Clinical trial NCT03610581: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Human Papillomavirus Infections
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: Bavarian Nordic
First posted: 2018-08-01
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Solicited Local Adverse Events (AEs)
timeFrame: Up to 7 days after each vaccination (Up to Day 64)
measure: Number of Participants With Solicited Systemic AEs
timeFrame: Up to 7 days after each vaccination (Up to Day 64)
measure: Number of Participants With Unsolicited AEs
timeFrame: 28 days after each vaccination (Up to Day 85)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 12 months after the first vaccination (target visit Day 366)
Secondary outcomes:
measure: Percentage of Participants With Human Papillomavirus (HPV)-Specific CD4+ T-cell Responses: Interferon (IFN)g+
timeFrame: Day 57, Day 78, Day 239, and Day 366
measure: Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Interleukin (IL)2+
timeFrame: Day 57, Day 78, Day 239, and Day 366
measure: Percentage of Participants With HPV-Specific CD4+ T-cell Responses: Tumor Necrosis Factor (TNF)a+
timeFrame: Day 57, Day 78, Day 239, and Day 366
measure: Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IFNg+
timeFrame: Day 57, Day 78, Day 239, and Day 366
measure: Percentage of Participants With HPV-Specific CD8+ T-cell Responses: IL2+
timeFrame: Day 57, Day 78, Day 239, and Day 366
measure: Percentage of Participants With HPV-Specific CD8+ T-cell Responses: TNFa+
timeFrame: Day 57, Day 78, Day 239, and Day 366
Other outcomes:
Locations:
city: Doral
country: United States
facility: Doral Medical Research
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: Florida Research Center Inc.
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Newton
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Metairie
country: United States
facility: Medpharmics, LLC
state: Louisiana
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Knoxville
country: United States
facility: VGR & NOCCR - Knoxville
state: Tennessee
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References: