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

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)

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.

Study Overview

• Status: Completed
• Conditions: High Grade Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Biological: VB10.16 Immunotherapy (DNA vaccine)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Hamburg, Lower Saxony, Germany, 20246
      • Universitätsklinikum Hamburg-Eppendorf
    • Hannover, Lower Saxony, Germany, 30625
      • Medical School Hanover
    • Wolfsburg, Lower Saxony, Germany, 38440
      • Klinikum Wolfsburg
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • IZD Institut für Zytologie und Dysplasie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria (abbreviated):

1. Women ≥18 years

2. 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)

3. Satisfactory colposcopic examination.

Exclusion Criteria (abbreviated):

1. More than 2 cervical quadrants of CIN 3 as visualised by colposcopy.
2. 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.
3. Current severe pelvic inflammatory disease, severe cervicitis, or other severe gynaecological infection as per colposcopy and clinical examination.
4. Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV).
5. Administration of any blood product within 3 months of enrolment.
6. Concomitant or prior malignant disease.
7. Clinically significant autoimmune disease.
8. Known allergy to Kanamycin or other aminoglycosides
9. Known immunodeficiency and or immunosuppression.
10. History of toxic shock syndrome.
11. Evidence or history of clinically significant cardiac disease
12. Active infection requiring parenteral antibiotics.
13. Tattoos, scars, or active lesions/rashes within 2 cm of the site of vaccination or any implantable leads.
14. Immunosuppression
15. Major surgery within 3 months of trial entry.
16. Current or recent (within 30 days of first study treatment) participation in a clinical trial.
17. Previous vaccination (either therapeutic and/or prophylactic) against HPV.
18. Administration of any live vaccine within 90 days of trial entry.
19. Concomitant anticancer therapies.
20. Inadequate bone marrow function
21. Inadequate liver function
22. Clinical significant electrolyte abnormalities
23. Women of childbearing age not willing to use an effective form of contraception
24. Pregnancy or intention to become pregnant
25. Nursing women
26. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 3mg VB10.16 Vaccine; 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); 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.; Other Names: Biological/Vaccine
Experimental: Cohort 2: 3mg VB10.16 Vaccine; 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); 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.; Other Names: Biological/Vaccine

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Nykode Therapeutics ASA
• Collaborators: Theradex; Vaccibody AS
• Investigators: Study Director: Irene Skjørestad, MSc, Vaccibody AS

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 19, 2015
• First Posted (Estimate): August 20, 2015

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; Human Papillomavirus; CIN 2/3; HSIL; Therapeutic DNA vaccine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VB C-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No