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Safety, Reactogenicity and Immunogenicity of Adenovirus Serotype 26 (Ad26)- and Modified Vaccinia Ankara (MVA)-Vectored Vaccine Components in Otherwise Healthy Women With HPV16 or HPV18 Infection of the Cervix

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ClinicalTrials.gov Identifier: NCT03610581
Recruitment Status : Terminated (Low enrolment and increasing COVID restrictions, following an earlier enrolment pause in April made it clear that completion of the study would not be feasible)
First Posted : August 1, 2018
Results First Posted : November 9, 2021
Last Update Posted : November 24, 2021
Sponsor:
Collaborator:
Bavarian Nordic
Information provided by (Responsible Party):
Janssen Vaccines & Prevention B.V.

Tracking Information
First Submitted Date  ICMJE July 26, 2018
First Posted Date  ICMJE August 1, 2018
Results First Submitted Date  ICMJE October 11, 2021
Results First Posted Date  ICMJE November 9, 2021
Last Update Posted Date November 24, 2021
Actual Study Start Date  ICMJE September 27, 2018
Actual Primary Completion Date October 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
  • Number of Participants With Solicited Local Adverse Events (AEs) [ Time Frame: Up to 7 days after each vaccination (Up to Day 64) ]
    Number of participants with solicited local AEs were reported. Solicited local AE's included pain/tenderness, erythema, and induration/swelling.
  • Number of Participants With Solicited Systemic AEs [ Time Frame: Up to 7 days after each vaccination (Up to Day 64) ]
    Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included headache, fatigue, myalgia, arthralgia, chills, and fever.
  • Number of Participants With Unsolicited AEs [ Time Frame: 28 days after each vaccination (Up to Day 85) ]
    Number of participants with unsolicited AEs were reported. Unsolicited AEs included all AEs for which the participant was not specifically questioned in the participant diary.
  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months after the first vaccination (target visit Day 366) ]
    Number of participants with SAEs were reported. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
  • Percentage of Participants with Solicited Local and Systemic Adverse Events (AEs) [ Time Frame: 7 Days after each vaccination (approximately up to Day 64) ]
    Solicited local AEs: pain/tenderness, erythema, and induration/swelling. Solicited systemic AEs: headache, fatigue, myalgia, arthralgia, chills and fever.
  • Percentage of Participants with Unsolicited AEs [ Time Frame: 28 Days after each vaccination (approximately up to Day 85) ]
    Unsolicited AEs will include all AEs for which the participant is not specifically questioned in the participant diary.
  • Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Approximately up to Month 12 ]
    SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2021)
  • Percentage of Participants With Human Papillomavirus (HPV)-Specific CD4+ T-cell Responses: Interferon (IFN)g+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD4+ T-cell responses for IFNg+ to peptide pools were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
  • Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Interleukin (IL)2+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD4+ T-cell responses for IL2+ were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
  • Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Tumor Necrosis Factor (TNF)a+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD4+ T-cell responses for TNF a+ were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
  • Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IFNg+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD8+ T-cell responses for IFNg+ were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
  • Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IL2+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD8+ T-cell responses for IL2+ were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
  • Percentage of Participants With HPV-Specific CD8+ T-cell Responses: TNFa+ [ Time Frame: Day 57, Day 78, Day 239, and Day 366 ]
    Percentage of participants with HPV-Specific CD8+ T-cell responses for TNFa+ were reported. Cellular immunogenicity was measured by intracellular cytokine staining (ICS), allowing characterization of individual CD4 and CD8 T cell immune responses to vaccination. The different peptide pools for HPV16 or HPV 18 were: E2, E6/E7 and combined (E2 and E6/E7 both).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
Percentage of Participants with Human Papillomavirus (HPV)-Specific CD4+ and CD8+ T-Cell Responses [ Time Frame: 21 Days after last vaccination (approximately Day 78) ]
Expression of cytokines (for example [e.g.] interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], interleukin [IL]-2) by CD4+ and CD8+ T cell subsets will be determined by flow cytometry.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Reactogenicity and Immunogenicity of Adenovirus Serotype 26 (Ad26)- and Modified Vaccinia Ankara (MVA)-Vectored Vaccine Components in Otherwise Healthy Women With HPV16 or HPV18 Infection of the Cervix
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, First-in-Human, Phase 1/2a Study to Evaluate Safety, Reactogenicity and Immunogenicity of Monovalent HPV16 and HPV18 Ad26-vectored Vaccine Components and an MVA-vectored HPV16/18 Vaccine Component in Otherwise Healthy Women With HPV16 or 18 Infection of the Cervix
Brief Summary The main purpose of this study is to assess safety and reactogenicity of the 3 vaccine regimens.
Detailed Description This study is part of a vaccine program which aims to generate a therapeutic vaccine for women with HPV types 16 or 18 infection, with a focus on early disease interception. The study consists of 3 periods: Screening period of up to 42 days (6 weeks), followed by prime and boost immunizations and follow-up visits up to 12 months after the first vaccination. Evaluation of the safety/reactogenicity of the vaccine regimens will include physical assessment by study-site personnel, participant reports on signs and symptoms and laboratory assessments following vaccinations. Immunogenicity and Virology/Histology assessments will also be performed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Human Papillomavirus Infections
Intervention  ICMJE
  • Biological: Ad26.HPV16
    Participants will receive Ad26.HPV16 as a solution for intramuscular injection.
    Other Name: JNJ-63682918
  • Biological: Ad26.HPV18
    Participants will receive Ad26.HPV18 as a solution for intramuscular injection.
    Other Name: JNJ-63682931
  • Biological: MVA.HPV16/18
    Participants will receive MVA.HPV16/18 as a solution for intramuscular injection.
    Other Name: JNJ-65195208
  • Biological: Placebo
    Participants will receive matched placebo as a solution for intramuscular injection.
Study Arms  ICMJE
  • Experimental: Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
    Participants will receive a dose of adenovirus serotype 26 (Ad26)-human papillomavirus (HPV)16 or HPV18 (Ad26.HPV16 or Ad26.HPV18) as prime immunization and a dose of Modified Vaccinia Ankara (MVA)-HPV16/18 (MVA.HPV16/18) as boost immunization.
    Interventions:
    • Biological: Ad26.HPV16
    • Biological: Ad26.HPV18
    • Biological: MVA.HPV16/18
  • Experimental: Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18
    Participants will receive a double dose of Ad26.HPV16 or Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
    Interventions:
    • Biological: Ad26.HPV16
    • Biological: Ad26.HPV18
    • Biological: MVA.HPV16/18
  • Experimental: Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18
    Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.
    Interventions:
    • Biological: Ad26.HPV16
    • Biological: Ad26.HPV18
    • Biological: MVA.HPV16/18
  • Placebo Comparator: Control: Placebo
    Participants will receive matched placebo as prime and boost immunizations.
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 24, 2020)
9
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2018)
66
Actual Study Completion Date  ICMJE October 15, 2020
Actual Primary Completion Date October 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • Must have an human papillomavirus (HPV) type 16 or 18 infection of the cervix as determined by a qualitative PCR test within 8 weeks prior to screening or at the time of screening. Available history of high-risk (HR)-HPV positivity and HPV16 or HPV18 positivity positivity will be recorded
  • Must have a recent colposcopy result (with a maximum of 12 months old at screening); in case a colposcopy has not been performed before, it will be done as screening procedure
  • Contraceptive (birth control) use by participants should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
  • Agrees not to donate blood until 3 months after receiving the last dose of study vaccine

Exclusion Criteria:

  • In case cytology results are available, participant has current or history of high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS) or any high-grade vulvar, vaginal or anal intraepithelial neoplasia
  • Current or history of cervical intraepithelial neoplasia (CIN)2+ or cervical cancer
  • Confirmed co-infection with both HPV16 and HPV18
  • History of an underlying clinically significant acute or chronic medical condition, other than infection with HPV, or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
  • Tests positive for human immunodeficiency virus (HIV) at screening
  • Chronic active hepatitis B or hepatitis C infection, verified at screening by hepatitis B surface antigen or anti-hepatitis C virus antibody, respectively
  • Vaginal atrophy with or without topical hormonal therapies or systemic selective estrogen receptor modulators
  • Exposed to at least 1 dose of an HPV prophylactic vaccine or participant has participated in the past in another preventive or therapeutic HPV vaccine study
  • Clinically significant gynecological abnormalities that could, in the judgment of the investigator, interfere with study evaluation (for example [e.g.], prolapse, myoma, fibroid, hysterectomy)
  • Symptomatic vaginal or genital infection (including genital herpes) as confirmed by physician or investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT03610581
Other Study ID Numbers  ICMJE CR108458
2018-000200-41 ( EudraCT Number )
VAC81623HPV1002 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Vaccines & Prevention B.V.
Study Sponsor  ICMJE Janssen Vaccines & Prevention B.V.
Collaborators  ICMJE Bavarian Nordic
Investigators  ICMJE
Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial Janssen Vaccines & Prevention B.V.
PRS Account Janssen Vaccines & Prevention B.V.
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP