Phase 1/2 Lyme Vaccine Study

Randomized, Double-Blind, Phase 1/2 Clinical Study to Investigate the Safety and Immunogenicity of a Multivalent Recombinant OspA Lyme Borreliosis Vaccine (mv rOspA LB Vaccine) in Healthy Subjects Aged 18 to 70 Years

Section 1:

The purpose of the study is to obtain safety and immunogenicity data of different dose levels of a multivalent recombinant OspA Lyme Borreliosis (mv rOspA LB) Vaccine with and without adjuvant in seronegative healthy adults aged 18 to 70 years. The outcome shall provide the basis for dose/formulation selection for Section 2 of the study.

Section 2:

An additional purpose of the study is to evaluate the safety and immunogenicity of the optimal dose(s)/formulation of the mv rOspA LB Vaccine in a larger population of seronegative and seropositive healthy subjects aged 18 to 70 years.

Study Overview

• Status: Completed
• Conditions: Prophylaxis of Lyme Borreliosis
• Intervention / Treatment: Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine

• Study Type: Interventional
• Enrollment (Actual): 1630
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna, Dept. of Clinical Pharmacology
  • Vienna, Austria, 1090
    • Zentrum für Reisemedizin (Center for Travel Medicine)
• Germany
  • Berlin, Germany, 10117
    • Berliner Centrum für Reise- und Tropenmedizin GmbH (BCRT)
  • Dresden, Germany, 01307
    • GWT-TUD GmbH
  • Freiburg, Germany, 79117
    • Hautarztpraxis Cutanis (Dermatologist)
  • Mainz, Germany, 55116
    • Internistische Gemeinschaftspraxis (Internal Medicine Group Practice)
  • Rodgau, Germany, 63110
    • Innomed Dr. Naudts Klinische Forschung
  • Tübingen, Germany, 72074
    • Universitätsklinikum Tübingen, Abtlg. Tropenmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Subject is 18 to 70 years old at the time of screening
• Subject has an understanding of the study, agrees to its provisions, and gives written informed consent prior to study entry
• Subject is generally healthy, as determined by the investigator's clinical judgment through collection of medical history and the performance of a physical examination
• If female of childbearing potential, presents with a negative urine pregnancy test, and agrees to employ adequate birth control measures for the duration of the study

Additional inclusion criterion for seropositive subjects in Section 2 only:

- Subject is seropositive for Borrelia burgdorferi sensu lato (s.l.) antibodies at study entry

Main Exclusion Criteria:

• Subject has a physician-diagnosed chronic illness related to Lyme borreliosis (LB) or active LB
• Subject has been treated for LB with antibiotics within 3 months of study entry
• Subject had a tick bite within 3 weeks prior to screening or first vaccination
• Subject has a history or active infection with Babesia microti (babesiosis) or Anaplasma phagocytophilum (ehrlichiosis)
• Subject currently has or has a history of significant cardiovascular, respiratory (including asthma), metabolic, neurological, hepatic, rheumatic, autoimmune, hematological, gastrointestinal or renal disorder
• Subject has clinically significant abnormal laboratory values at screening
• Subject currently has or has a history of immunodeficiency
• Subject tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
• Subject has a disease or is currently undergoing a form of treatment or was undergoing a form of treatment within 30 days prior to study entry that could be expected to influence immune response.
• Subject has a history of anaphylaxis or severe allergic reactions
• Subject has received any live vaccine within 4 weeks or inactivated vaccine within 2 weeks prior to vaccination in this study
• Subject is pregnant or lactating at the time of study enrollment

Additional exclusion criterion for subjects in Section 1 and seronegative subjects in Section 2:

- Subject is seropositive for Borrelia burgdorferi sensu lato (s.l.) antibodies at study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary vaccination in seronegative subjects	Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Primary vaccination (6 study arms of 50 subjects each): 3 intramuscular injections containing either dose A, B or C in an adjuvanted or non-adjuvanted formulation (6 different formulations) given in monthly intervals (recruited in 3 sequential cohorts); Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Booster vaccination 9-12 months after first vaccination in Section 1 subjects; Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; 3 intramuscular injections at monthly intervals (using 2 formulations selected from Section 1) in seronegative and seropositive subjects (N=350) and a booster vaccination at 6 months or at 9-12 months (Cohorts 4: seronegatives; Cohort 5: seropositives)
Experimental: Booster vaccination in seronegative subjects	Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Primary vaccination (6 study arms of 50 subjects each): 3 intramuscular injections containing either dose A, B or C in an adjuvanted or non-adjuvanted formulation (6 different formulations) given in monthly intervals (recruited in 3 sequential cohorts); Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Booster vaccination 9-12 months after first vaccination in Section 1 subjects; Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; 3 intramuscular injections at monthly intervals (using 2 formulations selected from Section 1) in seronegative and seropositive subjects (N=350) and a booster vaccination at 6 months or at 9-12 months (Cohorts 4: seronegatives; Cohort 5: seropositives)
Experimental: Primary + booster vacc. (seronegative + seropositive subjects)	Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Primary vaccination (6 study arms of 50 subjects each): 3 intramuscular injections containing either dose A, B or C in an adjuvanted or non-adjuvanted formulation (6 different formulations) given in monthly intervals (recruited in 3 sequential cohorts); Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; Booster vaccination 9-12 months after first vaccination in Section 1 subjects; Biological: Multivalent recombinant OspA Lyme Borreliosis Vaccine; 3 intramuscular injections at monthly intervals (using 2 formulations selected from Section 1) in seronegative and seropositive subjects (N=350) and a booster vaccination at 6 months or at 9-12 months (Cohorts 4: seronegatives; Cohort 5: seropositives)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Antibody response to the vaccine	28 days after the third vaccination (= Day 85)
Frequency and severity of injection site and systemic reactions	Within 7 days after each vaccination (i.e. Days 8, 36 and 64)

Secondary Outcome Measures

Outcome Measure	Time Frame
Antibody response	At baseline, 28 days after each vaccination (i.e. Days 29, 57 and 85), 180 and 270 days after the first vaccination (Day 181, Day 271) and 180 days after the booster vaccination (Day 361 or Day 451 - 546)
Fold increase in antibody titer compared to baseline	28 days after each vaccination, 180 and 270 days after the first vaccination and 180 days after the booster vaccination
Seroconversion rate (at least 4-fold increase of each rOspA type-specific Immunoglobulin G (IgG) titer) as compared to baseline	28 days after each vaccination, 180 and 270 days after the first vaccination and 180 days after the booster vaccination
Frequency and severity of adverse events	28 days after each vaccination and during entire study period

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Baxter Innovations GmbH

Publications and helpful links

General Publications

• Wressnigg N, Barrett PN, Pollabauer EM, O'Rourke M, Portsmouth D, Schwendinger MG, Crowe BA, Livey I, Dvorak T, Schmitt B, Zeitlinger M, Kollaritsch H, Esen M, Kremsner PG, Jelinek T, Aschoff R, Weisser R, Naudts IF, Aichinger G. A Novel multivalent OspA vaccine against Lyme borreliosis is safe and immunogenic in an adult population previously infected with Borrelia burgdorferi sensu lato. Clin Vaccine Immunol. 2014 Nov;21(11):1490-9. doi: 10.1128/CVI.00406-14. Epub 2014 Sep 3.
• Wressnigg N, Pollabauer EM, Aichinger G, Portsmouth D, Low-Baselli A, Fritsch S, Livey I, Crowe BA, Schwendinger M, Bruhl P, Pilz A, Dvorak T, Singer J, Firth C, Luft B, Schmitt B, Zeitlinger M, Muller M, Kollaritsch H, Paulke-Korinek M, Esen M, Kremsner PG, Ehrlich HJ, Barrett PN. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial. Lancet Infect Dis. 2013 Aug;13(8):680-9. doi: 10.1016/S1473-3099(13)70110-5. Epub 2013 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): September 13, 2011
• Study Completion (Actual): February 28, 2014

Study Registration Dates

• First Submitted: December 22, 2011
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (Estimate): January 5, 2012

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Tick-Borne Diseases; Spirochaetales Infections; Lyme Disease; Borrelia Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 730901; 2010-023384-18 (EudraCT Number)