Lyme Disease Description
VLA15 is a multivalent Lyme Disease vaccine candidate that targets the outer surface protein A (OspA) of Borrelia. It is designed for prophylactic, active immunization against Lyme disease aiming for protection against the majority of human pathogenic Borrelia species.
The VLA15 vaccine is currently the only active vaccine program in clinical development against Lyme disease. The program was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in July 2017 and Valneva reported positive interim Phase 1 results in March 2018.
Lyme disease is a systemic infection caused by Borrelia bacteria transmitted to humans by infected Ixodes ticks. It is considered the most common vector-borne illness in the Northern Hemisphere.
The VLA15 Lyme disease vaccine is designed to confer protection by raising antibodies that prevent Borrelia from migrating from ticks to humans after a bite. The safety profile is expected to be similar to other vaccines using the same technology that has been approved for active immunization in adults and children. The medical need for a Lyme disease vaccine is steadily increasing as the disease footprint continues to widens in the USA and in Europe.
The target population includes individuals at risk above 2 years of age living in endemic areas, people planning to travel to endemic areas to pursue outdoor activities and people at risk who have a history of Lyme disease (an infection with Borrelia does not confer protective immunity against all pathogenic Borrelia species).
VLA15 is administered as intramuscular injections on Day 1, Day 57 and Day 180.
VLA15-201 is a randomized, observer-blind, placebo-controlled trial conducted at trial sites in the U.S. and Europe. VLA15 is tested as an alum adjuvanted formulation and administered intramuscularly in three injections, given one month apart at Days 1, 29 and 57. Subjects will be followed for one year, with the main immunogenicity readout one month after the third immunization on Day 85 (primary endpoint).
VLA15-202 is the 2nd of two planned Phase 2 studies. It is a randomized, observer-blind, placebo-controlled trial conducted at trial sites in the US. 246 subjects will receive one of two dosage levels of VLA15 or placebo. Subjects will be followed for 18 months, with the main immunogenicity readout on Day 208 (primary endpoint).
September 30, 2019: Valneva SE announced that it has completed patient recruitment of the Phase 2 studies for its Lyme disease vaccine candidate, VLA15. Valneva SE said in a press release published on September 30, 2019, comprising immunogenicity and safety data from these studies are expected in mid-2020, will support the dose and vaccination schedule to be used in Phase 3 clinical studies.
July 1, 2019: A second Phase 2 clinical trial for the development of Lyme disease vaccine candidate VLA15 has been announced. Following the Run-In phase for Valneva’s first Phase 2 study VLA15-201, the two dosage levels (135µg and 180µg) have been selected for further development based on Data and Safety Monitoring Board clearance.
June 12, 2019: An independent Data Safety Monitoring Board (DSMB) has cleared two dosage levels to be used for clinical development.
First quarter of 2019: Valneva reported final Phase 1 data and initial booster data.
- Overall, the final data confirmed conclusions from the interim data, and the booster evaluations showed a very significant increase in immunogenicity.
- As circulating antibody levels are important for OspA-based vaccines, higher dosages are being tested in Phase 2, aiming to induce an earlier, higher and more durable immune response.
Clinical Trial NCT03970733: Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis (Active)
- The objectives for this Phase 2 VLA15-202 clinical study are to determine the optimal dosage level and vaccination schedule for use in Phase 3 pivotal field efficacy studies, based on immunogenicity and safety data.
- A total of 250 subjects will be randomized 2:2:1 into three treatment groups to receive either VLA15 with Alum (two different dose levels) or Placebo.
- The study duration per subject will be a maximum of 19 months. Overall study Duration is estimated to be 21 months.
Clinical Trial NCT03769194: A Phase 2 Randomized, Controlled, Observer-blind Study to determine the Immunogenicity and Safety of a Vaccine Against Lyme Borreliosis, in Healthy Adults Aged 18 to 65 Years. (Active)
- This ongoing Phase 2 study (VLA15-201) involves 120 subjects and testing of three dosage levels of VLA15, or placebo.
- Enrolment of subjects for the run-in phase has been completed.
- Based upon a final review of the run-in safety data by a Data Safety Monitoring Board (DSMB), the two highest safe doses will be taken further into the main study phase.
Clinical Trial NCT03010228: A Phase 1 Study Assessing the Safety, Immunogenicity, and Dose-Response of VLA15, A New Vaccine Candidate Against Lyme Borreliosis (Completed)
This is an observer-blind, partially randomized, multi-center dose-escalation Phase I study which aims to assess the safety, immunogenicity, and dose-response of VLA15 in healthy adults aged below 40 years.
- Overall 180 subjects will be enrolled in 6 treatment groups: VLA15 12µg with and w/o (without) Alum, VLA15 48µg with and w/o Alum, VLA15 90µg with and w/o Alum.
- For the first 24 subjects, the study will be open-label and subjects will not be randomized but included in a staggered dose escalation scheme for safety precaution. Thereafter, the study will be conducted observer-blind in respect to the investigators and site staff involved in clinical evaluation of subjects, subjects will be blinded as well.
- The remaining 156 subjects will be randomized into the 6 treatment groups. I.M. vaccinations are administered on Days 0, 28 and 56 into the deltoid region of the non-dominant arm.
- The study will investigate the safety and tolerability as well as the immunogenicity of VLA15.
- The primary objective addresses the safety and tolerability of the vaccine up to three months after enrollment, i.e. 84 days after the first vaccination. The study includes 1 screening visit and 8 outpatient visits from day 0 through day 365. In addition, safety phone calls will be performed.
- Subjects in the 48µg and 90µg dose Groups at the Belgian site, who received a complete primary immunization schedule (three vaccinations), will be included in a Booster Extension to investigate the safety and immunogenicity of a booster dose of VLA15 administered 13 months after the first immunization.
- An extension analysis on safety and immunogenicity will be performed after the last subject has completed the last study visit at Month 19.
- Additionally, an M14 interim analysis on immunogenicity data will be performed, when all subjects completed Month 14.
- For inclusion in the Booster Extension of this study only subjects are eligible, who were enrolled in Belgium, completed the primary immunization schedule (three vaccinations) and were randomized into 48µg or 90µg dose groups with or without alum. Subjects included in the staggered dose-escalation phase will not be asked to participate in the Booster Extension for operational reasons.
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