High grade cervical intraepithelial neoplasia (HSIL, CIN 2/3)
Conditions
Interventions
Product Name: VB10.16
Pharmaceutical Form: Solution for injection
INN or Proposed INN: VB10.16
Current Sponsor code: VB10.16
Concentrati
Sponsors
VACCIBODY A.S.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women =18 years who, after counselling by their clinicians consider the risk to future pregnancies from treating cervical abnormalities to outweigh the risk of developing cancer during observation of those abnormalities. In this context no specific upper age threshold is intended at the time of clinical trial entry. 2. Women with ectocervical HPV16+ associated High Grade Cervical Intraepithelial Neoplasia as verified by local pathology (biopsy) obtained within four weeks prior to start of treatment. 2.1. Dosing Phase: Women with histologically confirmed HPV16+ associated CIN 2 high grade Cervical Intraepithelial Neoplasia (HSIL; CIN 2). 2.2. Expansion Phase: Women with histologically confirmed HPV16+ associated CIN 2/3 high grade Cervical Intraepithelial Neoplasia (HSIL; CIN 2/3). 3. Satisfactory colposcopic examination documented with colpo-photography (digital Photography) defined as: 3.1. Visibility of the entire transformation zone including the squamocolumnar junction. 3.2. Visibility of the entire lesion margin. 4. ECOG performance status = 1. 5. Written informed consent. 6. Has agreed to the mandatory biological sampling schedule in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: Concomitant conditions 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, with exception of adequately treated basal cell carcinoma or other non-melanomatous skin cancer, low grade bladder cancer or other malignancies treated with curative intent 2 or more years pre study entry and in remission at study entry. 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 including congestive heart failure, unstable angina, acute myocardial infarction or cerebrovascular accident within the last six months, and symptomatic arrhythmia requiring therapy (with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation). 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. Current and prior treatment 14. Immunosuppression including the continued use of systemic or topical steroids at or near the injection site [deltoid, upper arm] (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents for any concurrent condition. All other corticosteroids must be discontinued > 4 weeks prior to first study vaccine administration. 15. Major surgery within 3 months of trial entry. 16. Current or recent (within 30 days of the first study treatment) participation in a clinical trial or treatment with another investigation medicinal product. 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. Haematology, coagulation and biochemistry: 20. Inadequate bone marrow function: 20.1. Absolute Lymphocyte count: 1.5 x the Upper Limit of Normal (ULN) for the institution. 21.2. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) >3.0 x ULN. 21.3. Alkaline phosphatase levels >5.0 x ULN. 22. Clinically significant uncorrected electrolyt
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To assess immunogenicity of 3 mg/ml VB10.16 immunotherapy in patients with HPV16+ Cervical Intraepithelial Neoplasia Grade 2/3 (HSIL; CIN 2/3). • To make a preliminary assessment of efficacy of VB10.16 immunotherapy. ;Primary end point(s): The percentage of patients with adverse events (AEs), including any dose-limiting toxicities (DLT), laboratory assessments and physical findings.;Main Objective: To assess the safety/tolerability of 3 mg/ml VB10.16 immunotherapy in patients with HPV16+ Cervical Intraepithelial Neoplasia Grade 2/3 (HSIL; CIN 2/3).; Timepoint(s) of evaluation of this end point: AEs - from time of signing the informed consent form until 30 days after the final vaccination, unless a causal relationship to treatment is suspected. DLT - All CTCAE Grade 3 and 4 toxicities which are clinically unexpected and causally related to VB10.16 and occur within 30 days of the last vaccination. Haematology/biochemistry done at screening, week 1, week 16 and week 24. Coagulation done at screening and week 1. Physical exam and vital signs done at screening, week 1, week 8, week 16 and week 24. ECG done at screening. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The monitoring of immune response by means of: - 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. • The percentage of patients with HPV16+ clearance. • The percentage of patients with lesion regression (Lesion regression is defined as a regression from CIN 3 or CIN 2 [HSIL; high grade] at baseline to CIN1 or less [LSIL; low grade or normal] at any time during the study). ; Timepoint(s) of evaluation of this end point: Immune response at week 1 and at pre-specified timepoints up to week 24. HPV16+ COBAS testing done at screening, week 8, week 16 and week 24. Colposcopy (+ digital photography) done at screening, (or at week 1), week 8, week 16 and week 24. Liquid Based Cytology done at screening, week 8, week 16 and week 24. Biopsies and IHC done at screening and week 24. Week 16 biopsies will be done if sufficient tissue can be taken from the lesion. | — |
Countries
Germany
Contacts
Public ContactClinical Operations
Theradex (Europe) Ltd
Outcome results
None listed