Phase 2 Study Of VLA15, A Vaccine Candidate Against Lyme Borreliosis, In A Healthy Pediatric And Adult Study Population

Study Overview
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Brief Summary
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VLA15-221 is a Phase 2 study, which will be conducted in two parts: Main Study Phase (Part A) and Booster Phase (Part B). The study will compare the safety and immunogenicity of two different primary immunization schedules applying three (Month 0-2-6) or two (Month 0-6) vaccinations. Within the study, 600 healthy subjects aged 5-65 years will be included. Subjects with a history of Lyme borreliosis (previous infection with Borrelia) as well as Borrelia naïve subjects will be enrolled. Study duration per subject will be a maximum of 19 months in Part A and additional 37 months for subjects enrolled in the Part B.

Detailed Description
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VLA15-221 is a randomized, observer-blind, placebo controlled, multicenter Phase 2 study, which is set up in two parts: Main Study Phase (Part A) and Booster Phase (Part B). In Part A 600 subjects aged 5-65 years will be enrolled 1:1:1 into three groups: Group 1 will be vaccinated with VLA15 at Month 0-2-6, Group 2 will be vaccinated with VLA15 at Month 0-6 and with placebo at Month 2 and Group 3 will be vaccinated with placebo at Month 0-2-6. In Part B all eligible subjects will receive a booster injection with VLA15 or placebo at Month 18.

Official Title
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SAFETY AND IMMUNOGENICITY STUDY OF VLA15, A MULTIVALENT RECOMBINANT OSPA BASED VACCINE CANDIDATE AGAINST LYME BORRELIOSIS: A RANDOMIZED, CONTROLLED, OBSERVER-BLIND PHASE 2 STUDY IN A HEALTHY PEDIATRIC AND ADULT STUDY POPULATION

Conditions
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Lyme Borreliosis

Intervention / Treatment
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* Biological: VLA15
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is aged 5 to 65 years at the day of screening (Visit 0) Subject is of good general health Parent(s)/legal representative(s) and subject understand the study and its procedures, agree to its provisions for subjects aged 18-65 years: written informed consent prior to any study related procedures for subjects aged 5-17 years: written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable, prior to any study related procedures. If subject is of childbearing potential: Subject has a negative serum pregnancy test at screening (Visit 0) and agrees to employ adequate birth control measures according to following timelines: Main Study Phase: duration of entire study Booster Phase: until Month 23 (i.e. 5 months after booster dose) Subject is willing and able to comply with scheduled visits, treatment plan, and other study procedures Subject is available for the duration of the study and can be contacted by telephone during study participation Exclusion Criteria: Subject has a chronic illness related to Lyme borreliosis (LB), an active symptomatic LB, or received treatment for LB within the last 3 months prior to Day 1; Subject received previous vaccination against LB; Subject had a tick bite within 4 weeks prior to Day 1; Subject has a medical history of or currently has a clinically relevant disease; Subject has a medical history of or currently has a neuro-inflammatory or autoimmune disease; Subject has a known thrombocytopenia, bleeding disorder, or received anticoagulants in the 3 weeks prior to Day 1; Subject has received an active or passive immunization within 4 weeks prior to Day 1; Subject has received any other registered or non-registered medicinal product in another clinical trial within 4 weeks prior to vaccination at Day 1; Subject has a known or suspected defect of the immune system or received immuno-suppressive therapy within 4 weeks prior to Day 1; Subject has a history of anaphylaxis of unknown cause or severe allergic reactions of unknown cause or has a known hypersensitivity or allergic reactions to one of the components of the vaccine; Subject had any malignancy in the past 5 years; Subject is pregnant, has plans to become pregnant during the course of the study or is lactating at the time of enrollment; Subject has donated or plans to donate blood or blood-derived products 4 weeks prior to Day 1; Subject has any condition that may compromise its well-being, might interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study; Subject is in a dependent relationship;

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A+B - Group 1<br>Part A: VLA15 at Month 0, 2 and 6 Part B: VLA15 | Biological: VLA15<br>* a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate<br>|
| Experimental: Part A+B - Group 2<br>Part A: VLA15 at Month 0 and 6, placebo at Month 2 Part B: VLA15 | Biological: VLA15<br>* a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate<br>Biological: Placebo<br>* PBS (Phosphate Buffered Saline)<br>|
| Placebo Comparator: Part A+B - Group 3<br>Part A: Placebo at Month 0, 2 and 6 Part B: Placebo | Biological: Placebo<br>* PBS (Phosphate Buffered Saline)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Local and Solicited Systemic Adverse Events (AEs) Within 7 Days After Vaccination 1 | Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 to Day 7 after vaccination 1 at Month 0 | 
| Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 2 | Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 to Day 7 after vaccination 2 at Month 2 | 
| Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 3 | Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 to Day 7 after vaccination 3 at Month 6 | 
| Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Any Vaccination During the Main Study Phase | Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 to Day 7 after vaccination 1, 2 or 3 at Month 0, 2 and 6 respectively | 
| Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) Against Each Outer Surface Protein A (OspA) Serotype (ST1 to ST6) at Day 208 During the Main Study Phase | GMTs for IgG against each OspA serotype ST1 to ST6, determined by an IgG binding assay at Day 208 is presented in this outcome measure. | Day 208 (Month 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Booster Dose | Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. | Within 7 days after booster dose | 
| Percentage of Participants With Serious Adverse Events (SAEs) | SAE was any untoward medical occurrence that at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was another medically important condition. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 of vaccination up to Day 208 (Month 7) | 
| Percentage of Participants With Adverse Events of Special Interest (AESIs) | An AESI (serious or non-serious) was one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor were appropriate. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 of vaccination up to Day 208 (Month 7) | 
| Percentage of Participants With Unsolicited Adverse Events | An AE was any untoward medical occurrence in a participant administered an investigational product, whether or not related to this treatment. Unsolicited AEs were defined as any solicited local or systemic AE if it had an onset date more than 6 days after vaccination or any other symptom or untoward medical event. Two-sided 95% confidence intervals were calculated according to Altman method. | From Day 1 to Day 28 after vaccination 1, 2 and 3 at Month 0, 2 and 6, respectively | 
| Percentage of Participants With SAEs, AESIs, Solicited and Unsolicited AEs Stratified by Age Group | Percentage of participants with SAEs, AESIs, solicited and unsolicited AEs stratified by age group 18 to 65, 12 to 17 and 5 to 11 years were reported. SAE: any untoward medical occurrence that at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was another medically important condition. AESI: scientific and medical concern specific to the sponsor's product or program. Solicited AE: predefined reactions at injection site or systemic reactions after each vaccination. Unsolicited AEs: any solicited local or systemic AE if it had an onset date more than 6 days after vaccination or any other symptom or untoward medical event. Unsolicited AEs were collected only up to 28 days after any vaccination. Two-sided 95% confidence intervals were calculated according to Altman method. | SAEs, AESIs: From Day 1 of vaccination (vac) up to Day 208 (Month 7), Solicited AEs: From Day 1 to Day 7 after vac 1, 2 and 3 at Month 0, 2 and 6, respectively; Unsolicited AEs: From Day 1 to Day 28 after vac 1, 2 and 3 at Month 0, 2 and 6, respectively | 
| GMTs for IgG Against Each OspA Serotype (ST1 to ST6) at Baseline, Day 85, Day 180 and Day 194 During the Main Study Phase | GMTs for IgG against each OspA serotype ST1 to ST6, determined by an IgG binding assay. | Baseline, Day 85, Day 180 and Day 194 | 
| Seroconversion Rate for Each OspA Serotype (ST1 to ST6) Specific IgG at Day 85, 180, 194 and 208 | Seroconversion Rate (SCR) for each OspA serotype specific IgG ST1 to ST6, determined by enzyme linked immunosorbent assay (ELISA). Seroconversion for ELISA was defined as: 1) For participants who were seronegative at screening: percentage of participants with a change from seronegative at screening to seropositive (i.e. antibody titer of >=40 Units per milliliter [U/mL]) at a certain time point. 2) For participants who were seropositive at screening: percentage of participants with a >= 4-fold rise in OspA IgG antibody titer from screening. | Day 85, Day 180, Day 194 and Day 208 | 
| Geometric Mean of the Fold Rise (GMFR) for IgG Against Each OspA Serotype (ST1 to ST6) at Day 85 and Day 208 During the Main Study Phase | GMFR as compared to baseline for IgG against each OspA serotype ST1 to ST6, determined by IgG binding assay at Day 85 and Day 208. | Baseline, Day 85 and 208 | 
| GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Baseline, Day 85, Day 180, Day 194 and Day 208 During the Main Study Phase | GMTs for IgG against each OspA serotype ST1 to ST6, determined by an IgG binding assay stratified by age group (18 to 65, 12 to 17 and 5 to 11 years). | Baseline, Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208 | 
| Seroconversion Rate for Each OspA Serotype (ST1 to ST6) Specific IgG at Day 85, 180, 194 and 208 Stratified by Age Group During the Main Study Phase | SCR for each OspA serotype specific IgG ST1 to ST6, determined by ELISA stratified by age group (18 to 65, 12 to 17 and 5 to 11 years). Seroconversion for ELISA was defined as: 1) For participants who were seronegative at screening: percentage of participants with a change from seronegative at screening to seropositive (i.e. antibody titer of >=40 Units per milliliter [U/mL]) at a certain time point. 2) For participants who were seropositive at screening: percentage of participants with a >= 4-fold rise in OspA IgG antibody titer from screening. | Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208 | 
| Geometric Mean of the Fold Rise (GMFR) for IgG Against Each OspA Serotype (ST1 to ST6) at Day 85, Day 180, Day 194 and Day 208 Stratified by Age Group During the Main Study Phase | GMFR as compared to baseline for IgG against each OspA serotype ST1 to ST6, stratified by age group (18 to 65, 12 to 17 and 5 to 11 years) determined by IgG binding assay at Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208. | Baseline, Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208 | 
| GMTs for IgG Against Each OspA Serotype (ST1 to ST6) During the Booster Phase |  | Up to Month 54 | 
| SCR for Each OspA Serotype (ST1 to ST6) IgG During the Booster Phase | Seroconversion for ELISA was defined as: 1) For participants who were seronegative at screening: a change from seronegative at screening to seropositive (i.e. antibody titer of >=40 U/mL) at a certain time point. 2) For participants who were seropositive at screening: a >= 4-fold rise in OspA IgG antibody titer from screening. | Up to Month 54 | 
| GMFR for IgG Against Each OspA Serotype (ST1 to ST6) at Month 19 During the Booster Phase |  | Month 19 | 
| GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Cohort During the Booster Phase |  | Up to Month 54 | 
| SCR for Each OspA Serotype (ST1 to ST6) IgG Stratified by Age Cohort During the Booster Phase | Seroconversion for ELISA was defined as: 1) For participants who were seronegative at screening: a change from seronegative at screening to seropositive (i.e. antibody titer of >=40 U/mL) at a certain time point. 2) For participants who were seropositive at screening: a >= 4-fold rise in OspA IgG antibody titer from screening. | Up to Month 54 | 
| GMFR for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Cohort During the Booster Phase |  | Up to Month 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLA15, Lyme Borreliosis, Vaccine, Lyme disease, Borrelia