Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis
Condition: Lyme Borreliosis
MeSH terms: Borrelia Infections; Lyme Disease
Intervention: VLA15; Placebo
Intervention description: a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate; PBS (Phosphate Buffered Saline)
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 246.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: VLA15; Lyme Borreliosis; Vaccine

Summary:

      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.
    

Eligibility criteria:

        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).