An Exploratory Safety and Immunogenicity Study of HPV16+ Immunotherapy VB10.16 in Women With HSIL; CIN 2/3)

Study Overview
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Brief Summary
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This is an exploratory, open, prospective multi-centre study of VB10.16 immunotherapy in patients with high grade HPV16+ Cervical Intraepithelial Neoplasia (HSIL; CIN2/3). This study will recruit approximately 27-40 female patients with high grade cervical intraepithelial neoplasia (HSIL, CIN 2/3) at multiple sites in Europe.

Detailed Description
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The study will be divided into two phases, a dosing and expansion phase. During the dosing phase the safety, tolerability and immunogenicity of 2 different vaccination schedules of 3 mg VB10.16 immunotherapy will be established in a minimum of 12 patients with histology confirmed CIN 2. During the expansion phase the safety, tolerability and immunogenicity of the selected vaccination schedule will be evaluated in approximately 15 to 20 patients with histology confirmed HPV16+ CIN 2/3.

Official Title
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An Exploratory Safety and Immunogenicity Study of Human Papillomavirus (HPV16+) Immunotherapy VB10.16 in Women With High Grade Cervical Intraepithelial Neoplasia (HSIL; CIN 2/3)

Conditions
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High Grade Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: VB10.16 Immunotherapy (DNA vaccine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (abbreviated): Women ≥18 years Women with ectocervical HPV16+ associated High Grade Cervical Intraepithelial Neoplasia (HSIL) as verified by local pathology: (Dosing Phase: Women with histologically confirmed HPV16+ associated CIN 2; Expansion Phase: Women with histologically confirmed HPV16+ associated CIN 2/3) Satisfactory colposcopic examination. Exclusion Criteria (abbreviated): More than 2 cervical quadrants of CIN 3 as visualised by colposcopy. Atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology, malignant cells on cytology or histology or other suspicion of either micro-invasive or invasive disease. Current severe pelvic inflammatory disease, severe cervicitis, or other severe gynaecological infection as per colposcopy and clinical examination. Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV). Administration of any blood product within 3 months of enrolment. Concomitant or prior malignant disease. Clinically significant autoimmune disease. Known allergy to Kanamycin or other aminoglycosides Known immunodeficiency and or immunosuppression. History of toxic shock syndrome. Evidence or history of clinically significant cardiac disease Active infection requiring parenteral antibiotics. Tattoos, scars, or active lesions/rashes within 2 cm of the site of vaccination or any implantable leads. Immunosuppression Major surgery within 3 months of trial entry. Current or recent (within 30 days of first study treatment) participation in a clinical trial. Previous vaccination (either therapeutic and/or prophylactic) against HPV. Administration of any live vaccine within 90 days of trial entry. Concomitant anticancer therapies. Inadequate bone marrow function Inadequate liver function Clinical significant electrolyte abnormalities Women of childbearing age not willing to use an effective form of contraception Pregnancy or intention to become pregnant Nursing women Evidence of any other medical condition that may interfere with study participation, patient compliance or place the patient at high risk from treatment-related complications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 3mg VB10.16 Vaccine<br>VB10.16 Immunotherapy (DNA vaccine): Biological/Vaccine Vaccination time points: Week 0, Week 3, Week 6, 3mgs per vaccination | Biological: VB10.16 Immunotherapy (DNA vaccine)<br>* Patients will receive 3 vaccinations of 3 mg VB10.16 at the pre-specified time points. VB10.16 will be administered intramuscularly in the area over the lateral deltoid muscle.<br>* Other names: Biological/Vaccine;|
| Experimental: Cohort 2: 3mg VB10.16 Vaccine<br>VB10.16 Immunotherapy (DNA vaccine): Biological/Vaccine Vaccination time points: Week 0, Week 4, Week 8, 3mgs per vaccination | Biological: VB10.16 Immunotherapy (DNA vaccine)<br>* Patients will receive 3 vaccinations of 3 mg VB10.16 at the pre-specified time points. VB10.16 will be administered intramuscularly in the area over the lateral deltoid muscle.<br>* Other names: Biological/Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/tolerability | - The percentage of patients with adverse events (AEs), including any dose-limiting toxicities (DLT), laboratory assessments and physical findings. | 6 months (extended follow up for additional 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | The percentage of patients with E6/E7 specific cellular immune response in the blood. The percentage of patients with cellular immune response in the target lesions. The percentage of patients with humoral response against the E6/E7 viral antigen. | 6 months | 
| Preliminary assessment of efficacy | The percentage of patients with HPV16+ clearance. The percentage of patients with lesion regression | 6 months (extended follow up for additional 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSIL, CIN 2/3, Therapeutic DNA vaccine, Human Papillomavirus, Immunotherapy