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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

Primary Purpose

Human Papillomavirus Infections

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Ad26.HPV16

Ad26.HPV18

MVA.HPV16/18

Placebo

About this trial

This is an interventional treatment trial for Human Papillomavirus Infections

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18

Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18

Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18

Control: Placebo

Arm Description

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.

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.

Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.

Participants will receive matched placebo as prime and boost immunizations.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

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).

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).

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).

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).

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).

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).

Full Information

NCT ID

NCT03610581

First Posted

July 26, 2018

Last Updated

November 23, 2021

Sponsor

Janssen Vaccines & Prevention B.V.

Collaborators

Bavarian Nordic

1. Study Identification

Unique Protocol Identification Number

NCT03610581

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Terminated

Why Stopped

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

Study Start Date

September 27, 2018 (Actual)

Primary Completion Date

October 15, 2020 (Actual)

Study Completion Date

October 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Vaccines & Prevention B.V.

Collaborators

Bavarian Nordic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Human Papillomavirus Infections

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Regimen 1: Single Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18

Arm Type

Experimental

Arm Description

Arm Title

Regimen 2: Double Ad26.HPV16 or Ad26.HPV18 and MVA.HPV16/18

Arm Type

Experimental

Arm Description

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.

Arm Title

Regimen 3: Ad26.HPV16/Ad26.HPV18 mix and MVA.HPV16/18

Arm Type

Experimental

Arm Description

Participants will receive a mix of Ad26.HPV16/Ad26.HPV18 as prime immunization and a dose of MVA.HPV16/18 as boost immunization.

Arm Title

Control: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive matched placebo as prime and boost immunizations.

Intervention Type

Biological

Intervention Name(s)

Ad26.HPV16

Other Intervention Name(s)

JNJ-63682918

Intervention Description

Participants will receive Ad26.HPV16 as a solution for intramuscular injection.

Intervention Type

Biological

Intervention Name(s)

Ad26.HPV18

Other Intervention Name(s)

JNJ-63682931

Intervention Description

Participants will receive Ad26.HPV18 as a solution for intramuscular injection.

Intervention Type

Biological

Intervention Name(s)

MVA.HPV16/18

Other Intervention Name(s)

JNJ-65195208

Intervention Description

Participants will receive MVA.HPV16/18 as a solution for intramuscular injection.

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Participants will receive matched placebo as a solution for intramuscular injection.

Primary Outcome Measure Information:

Title

Number of Participants With Solicited Local Adverse Events (AEs)

Description

Number of participants with solicited local AEs were reported. Solicited local AE's included pain/tenderness, erythema, and induration/swelling.

Time Frame

Up to 7 days after each vaccination (Up to Day 64)

Title

Number of Participants With Solicited Systemic AEs

Description

Number of participants with solicited systemic AEs were reported. Solicited systemic AEs included headache, fatigue, myalgia, arthralgia, chills, and fever.

Time Frame

Up to 7 days after each vaccination (Up to Day 64)

Title

Number of Participants With Unsolicited AEs

Description

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.

Time Frame

28 days after each vaccination (Up to Day 85)

Title

Number of Participants With Serious Adverse Events (SAEs)

Description

Time Frame

Up to 12 months after the first vaccination (target visit Day 366)

Secondary Outcome Measure Information:

Title

Percentage of Participants With Human Papillomavirus (HPV)-Specific CD4+ T-cell Responses: Interferon (IFN)g+

Description

Time Frame