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

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

The main purpose of this study is to assess safety and reactogenicity of the 3 vaccine regimens.

Study Overview

• Status: Terminated
• Conditions: Human Papillomavirus Infections
• Intervention / Treatment: Biological: Ad26.HPV16; Biological: Ad26.HPV18; Biological: MVA.HPV16/18; Biological: Placebo

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: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• United States
  • Florida
    • Doral, Florida, United States, 33166
      • Doral Medical Research
    • Fort Myers, Florida, United States, 33912
      • Clinical Physiology Associates
    • Miami, Florida, United States, 33174
      • Florida Research Center Inc.
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • VGR & NOCCR - Knoxville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Ad26.HPV16; Participants will receive Ad26.HPV16 as a solution for intramuscular injection.; Other Names: JNJ-63682918; Biological: Ad26.HPV18; Participants will receive Ad26.HPV18 as a solution for intramuscular injection.; Other Names: JNJ-63682931; Biological: MVA.HPV16/18; Participants will receive MVA.HPV16/18 as a solution for intramuscular injection.; Other Names: JNJ-65195208
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.	Biological: Ad26.HPV16; Participants will receive Ad26.HPV16 as a solution for intramuscular injection.; Other Names: JNJ-63682918; Biological: Ad26.HPV18; Participants will receive Ad26.HPV18 as a solution for intramuscular injection.; Other Names: JNJ-63682931; Biological: MVA.HPV16/18; Participants will receive MVA.HPV16/18 as a solution for intramuscular injection.; Other Names: JNJ-65195208
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.	Biological: Ad26.HPV16; Participants will receive Ad26.HPV16 as a solution for intramuscular injection.; Other Names: JNJ-63682918; Biological: Ad26.HPV18; Participants will receive Ad26.HPV18 as a solution for intramuscular injection.; Other Names: JNJ-63682931; Biological: MVA.HPV16/18; Participants will receive MVA.HPV16/18 as a solution for intramuscular injection.; Other Names: JNJ-65195208
Placebo Comparator: Control: Placebo; Participants will receive matched placebo as prime and boost immunizations.	Biological: Placebo; Participants will receive matched placebo as a solution for intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local Adverse Events (AEs)	Number of participants with solicited local AEs were reported. Solicited local AE's included pain/tenderness, erythema, and induration/swelling.	Up to 7 days after each vaccination (Up to Day 64)
Number of Participants With Solicited Systemic AEs	Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included headache, fatigue, myalgia, arthralgia, chills, and fever.	Up to 7 days after each vaccination (Up to Day 64)
Number of Participants With Unsolicited AEs	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.	28 days after each vaccination (Up to Day 85)
Number of Participants With Serious Adverse Events (SAEs)	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.	Up to 12 months after the first vaccination (target visit Day 366)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Human Papillomavirus (HPV)-Specific CD4+ T-cell Responses: Interferon (IFN)g+	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).	Day 57, Day 78, Day 239, and Day 366
Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Interleukin (IL)2+	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).	Day 57, Day 78, Day 239, and Day 366
Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Tumor Necrosis Factor (TNF)a+	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).	Day 57, Day 78, Day 239, and Day 366
Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IFNg+	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).	Day 57, Day 78, Day 239, and Day 366
Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IL2+	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).	Day 57, Day 78, Day 239, and Day 366
Percentage of Participants With HPV-Specific CD8+ T-cell Responses: TNFa+	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).	Day 57, Day 78, Day 239, and Day 366

Collaborators and Investigators

• Sponsor: Janssen Vaccines & Prevention B.V.
• Collaborators: Bavarian Nordic

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Actual): October 15, 2020
• Study Completion (Actual): October 15, 2020

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Infections; Communicable Diseases; Papillomavirus Infections
• Other Study ID Numbers: CR108458; 2018-000200-41 (EudraCT Number); VAC81623HPV1002 (Other Identifier: Janssen Vaccines & Prevention B.V.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No