Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis

ALTERNATIVE SCHEDULE STUDY FOR VLA15, A MULTIVALENT RECOMBINANT OSPA BASED VACCINE CANDIDATE AGAINST LYME BORRELIOSIS, IN HEALTHY ADULTS AGED 18 TO 65 YEARS - A RANDOMIZED, CONTROLLED, OBSERVER-BLIND PHASE 2 STUDY.

In the Main Study Phase a total of 246 subjects were randomized 2:2:1 into three treatment groups to receive either VLA15 with Alum (lower or higher dose) or Placebo. Main Study Phase vaccinations were administered as intramuscular injections on Day 1, Day 57 and Day 180.

In the Booster Phase subjects from the higher dose group who completed their primary immunization schedule according to protocol will be randomized 2:1 to receive an additional higher dose VLA15 vaccination or Placebo at Month 18.

Study duration in the Main Study Phase per subject is a maximum of 20 months. Overall study Duration is estimated to be 22 months.

Study duration per subject in the Booster Phase is a maximum of approximately 13 months.

Study duration per subject in the Main Study Phase and Booster Phase together is estimated to be a maximum of approximately 33 months.

Overall study duration (i.e., First-Subject-In to Last-Subject Out/ end of Booster Phase) is estimated to be approximately 37 months.

This is a randomized, observer-blind (subject, Sponsor and investigator/site staff involved in Clinical Evaluation of subjects are blinded), Placebo controlled, multicenter Phase 2 study.

In Main Study Phase a total of 246 healthy subjects,aged 18 to 65 years, were randomized 2:2:1 to receive either VLA15 with Alum (lower or higher doser Placebo. Main Study Phase vaccinations were administered as intramuscular injections on Day 1 (Month 0), Day 57 (Month 2) and Day 180 (Month 6).

Subjects from the higher dose group who completed their primary immunization schedule according to protocol, will be randomized 2:1 to receive an additional injection of the higher dose VLA15 with Alum or Placebo in a Booster Phase. The additional vaccination is administered as intramuscular injection approximately 18 months after the first immunization.

Inclusion Criteria - Main Study Phase:

• Subject is aged 18 to 65 years at the day of screening
• Subject is of good general health, including subjects with pharmacologically controlled chronic conditions;
• 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;
• If subject is of childbearing potential:
• Subject has a negative serum pregnancy test at screening;
• Subject agrees to employ adequate birth control measures for the duration of the study.

Inclusion Criteria - Booster Phase:

1. Randomization into higher dose group in the Main Study Phase

2. No relevant protocol deviation in the Main Study Phase, i.e., included in the Per-Protocol population for the Day 208 interim analysis of the Main Study;

3. Subject is of good general health, including subjects with pharmacologically controlled chronic conditions;

4. 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;

5. If subject is of childbearing potential:

   1. Subject has a negative Urine pregnancy test before booster vaccination;
   2. Subject agrees to employ adequate birth control measures for the duration of the study

Exclusion Criteria - Main Study Phase:

• Subject has a chronic illness related to Lyme borreliosis (LB), an active symptomatic LB as suspected or diagnosed by a physician, or received treatment for LB within the last 3 months prior to screening;
• Subject received previous vaccination against LB.;
• Subject had a tick bite within 4 weeks prior to vaccination visit;
• Subject has a medical history of or currently has a clinically relevant disease (e.g. 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;
• Subject has a medical history of or currently has a neuroinflammatory or autoimmune disease, including Guillain Barré Syndrome;
• Subject has a known thrombocytopenia, bleeding disorder, or received anticoagulants in the three weeks prior to each study vaccination, contraindicating I.M. vaccination as judged by the investigator;
• Subject has received an active or passive immunization within 28 days before or after any vaccination; except for influenza (seasonal or pandemic) vaccines which may be administered outside a 7-days interval before or after any trial vaccination;
• Subject has received any other non-registered medicinal product in another clinical Trial within 28 days prior to VLA15 vaccination and throughout the entire study period or has received a registered medicinal product in another clinical Trial within 28 days prior to VLA15 vaccination and up to Day 208;
• 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 first vaccination. Immuno-suppressive therapy is defined as administration of chronic (longer than 14 days) prednisone or equivalent >=0.05 mg/kg/day. Topical and inhaled steroids are allowed;
• 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; 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;
• Subject had acute febrile infections within 10 days prior to first vaccination;
• 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.
• Subject has donated blood or blood-derived products (e.g. plasma) within 30 days or received blood or blood-derived products (e.g. 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;
• 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;
• Subject is committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities);
• 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.

Exclusion Criteria - Booster Phase:

1. Subject met an individual stopping criterion during the Main Study Phase;
2. Subject has developed a chronic illness related to Lyme borreliosis (LB), an active symptomatic LB as suspected or diagnosed by a physician, or received treatment for LB within the last 3 months prior to vaccination visit;
3. Subject has developed a clinically relevant disease (e.g. cardiovascular, respiratory, neurologic, psychiatric conditions) which poses a risk for further 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;
4. Subject has developed a neuroinflammatory or autoimmune disease, including Guillain Barré Syndrome;
5. Subject has developed an immunodeficiency, including known infection with human immunodeficiency virus (HIV), status post organ transplantation, or immuno-suppressive therapy within 30 days prior to vaccination visit. Immuno-suppressive therapy is defined as administration of chronic (longer than 14 days) prednisone or equivalent >= 0.05 mg/kg/day. Topical and inhaled steroids are allowed;
6. Subject has developed anaphylaxis or severe allergic reactions;
7. Subject has developed allergic reactions to one of the components of the vaccine;
8. Subject has developed a malignancy;
9. Subject has developed thrombocytopenia or received anticoagulants in the 3 weeks prior to the booster vaccination contraindicating I.M. vaccination as judged by the investigator;
10. Subject has received any other non-registered medicinal product in another clinical trial within 28 days prior to VLA15 booster vaccination at Month 18 or plans to participate in another clinical trial with a non-registered medicinal product until Month 24;
11. Subject is pregnant, or plans to become pregnant prior to Month 24, or is lactating. Women of childbearing potential that are unwilling or unable to employ an adequate birth control measure for the duration of the study;
12. Subject has developed 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;
13. Subject has been committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities);
14. 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, sibling).