search
Back to results

Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma (VECTOR)

Primary Purpose

Moderate to Severe Asthma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tezepelumab
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Moderate to Severe Asthma focused on measuring Tezepelumab, Humoral Immune Response, Quadrivalent Influenza Vaccination, Antibody response, Subcutaneous

Eligibility Criteria

12 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented physician-diagnosed asthma for at least 12 months prior to Visit 1.
  • Morning pre-bronchodilator FEV1 (Forced expiratory volume) of > 50% predicted normal value at Visit 1 or Visit 2.
  • Body weight ≥ 40 kg.
  • For women of childbearing potential, a negative urine pregnancy test is required prior to administration of study intervention at Visit 3.
  • Must have 'not well-controlled' asthma.

Exclusion Criteria:

  • Clinically important pulmonary disease other than asthma.
  • Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment.
  • Life-threatening asthma
  • History of cancer.
  • Allergy to eggs, if egg based influenza vaccine will be administered.
  • History of anaphylaxis to any biologic therapy.
  • Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack-years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to Visit 1 to be eligible.
  • History of alcohol or drug abuse within 12 months prior to the date of informed consent.
  • Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures during the conduct of the study.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tezepelumab

Placebo to Tezepelumab

Arm Description

Participants will be randomized to receive tezepelumab 210 mg administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.

Participants will be randomized to receive placebo SC Q4W, administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.

Outcomes

Primary Outcome Measures

Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs)
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs)
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Post-vaccination Strain-specific Serum MN Antibody GMTs
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in HAI Antibody Titer
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in MN Antibody Titer
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. Vaccine immunogenicity analysis set consisted of all randomised patients who received the influenza vaccine plus at least 1 dose of tezepelumab or placebo, had pre and post vaccination HAI or MN antibody measurements, had no influenza infection prior to Visit 7 (Week 16), and had no protocol deviation, judged to have the potential to interfere with the generation or interpretation of an antibody response.
Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.

Secondary Outcome Measures

Serum Tezepelumab Concentrations
Tezepelumab serum concentrations were summarized using descriptive statistics at each visit.
Immunogenicity
Immunogenicity assessments were performed. ADA prevalence was defined as patients who are ADA positive at any time including baseline. Persistently positive was defined as having at least two post-baseline ADA positive measurements (with ≥16 weeks between first and last positive) or an ADA positive result at the last available post-baseline assessment. Transiently positive was defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Treatment boosted ADA was defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment. Treatment emergent ADA (ADA incidence) was defined as the sum of treatment induced ADA and treatment boosted ADA.

Full Information

First Posted
August 23, 2021
Last Updated
June 20, 2023
Sponsor
AstraZeneca
Collaborators
Amgen
search

1. Study Identification

Unique Protocol Identification Number
NCT05062759
Brief Title
Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma
Acronym
VECTOR
Official Title
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Potential Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Adolescent and Young Adult Participants With Moderate to Severe Asthma (VECTOR)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
August 23, 2021 (Actual)
Primary Completion Date
March 21, 2022 (Actual)
Study Completion Date
July 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 3b, multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of tezepelumab (210 mg subcutaneous [SC] every 4 weeks [Q4W]) on antibody responses following seasonal quadrivalent influenza virus vaccination in the fall/winter 2021-2022 in the USA.
Detailed Description
Participants with moderate to severe asthma will enter the screening period of a minimum of 2 weeks to allow adequate time for all of the eligibility criteria to be evaluated. They will be randomized 1:1 to receive tezepelumab 210 mg or placebo SC Q4W, administered at Weeks 0, 4, 8 and 12. Randomization will be monitored to ensure at least 50% of the randomized participants are between the ages of 12 to 17 years. Participants will receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention. Serum samples for evaluation of antibody response will be drawn at Week 12 (pre-vaccination) and at Week 16 (4 weeks post-vaccination) when humoral response to the vaccination is expected to be fully developed. The End of Treatment (EOT) Visit will be conducted at Week 16 and a final Follow-up Visit and the End of Study Visit will be conducted at Week 28.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moderate to Severe Asthma
Keywords
Tezepelumab, Humoral Immune Response, Quadrivalent Influenza Vaccination, Antibody response, Subcutaneous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Neither the participant nor any of the investigators or sponsor staff who are involved in the treatment or clinical evaluation and monitoring of the participants will be aware of the treatment received. Since tezepelumab and placebo are not visually distinct, study intervention will be handled by a qualified person (eg, pharmacist or study nurse) at the site.
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tezepelumab
Arm Type
Experimental
Arm Description
Participants will be randomized to receive tezepelumab 210 mg administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.
Arm Title
Placebo to Tezepelumab
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to receive placebo SC Q4W, administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.
Intervention Type
Drug
Intervention Name(s)
Tezepelumab
Intervention Description
210 mg SC injection Q4W.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
SC injection Q4W.
Primary Outcome Measure Information:
Title
Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs)
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time Frame
From Week 12 to Week 16
Title
Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time Frame
From Week 12 to Week 16
Title
Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs)
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time Frame
Week 16
Title
Post-vaccination Strain-specific Serum MN Antibody GMTs
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time Frame
Week 16
Title
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in HAI Antibody Titer
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time Frame
Week 16
Title
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in MN Antibody Titer
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. Vaccine immunogenicity analysis set consisted of all randomised patients who received the influenza vaccine plus at least 1 dose of tezepelumab or placebo, had pre and post vaccination HAI or MN antibody measurements, had no influenza infection prior to Visit 7 (Week 16), and had no protocol deviation, judged to have the potential to interfere with the generation or interpretation of an antibody response.
Time Frame
Week 16
Title
Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time Frame
Week 16
Title
Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40
Description
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Serum Tezepelumab Concentrations
Description
Tezepelumab serum concentrations were summarized using descriptive statistics at each visit.
Time Frame
Week 0, Week 12, Week 16 and Week 28
Title
Immunogenicity
Description
Immunogenicity assessments were performed. ADA prevalence was defined as patients who are ADA positive at any time including baseline. Persistently positive was defined as having at least two post-baseline ADA positive measurements (with ≥16 weeks between first and last positive) or an ADA positive result at the last available post-baseline assessment. Transiently positive was defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Treatment boosted ADA was defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment. Treatment emergent ADA (ADA incidence) was defined as the sum of treatment induced ADA and treatment boosted ADA.
Time Frame
From Baseline to Week 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented physician-diagnosed asthma for at least 12 months prior to Visit 1. Morning pre-bronchodilator FEV1 (Forced expiratory volume) of > 50% predicted normal value at Visit 1 or Visit 2. Body weight ≥ 40 kg. For women of childbearing potential, a negative urine pregnancy test is required prior to administration of study intervention at Visit 3. Must have 'not well-controlled' asthma. Exclusion Criteria: Clinically important pulmonary disease other than asthma. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment. Life-threatening asthma History of cancer. Allergy to eggs, if egg based influenza vaccine will be administered. History of anaphylaxis to any biologic therapy. Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack-years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to Visit 1 to be eligible. History of alcohol or drug abuse within 12 months prior to the date of informed consent. Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures during the conduct of the study.
Facility Information:
Facility Name
Research Site
City
Bakersfield
State/Province
California
ZIP/Postal Code
93301
Country
United States
Facility Name
Research Site
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Research Site
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65203
Country
United States
Facility Name
Research Site
City
Northfield
State/Province
New Jersey
ZIP/Postal Code
08225
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45406
Country
United States
Facility Name
Research Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
Research Site
City
Edmond
State/Province
Oklahoma
ZIP/Postal Code
73034
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75225
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Facility Name
Research Site
City
Waco
State/Province
Texas
ZIP/Postal Code
76712
Country
United States
Facility Name
Research Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53228
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5180C00031&amp;attachmentIdentifier=30f0d69f-126e-4f79-8bc8-0542f713c2b0&amp;fileName=D5180C00031_CSR_Synopsis_Redacted.pdf&amp;versionIdentifier=
Description
CSR Synopsis_Redacted

Learn more about this trial

Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma

We'll reach out to this number within 24 hrs