known hypersensitivity or allergic reactions to one of the components of the vaccine;
11. Subject had any malignancy in the past 5 years. If treatment for cancer was successfully completed more than 5 years ago and the malignancy is considered to be cured, the subject may be enrolled;
12. Subject had acute febrile infections within 10 days prior to first vaccination;
13. Subject is pregnant (positive serum pregnancy test at screening), has plans to become pregnant during the course of the study or is lactating at the time of enrollment. Women of childbearing potential that are unwilling or unable to employ an adequate birth control measure for the duration of the study.
14. Subject has donated blood or blood-derived products (plasma) within 30 days or received blood or blood-derived products (plasma) within 90 days prior to first vaccination in this study or plans to donate or use blood or blood products during the course of the study;
15. Subject has any condition that, in the opinion of the investigator, may compromise the subject's well-being, might interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;
16. Subject is committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities);
17. Subject is in a dependent relationship with the sponsor, an investigator or other study team member, or the study center. Dependent relationships include close relatives and household members (i.e. children, partner/spouse, siblings, parents) as well as employees of the investigator or study center personnel.