Alternative Schedule Study For VLA15, a Vaccine Candidate... | NCT03970733

NCT03970733

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
C4601007	Other Identifier	Alias Study Number

Status Module

Sponsor/Collaborators Module

Name	Class
Valneva Austria GmbH	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
VLA15 with Alum lower dose	Experimental	Main Study Phase: VLA15 with Alum lower dose - Booster Phase: arm discontinued	Biological: VLA15
VLA15 with Alum higher dose	Experimental	Main Study Phase: VLA15 with Alum higher dose - Booster Phase: VLA15 higher dose or placebo	Biological: VLA15
Placebo	Placebo Comparator	Main Study Phase: placebo - Booster Phase: arm discontinued	Biological: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
VLA15	Biological	a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate	VLA15 with Alum higher dose VLA15 with Alum lower dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
GMTs for IgG Against Each OspA Serotype	Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) against each Outer Surface Protein A (OspA) serotype ST1 to ST6, determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 208 (Month 7)	Day 208 (Month 7)

Secondary Outcomes

Measure	Description	Time Frame
GMTs for IgG Against Each OspA Serotype During the Main Study Phase	GMTs for IgG against each OspA serotype ST1 to ST6, determined by ELISA, at Day 1 (Month 0), 29 (Month 1), 57 (Month 2), 85 (Month 3), 180 (Month 6), 365 (Month 12) and 545 (Month 18).	At Day 1 (Month 0), Day 29 (Month 1), Day 57 (Month 2), Day 85 (Month 3), Day 180 (Month 6), Day 365 (Month 12) and Day 545 (Month 18)

Eligibility Module

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:

Randomization into higher dose group in the Main Study Phase
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;
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:
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:

Subject met an individual stopping criterion during the Main Study Phase;
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;
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;
Subject has developed a neuroinflammatory or autoimmune disease, including Guillain Barré Syndrome;
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;
Subject has developed anaphylaxis or severe allergic reactions;
Subject has developed allergic reactions to one of the components of the vaccine;
Subject has developed a malignancy;
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;
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;
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;
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;
Subject has been 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, sibling).

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Consulting, LLC		Milford	Connecticut	06460	United States
Stamford Therapeutics Consortium

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39029481	Derived	Ghadge SK, Schneider M, Dubischar K, Wagner L, Kadlecek V, Obersriebnig M, Hochreiter R, Klingler A, Larcher-Senn J, Derhaschnig U, Bender W, Eder-Lingelbach S, Bezay N. Immunogenicity and safety of an 18-month booster dose of the VLA15 Lyme borreliosis vaccine candidate after primary immunisation in healthy adults in the USA: results of the booster phase of a randomised, controlled, phase 2 trial. Lancet Infect Dis. 2024 Nov;24(11):1275-1286. doi: 10.1016/S1473-3099(24)00372-4. Epub 2024 Jul 16.
38830375

Label	URL
To obtain contact information for a study center near you, click here.	View source

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	VLA15 With Alum Lower Dose	Main Study Phase: VLA15 with Alum lower dose - Booster Phase: arm discontinued VLA15: a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate.
FG001	VLA15 With Alum Higher Dose	Main Study Phase: VLA15 with Alum higher dose - Booster Phase: VLA15 higher dose or placebo VLA15: a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate.
FG002	Placebo	Main Study Phase: placebo - Booster phase: arm discontinued Placebo: PBS (Phosphate Buffered Saline).
FG003	Booster Phase: VLA15 With Alum Higher Dose	Participants who received higher dose of VLA15 with alum in main study phase were randomized to receive a single booster dose of VLA15 with alum higher dose vaccine at Month 18 in booster phase.
FG004	Booster Phase: Placebo	Participants who received higher dose of VLA15 with alum in main study phase were randomized to receive a single dose of placebo at Month 18 in booster phase.

Periods

Title

Milestones

Reasons Not Completed

Main Study Phase (18 Months)

Type	Comment	Milestone Data
STARTED		FG00097 subjects FG00198 subjects FG00251 subjects FG0030 subjects FG004
COMPLETED	Participants who completed Day 545 (Month 18)	FG00089 subjects FG00184 subjects FG00246 subjects FG0030 subjects
NOT COMPLETED		FG0008 subjects FG00114 subjects FG0025 subjects FG0030 subjects FG004

Type	Comment	Reasons
Withdrawal by Subject		FG0000 subjects FG0017 subjects FG0022 subjects FG003

Booster Phase (Approx. 12 Months)

Type	Comment	Milestone Data
STARTED		FG0000 subjectsParticipants did not continue booster phase. FG0010 subjectsParticipants who continued to booster phase are reported under booster phase arms. FG0020 subjectsParticipants did not continue booster phase. FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	VLA15 With Alum Lower Dose	0.75 ml injection of VLA15 w/ alum applied at Days 1, 57, and 180 in the Main study phase. VLA15 is a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate. Participants of this arm did not enter booster phase.
BG001	VLA15 With Alum Higher Dose

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous		Here, number analyzed signifies number of participants evaluable for specified rows.

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

GMTs for IgG Against Each OspA Serotype

Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) against each Outer Surface Protein A (OspA) serotype ST1 to ST6, determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 208 (Month 7)

Per-protocol population, excluded those participants with at least one relevant protocol deviation (i.e., a protocol deviation with possible impact on immunogenicity). Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Geometric Mean

95% Confidence Interval

Units per milliliter (U/mL)

Day 208 (Month 7)

ID	Title	Description
OG000	VLA15 With Alum Lower Dose	Main Study Phase: VLA15 with Alum lower dose - Booster Phase: arm discontinued VLA15: a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Main Study Phase: VLA15 With Alum Lower Dose	0.75 ml injection of VLA15 w/ alum applied at Days 1, 57, and 180. VLA15 is a multivalent recombinant Outer Surface Protein A (OspA) based vaccine candidate.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)		Non-systematic Assessment	MedDRA v24.0 was used for Main Study Phase (VLA15 lower dose, higher dose and placebo). MedDRA v25.0 was used for Booster Phase (VLA15 higher dose and placebo).

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Injection site pain	General disorders		Systematic Assessment	Includes systematic and non-systematic assessments. MedDRA v24.0 was used for Main Study Phase (VLA15 lower dose, higher dose and placebo). MedDRA v25.0 was used for Booster Phase (VLA15 higher dose and placebo).

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Director Clinical Strategy	Valneva Austria GmbH	+43120620	0	office@valneva.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 2, 2021	Mar 24, 2023	Prot_002.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jul 14, 2020	May 5, 2021	SAP_001.pdf

Submission Tracking

Condition Browse Module

ID	Term
D008193	Lyme Disease

ID	Term
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

No participants were enrolled in this arm during the main study phase.

FG0040 subjectsNo participants were enrolled in this arm during the main study phase.

Title	Measurements
	BG00138.8± 13.50 BG00338.8± 13.50

Title	Measurements
Female	BG0000 BG0017 BG0020 BG0037
Male	BG0000 BG00112 BG0020 BG00312

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020 BG0030
Asian	BG0000 BG0010 BG0020 BG0030
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020 BG0030
Black or African American	BG0000 BG0010 BG0020 BG0030
White	BG0000 BG00119 BG0020 BG00319
More than one race	BG0000 BG0010 BG0020 BG0030
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030

OG00021.4(19.8 to 23.1)

OG00120.2(19.8 to 20.6)

OG00221.8(19.6 to 24.1)

OG0002.4(0.7 to 8.4)

OG0011.2(0.2 to 6.3)

OG0022.3(0.4 to 12.1)

OG0001.0(1.0 to 1.1)

OG0011.0(1.0 to 1.0)

OG0021.0(1.0 to 1.1)

OG00020.8(19.3 to 22.4)

OG00120.3(19.7 to 20.9)

OG00221.2(19.5 to 23.1)

OG00022.6(19.0 to 26.8)

OG00120.0(20.0 to 20.0)

OG00223.1(16.9 to 31.5)

OG0001.9(0.3 to 9.9)

OG0011.8(0.3 to 9.3)

OG0020.0(0.0 to 11.4)

OG0003.3(0.6 to 16.7)

OG0010.0(0.0 to 11.7)

OG0027.7(1.4 to 33.3)

OG0001.0(1.0 to 1.1)

OG0011.0(1.0 to 1.0)

OG0021.0(1.0 to 1.0)

OG0001.0(0.9 to 1.1)

OG0011.0(1.0 to 1.0)

OG0021.1(0.9 to 1.2)

OG0003.1(0.9 to 10.7)

OG0013.1(0.9 to 10.7)

OG0020.0(0.0 to 10.7)

OG00120.0(20.0 to 20.0)

OG0010.0(0.0 to 17.6)

OG0011.0(1.0 to 1.0)

OG0010.1(0.0 to 0.1)

OG0011.0(1.0 to 1.0)

OG00120.0(20.0 to 20.0)

OG0010.0(0.0 to 22.8)

OG0010.0(0.0 to 43.4)

OG00131.6(15.4 to 54.0)

OG0010.0(0.0 to 21.5)