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

High Grade Cervical Intraepithelial Neoplasia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02529930
• Other study ID #: VB C-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2015
• Est. completion date: January 31, 2019

Study information

• Verified date: July 2022
• Source: Nykode Therapeutics ASA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• High Grade Cervical Intraepithelial Neoplasia
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg	Lower Saxony
Germany	IZD Institut für Zytologie und Dysplasie	Hannover	Niedersachsen
Germany	Medical School Hanover	Hannover	Lower Saxony
Germany	Klinikum Wolfsburg	Wolfsburg	Lower Saxony

Sponsors (3)

Lead Sponsor	Collaborator
Nykode Therapeutics ASA	Theradex, Vaccibody AS

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)