DEFLAGYN® Vaginal Gel and Spontaneous Remission and Regression of Unclear Cervical Smears and HPV High-risk Infections

Related Clinical Trial
Clinical, Translational and Biomarker-Based Female Genital HPV Induced Dysplasia and Cancer Screening Study Using Cf-HPV-DNA Blood Tests Diagnostic Cervical Conization for Persistent Infection or Integration of HPV DEFLAGYN® Vaginal Gel and Spontaneous Remission and Regression of Unclear Cervical Smears and HPV High-risk Infections A Study of ABI-2280 Vaginal Tablet in Participants With Cervical Intraepithelial Neoplasia A Study on the Immune Response and Safety of an Adjuvanted Human Papillomavirus Vaccine When Given to Healthy Women 16 to 26 Years of Age Predicting Response In Cervical Intraepithelial Neoplasia to Topical Imiquimod Treatment Cervical Cancer Screening Strategies DNA PAX1 and JAM3 Methylation for Cervical Cancer Screening The Organ Transplant Recipient HPV and Skin Cancer Study Effect of HPV Integration on Prognosis of Young Women With CIN2 in China Immunogenicity of Gardasil-9 HPV Vaccine in People Living With HIV Prevention and Screening Towards Elimination of Cervical Cancer HPV-based Screening Among Women 23-29 Years of Age Clinical Evaluation of Detection of High Risk HPV in Urine The Vaginal Microecology and Innate Immunity After Focused Ultrasound Ablation Treatment for CIN Large Loop Excision of the Transformation Zone (LLETZ) With vs Without IntraOperative Application of Lugol’s Iodine Evaluation of New Diagnostic Tool Using Fluorescence to Detect High-grade Vulvar Intraepithelial Neoplasia Optimization of Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico Low-cost Imaging Technology for Global Prevention of Cervical Cancer Biomarkers Predictive for Cervical Intraepithelial Neoplasia Grade 2 (CIN2) Evolvement The Durability of Protection and Immuno-persistence Study of a Recombinant HPV 16/18 Bivalent Vaccine in Female The Durability of Protection Study of a Recombinant HPV 16/18 Bivalent Vaccine in Female The Use of the LuViva Advanced Cervical Scan to Identify Women at High-Risk for Cervical Neoplasia Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application Extended VALidation of HUman Papillomavirus Assays and Collection DEvices for HPV Testing on Self-samples Conservative Management of HSIL in Patients With Future Pregnancy Aspiration Clinical Validation of Cervical Cancer Screening Methods Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women (HPV400) Virtual Reality: Influence on Satisfaction, Pain, and Anxiety in Patients Undergoing Colposcopy Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma Immuno-persistence Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls (54m) Pembrolizumab for the Treatment of High-Grade Vulvar, Vaginal, or Cervical Intraepithelial Neoplasia Self-Testing Options in the Era of Primary HPV Screening for Cervical Cancer Trial DNA Methylation Testing for the Screening of Uterine Cervical Lesion Immunohistochemical Staining of p16 for the Screening of Cervical Cancer CASUS: Validation for Detection of Precursor Lesions CASUS: Improved and Quality Assured Collection of First-void Urine Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL) Lugol’s Solution in Addition to Acetic Acid During Colposcopy A Phase I Study of E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia Safety and Effectiveness of Giving Isotretinoin to HIV-Infected Women to Treat Cervical Tumors Costa Rican Natural History Study of HPV and Cervical Neoplasia Measurement of Digital Colposcopy for Fluorescence Spectroscopy of TNC Using a Second Device Effect of Salpingectomy During Conservative Hysterectomy Feasibility of Delphi Screener for Cervical Cytology Study of Topical ABI-1968 in Subjects With Precancerous Cervical Lesions From Human Papillomavirus (HPV) Infection. Study of Topical ABI-1968 in Subjects With Precancerous Cervical Lesions From Human Papillomavirus (HPV) Infection Gene Therapy Follow up for Subjects Previously Enrolled in NCI Experimental Transplantation and Immunology Branch Studies Home-Based or Clinic-Based Human Papillomavirus (HPV) Screening Viral Load Determination and Biomarkers of High Risk Human Papillomavirus (HPV) – Types in HIV-positive Men Immuno-persistence Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls A Bridging Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls TWO DİFFERENT ELECTROSURGERY DEVICES AS MONOPOLAR HOOC AND PLASMAKINETIC BIPOLAR SPATULA EFFECTIVENESS DURING COLPOTOMY Minimally Invasive Benign Hysterectomy HRME in the Screening of Cervical Cancer Precursor Lesions in Brazil (UH3 – Brazil) Diagnostic Imaging Aid for Management of Cervical Lesions Cervical Cancer Early Endpoints and Determinants Triage Strategies in Cervical Cancer Prevention Genotypification and Predisposing Factors in Human Papilloma Virus Infection Development of Immunological Assays for the Evaluation of Tumor Antigen Specific Immunity Chinese Cancer Prevention Study(CHICAPS) The Development of a “Mother/Child, Screen, Treat and Vaccinate Program” in Manchay and Iquitos, Peru HRME: Screening for Cervical Cancer and Its Precursors in Low‐Resource Settings A Trial for Patients With Advanced/Recurrent Cervical Cancer HPV Genotyping by DR. HPV Genotyping in Vitro Diagnostic Device (IVD) Kit in Exfoliated Cells of the Uterine Cervix Human Papillomavirus (HPV) and Risk of Cervical Precancer and Cancer Self-sampling for Non-attenders to Cervical Cancer Screening HPVPro Study: Comparison of HPV Detection in Clinician-collected Cervical Swabs and Self-sampled Cervicovaginal Swabs Acceptability and Efficacy of Self-sampling for Cervical Cancer Screening: A Pilot Study Clinical Trial for the Use of a Novel Cell Collector Device to Retrieve Cells From the Uterine Cervix Human Papillomavirus Epidemiology in Nigeria Impact of HPV Vaccine On The Prevalence Of HPV In Norway Deciphering Mechanisms Underlying Cancer Immunogenicity Expression of Oncogenic Human Papillomavirus E6/E7 Protein in Tampon Self-Tests Spectroscopic Evaluation of Cervical Neoplasia Evaluating the 2-dose Immunization Schedule of Human Papillomavirus (HPV)-16/18 in Adolescent Females Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3) Human Papilloma Virus (HPV) Vaccine Trial in Young Adolescent Women With GlaxoSmithKline Biologicals’ (GSK Bio) HPV-16/18 Vaccine Participation in Screening for Cervical Cancer: Interest of a Self-sampling Device Provided by the General Practitioner Self-sampling and Human Papillomavirus (HPV)-Testing for Unscreened Women in Cervical Cancer Prevention Human Papillomavirus (HPV) Vaccine Consistency and Non-inferiority Trial in Young Adult Women DNA Methylation Biomarkers for Cervical Cancer Screening Evaluation of in Vitro Devices on Self-collected Vaginal Swab and Urine Sample for Testing of Human Papilloma Virus The SAFE Study: Satisfaction and Adherence to Follow-Up With Colposcopy Exams Impact of AV2 Antiviral Drug on the Treatment of HPV-associated Lesions of the Uterine Cervix Can Text Reminders Improve Uptake of Cervical Screening? Comparing Two Techniques of Haemostasis After Cervical Conization A Comparison Study of Two Community Outreach-Based Approaches to Increase Participation of Women Living in the Mississippi Delta in Cervical Cancer Screening FASTER-Tlalpan Study HPV Integration Testing for Human Papillomavirus-Positive Women Randomized Implementation of Primary HPV Testing in the Organized Screening for Cervical Cancer in Stockholm Dose-Ranging Study of Recombinant Human Papillomavirus Virus 16/18 Bivalent Vaccine Cervical Cytology – Do SMS Reminders Increase Participation in the Cervical Screening Programme? Comparison of Pelvic Lymphadenectomy Versus Isolated Sentinel Lymph Node Biopsy Procedure for Early Stages of Cervical Cancers : a Multicenter Study With Evaluation of Medico-economic Impacts The Study of Folate Receptor-Mediated Staining Solution (FRD™) In Cervical Lesion Detection Effectiveness of Cervical Screening in HPV Vaccinated Women Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program Human Papillomavirus (HPV) Testing to Improve Cervical Cancer Screening in the Mississippi Delta Validation of Human Papillomavirus Assays and Collection Devices for Self-samples and Urine Samples Effect of Fee on Attendance in Cervical Cancer Screening Cervix Cytological Screening – Comparison of Tampon Self-Test and the Routine Smear. Study of the Diagnostic Efficacy of “Real Time” Niris 1300e Optical Coherence Tomography (OCT) Imaging System in the Management of Pre-invasive and Invasive Neoplasia of the Uterine Cervix LLETZ Under General Versus Local Anesthesia Buffered Lidocaine for Loop Electrosurgical Excision Procedures (LEEPs) Trial on Safety and Pharmacokinetics of Intravaginal Curcumin IMproved PRactice Outcomes and Value Excellence in Colposcopy Visual Inspection With Acetic Acid Compared to Lugol’s Iodine in HIV-infected Women Phase I, Open-Label Study of the Safety, Tolerability, and Immunogenicity PEK Fusion Protein Vaccine Clinical Evaluation of Polarized Light Assisted Colposcopy Indirect Comparison Topotecan Cervical Carcinoma Meta-analysis of Efficacy of Topotecan Efficacy Study of Diathermy Cone Biopsy for the Treatment of Cervical Intraepithelial Lesion Quality of Life in Thai Women Diagnosed Cervical Cancer at King Chulalongkorn Memorial Hospital Serum IGF-II and Cancer: Can IGF II Levels be Used to Monitor and Screen Patients Specifically for Cervical Cancer A Follow-up Extension Study to Evaluate the Persistence of Immune Response to GSK Biologicals’ HPV Vaccine in Healthy Chinese Female Subjects Who Received Three Doses of the Vaccine in the HPV-058 Study TMTP1-ICG Mapping in Colposcopy-directed Biopsy Hemodynamic Stability of Bupivacaine With and Without Adrenaline for Paracervical Block for Cervical Conization Immediate Treatment vs Colposcopic Follow-up for Biopsy-Proven CIN 1 Diagnosis of Cervical Lesions in Women With Unhealthy Looking Cervix Construct Validity of a Large Loop Excision of the Transformation Zone (LLETZ) Training Model Endocervical Evaluation With the Curette Versus Cytobrush for the Diagnosis of Dysplasia of the Uterine Cervix Randomized Controlled Trial of Human Papillomavirus Testing in Primary Cervical Cancer Screening Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation The HPV Self-test as a Test of Cure in Madagascar REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) A Trial of Two Electrosurgical Conizations: Histopathological Analysis of Excision Margins Cold Knife Conization With and Without Lateral Hemostatic Sutures DC Vaccines Targeting HPV16/18 E6/E7 Protein to Regress CINI/CIN2 A Phase III Study of Human Papillomavirus (HPV)-16/18 Vaccine. Evaluation of Human Papilloma Virus (HPV) Self-testing to Increase Screening Uptake Improving Cervical Cancer Screening Among HIV-Infected Women in India REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) Compass – Randomised Controlled Trial of Primary HPV Testing for Cervical Screening in Australia chemQbiosciences:Manual Liquid Based Cytology A Dose-finding Study of MAL and HAL Photodynamic Therapy of Cervical Premalignant Lesions. Diagnostic and Prognostic Value of p16INK4a Expression in Low Grade Squamous Intraepithelial Lesions of the Cervix. Music Listening to Reduce Pain and Anxiety During LEEP A Comparison of Immediate Treatment of CIN1 With Cryotherapy and 12 Month Cytology Follow up in HIV Seropositive Women Aminolaevulinic Acid Photodynamic Therapy of Cervical Persistent HPV Infection and Cervical Neoplasia HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia The Correlations Between HPV L1-Specific Immunologic Responses in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN) Patients and Their Prognosis Safety and Tolerability of Cidofovir Gel Applied on Cervix Squamous Lesions Lidocaine Spray Compared With Submucosal Injection During LEEP: a Randomized Controlled Trial A Post Marketing Surveillance (PMS) Study to Monitor the Safety of GlaxoSmithKline (GSK) Biologicals’ Human Papillomavirus (HPV) Vaccine in Female Chinese Subjects Comparison of Human Papillomavirus Integrated DNA and Messenger RNA in Cervical Neoplasia Cervical And Self-Sample In Screening Study Randomized Trial of Vaginal Self Sampling for Human Papillomavirus (HPV) Factors Associated With Residual Disease In The Central Cone Trial to Evaluate Single- and Double- Freeze Cryotherapy in the Prevention of Cervical Neoplasia Colposcopy Versus HPV Testing to Identify Persistent Cervical Precancers Optimal Strategy for the Management of ASCUS Cytology in Health Care Services of Medellin, Colombia V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110) Effectiveness of HPV Vaccine in Thai Adult Women Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia Dose-finding Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) to Treat Cervical Neoplasia Artesunate Vaginal Inserts for the Treatment of CIN2/3 A Two-Stage Phase 2 Study Of A-007 Topical Gel in High-Grade Squamous Intraepithelial Lesions (HSIL) Trial23 – A Method Study on Cervical Screening in Women Offered HPV-vaccination as Girls An Innovative Treatment for Cervical Pre Cancer A Study of Amolimogene (ZYC101a) in Patients With High Grade Cervical Intraepithelial Lesions of the Uterine Cervix LLETZ Under Direct Colposcopic Vision The Efficacy of Tachosil® for Prevention of Hemorrhage After Loop Electrosurgical Excisional Procedure (LEEP) Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation LLETZ With Videocolposcopy Versus LLETZ With Binocular Colposcopy Imiquimod Treatment of Residual or Recurrent CIN Lesions: a Study Protocol Colposcopy and Dynamic Spectral Imaging (DSI) Imiquimod Treatment of High-grade CIN Treatment of High-Grade Pre-Neoplastic Cervical Lesions (CIN 2/3) Safety and Efficacy of GX-188E Administered Via EP Plus GX-I7 or Imiquimod. Topical Imiquimod vs. LEEP for Women With Carcinoma In-situ of the Cervix Feasibility of the Management of Severe Cervical Dysplasia in a Single Visit Video Colposcopy in Women With Dysplasia Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS) Imiquimod Treatment of CIN Lesions HPV Integration Testing for Cervical Cancer Screening Hemostatic Procedure After Biopsy of the Cervix HPV-cytology Testing Versus Cytology Testing for the Detection of High Grade CIN An Exploratory Safety and Immunogenicity Study of HPV16+ Immunotherapy VB10.16 in Women With HSIL; CIN 2/3) Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix Prevaccination Study of Cervical Human Papillomavirus Types in Yangtze River Delta Area, China Green Tea Extract in Preventing Cervical Cancer in Patients With Human Papillomavirus and Low-Grade Cervical Intraepithelial Neoplasia An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+ Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of Plasmid DNA Therapeutic Vaccine(GX-188E) Multispectral Digital Colposcope With Probe for Detection of Cervical Intraepithelial Neoplasia A Study of VGX-3100 DNA Vaccine With Electroporation in Patients With Cervical Intraepithelial Neoplasia Grade 2/3 or 3 Fischer Cone Biopsy Excisor Versus Loop Excision Procedure for Conization A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3) Coherence Imaging of the Cervical Epithelium With Scanning a/LCI Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia See and Treat in an Outpatient Setting in Women Above 45 Years With Cervical Dysplasia Factors Predicting Persistence of Oncogenic HPV and Cervical Dysplasia in HIV Infected Kenyan Women Smoking Cessation in Women With Gynecological Conditions Recurrence in High-grade Lesions After Conization Evaluation of Initial High Risk Human Papillomavirus (HR-HPV) Viral Load as Predictive Marker for Cervical Intraepithelial Neoplasia Grade 1 (CIN1) Persistence Management of Cervical Intraepithelial Neoplasia Grade 2 Photodynamic Therapy Using Lutetium Texaphyrin in Treating Patients With Cervical Intraepithelial Neoplasia Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia Aminolaevulinic Acid Photodynamic Therapy for HPV+ Low Grade Cervical Intraepithelial Neoplasia (LSIL;CIN1) An Innovative Treatment for Cervical Precancer (UH3) Evaluating Materials to Educate Patients About Cervical Dysplasia A Efficacy and Safety Study of Composite Gel Containing Black Raspberry Extract in Removing HPV From Patients With Cervical Intraepithelial Neoplasia(CIN) After Cervical Conization Performance, Safety, and Efficacy of a New Cyrotherapy Device for Cervical Dysplasia Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia [Part II] Music and Colposcopy in Women With Cervical Dysplasia. Use of Human Papillomavirus Persistence for Determination of Treatment Efficacy Among Women With Cervical Dysplasia ITIC (Imiquimod Therapy in Cervical Intraepithelial Neoplasia)-Trial A Study of RO5217790 in Participants With High Grade Cervical Intraepithelial Neoplasia (CIN) Associated With High Risk Human Papillomavirus (HR-HPV) Infection Local Hyperthermia for the Treatment of Cervical Intraepithelial Neoplasias Comparison of Cervical CIN II/III Treatment Outcomes With Thermal Ablation Device A Trial to Evaluate the Efficacy and Safety of BLS-ILB-E710c in Patients With Cervical Intraepithelial Neoplasia 2/3 (CIN2/3) A Pilot Study of EM-1421 for the Treatment of Cervical Intraepithelial Neoplasia Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia Dose-finding, Safety Study of Plasmid DNA Therapeutic Vaccine to Treat Cervical Intraepithelial Neoplasia Safety of GX-188E DNA Therapeutic Vaccine Administered by Electroporation to Cervical Intraepithelial Neoplasia Grade 3 Effect of Curcumin in Treatment of Squamous Cervical Intraepithelial Neoplasias (CINs) Study of SOR007 Ointment for Cervical Intraepithelial Neoplasia (CIN) Impact on Disease Relapse of HPV Vaccination in Women Treated With LEEP for Cervical Intraepithelial Neoplasia. HOPE9 Focal Ablation of Cervical Precancer Digital Imaging Aid for Assessment of Cervical Dysplasia Intravaginal Artesunate for the Treatment of HPV+ High Grade Cervical Intraepithelial Neoplasia (CIN2/3) TRICIN: Prospective Study on the Efficacy of Single Topical Trichloroacetic Acid (TCA) 85% in the Treatment of Cervical Intraepithelial Neoplasia (CIN 1/2) Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) of Cervical Intraepithelial Neoplasia (CIN) Grade 1 Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II Testing Use of Condoms on Regression of Cervical Intraepithelial Neoplasia Safety Study to Test the Safety of HspE7 and Poly-ICLC Given in Patients With Cervical Intraepithelial Neoplasia Can Alternative Treatment Have an Impact on Cervical Dysplasia? Forced Versus Spray Coagulation in Women Undergoing LLETZ-conization for Cervical Dysplasia: a Randomized Trial Efficacy and Safety Study of PGA (Poly-gamma Glutamic Acid) for Cervical Intraepithelial Neoplasia Oral Diindolylmethane (DIM) for the Treatment of Cervical Dysplasia A Phase II Single-arm Intervention Trial of Nelfinavir in Patients With Grade 2/3 or 3 Cervical Intraepithelial Neoplasia A Pilot Study to Evaluate Ultrasonic Surgical Aspiration as a Treatment Modality for Cervical Dysplasia Physical Cold Atmospheric Plasma for the Treatment of Cervical Intraepithelial Neoplasia Efficacy and Safety Study of BLS_ILB_E710c for the Fertile Women With Cervical Intraepithelial Neoplasia(CIN3) Cryotherapy vs. LEEP to Treat Cervical Intraepithelial Neoplasia (CIN) 2/3 Among HIV-positive Women An Alternative Treatment for Cervical Intraepithelial Neoplasia Using the Focal Loop Electrosurgical Excision Procedure

Brief Title

DEFLAGYN® Vaginal Gel and Spontaneous Remission and Regression of Unclear Cervical Smears and HPV High-risk Infections

Official Title

DEFLAGYN® Vaginal Gel and Spontaneous Remission and Regression of Unclear Cervical Smears and HPV High-risk Infections

Brief Summary

      Human papillomaviruses (HPV) are the most common sexually transmitted pathogens worldwide and
      in most cases are causally associated with the development of cervical cancer, one of the
      most common cancers in women and one of the leading causes of death in women worldwide.
      Precancerous lesions (dysplasias) or the presence of a high-risk HPV subtype are detected by
      a screening smear test performed by a gynecologist. If precancerous lesions are detected,
      conization (= surgical removal of a cone of tissue from the cervix) is the method of choice
      for removing the diseased tissue. However, if the degree of dysplasia is correspondingly low
      or the smear is unclear, then the guideline-compliant non-surgical treatment provides for a
      wait-and-see approach with PAP and HPV smear control after 6-8 months.

      This "wait-and-see" approach can be complemented by local therapy with an immunostimulant.
      For this purpose, DEFLAGYN® (a vaginal gel containing silica and citric acid) and Aldara®
      (imiquimod, a Toll-Like Re-ceptor 7 antagonist) are available. However, while the latter is
      not approved for the treatment of cervical dysplasia or HPV infection, DEFLAGYN® has CE
      marking and approval as a medical device for treatment in a number of indications, such as
      unclear cervical smears, HPV-induced cervical lesions, p16/Ki-67-positive cervical lesions or
      cervical erosions.

      However, available studies on the efficacy of DEFLAGYN are limited. For example, there is
      only one prospective randomized trial (Major et al, 2021, Arch. Gynecol. Obstet.
      303:501-511), which included 216 women with histologically confirmed CIN 1/2. A 3-month
      intravaginal application of DEFLAGYN® resulted in regression of CIN 1/2 in 72% versus 25% in
      the control arm (no intervention). Side effects of therapy with DEFLAGYN® were not observed
      in this study.

      Due to the frequency of CIN and HPV infections in the female population and due to the high
      medical relevance of a conservative method of treating this disease, further methodologically
      high-quality studies on the efficacy of DEFLAGYN® should be performed.
    

Detailed Description

      1. HPV and dysplasia of the cervix uteri Human papillomaviruses (HPV) are the most common
           sexually transmitted pathogens worldwide. The prevalence in both male and female
           populations is high. Epidemiological estimates suggest that 85-91% of sexually active
           adults acquire at least one genital HPV infection by age 50, with approximately 95% of
           HPV infections being spontaneously eliminated within 2 years in terms of HPV immunologic
           clearance. HPV preferentially infects the epithelial cells of the anogenital area and,
           through incorporation of HPV DNA into the host genome of the basal cells of the squamous
           epithelium of the cervix and subsequent expression of viral components, causes
           dysplastic changes in the cervical epithelium that, if left untreated, can develop into
           invasive carcinoma of the cervix (cervical carcinoma).

           Cervical carcinoma is the fourth most common cancer as well as the fourth leading cause
           of cancer-related death in women worldwide, responsible for 6.6% (570,000) of all new
           cancer cases and 7.5% (311,000) of cancer-related deaths in women in 2018.

           The precursor of squamous cell carcinoma of the uterine cervix (approximately 80% of all
           cervical cancers) is cervical intraepithelial neoplasia (CIN), which has three grades of
           expression (CIN1, CIN 2, and CIN 3). Compared with invasive cervical carcinoma, the
           incidence and prevalence of precancerous lesions of the cervix uteri are much higher. It
           is estimated that approximately 100,00 w0omen in Germany develop high-grade dysplasia
           (CIN2/CIN3) each year.

        2. Therapy Dysplasia of the cervix typically becomes conspicuous during gynecological
           screening examinations. Here, smears are taken from the ectocervix and endocervix and
           assessed cytologically for dysplastic cells and the quality of the smear after
           Papanicolaou staining. HPV infection diagnostics are also performed as part of the
           statutory cervical carcinoma screening (annually or every 3 years) in order to detect
           the presence of HPV high risk infections.

           In case of abnormalities in the cervical smear and/or HPV high risk infection with
           suspicion of cervical dysplasia, presentation to a specialized dysplasia consultation is
           recommended for further clarification of dysplastic changes. During the subsequent
           colposcopic examination, a histological tissue sample ('cervical biopsy') of conspicuous
           areas is taken. The histopathological processing of the tissue samples and the
           colposcopic image of the spread of the changes in the cervix then allow individualized
           therapy planning.

        3. Conization as the standard of surgical treatment If precancerous lesions with the
           potential to develop into an invasive cervical tumor are detected, conization (=
           surgical removal of a cone of tissue from the cervix) is the method of choice for
           removing the diseased tissue. The worldwide standard surgical procedure for conization
           is LLETZ conization (="Large Loop Excision of the Transformation Zone"). In addition to
           the risk of local persistence of precancerous lesions if cervical dysplasia is
           incompletely removed, LLETZ also increases the risk of preterm delivery in subsequent
           pregnancy. This risk increases with increasing volume of removed tissue. To reduce or
           avoid the aforementioned complications, conization should be performed under colposcopic
           vision and as little healthy cervical tissue as possible should be removed.

        4. Non-surgical treatment options Non-surgical methods for the treatment of CIN and/or HPV
           high risk infections are limited. According to the current S3 guideline, in case of CIN
           1 and/or HPV high risk infection, a wait-and-see approach with PAP and HPV smear control
           in 6-8 months is possible. Alternatively, local therapy with an immunostimulant may be
           used. DEFLAGYN® and Aldara® are available for this purpose. Aldara® is imiquimod, a
           Toll-Like Receptor 7 (TLR 7) antagonist, which leads to a local immune response.
           However, Aldara® is not approved for the treatment of CIN or HPV infections. DEFLAGYN®,
           on the other hand, has a CE mark and medical device approval for the treatment of
           unclear cervical smears (ASC-US, ASC-H, LSIL, HSIL or PAP II-p, PAP III-p, PAP IIID1,
           PAP IIID2 or PAP III, PAP IIID) or HPV-induced cervical lesions or p16/Ki-67-positive
           cervical lesions or cervical erosions.

        5. DEFLAGYN® - Mode of action and approval status DEFLAGYN® is a vaginal gel containing
           silica and citric acid, which binds pathogens, inhibits their spread and exerts an
           antioxidant effect. It is applied intravaginally and used for 3 months. In a prospective
           randomized study of 216 women with histologically confirmed CIN 1/2, 3 months of
           intravaginal application of DEFLAGYN® resulted in regression of CIN 1/2 in 72% versus
           25% in the control arm (no intervention). The rate of HPV high risk infections decreased
           from 87% to 44% in the intervention arm. No other intervention studies on the efficacy
           of DEFLAGYN® can be found in the literature (PubMed search on 08/14/2022; search terms:
           dysplasia, deflagyn, HPV, silicon dioxide gel, randomized). Side effects of therapy with
           DEFLAGYN® were not observed in the study. Due to the frequency of CIN and HPV infections
           in the female population and due to the high medical relevance of a conservative method
           of this disease, further methodologically high-quality studies on the efficacy of
           DEFLAGYN® are useful.
    


Study Type

Interventional


Primary Outcome

Rate of hr-HPV-positive cervical smears

Secondary Outcome

 Rate of hr-HPV-positive cervical smears

Condition

Cervix Dysplasia

Intervention

DEFLAGYN vaginal gel

Study Arms / Comparison Groups

 Control Arm
Description:  Wait-and-see approach.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

168

Start Date

October 2022

Completion Date

October 2024

Primary Completion Date

April 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Written consent

          -  Unclear cervical smear (ASC-US, ASC-H, LSIL, HSIL or PAP II-p, PAP III-p, PAP IIID1,
             PAP IIID2 (Munich III) or PAP III, PAP IIID, PAP I + HPV high-risk infection)

        Exclusion Criteria:

          -  Pregnancy

          -  Known hypersensitivity to any of the ingredients of the vaginal gel

          -  Insufficient knowledge of the German language

          -  Pre-existing oncological diseases
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clemens B Tempfer, MD, MBA, +49 2323 499, [email protected]

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT05509413

Organization ID

HPV-VG1


Responsible Party

Principal Investigator

Study Sponsor

Ruhr University of Bochum


Study Sponsor

Clemens B Tempfer, MD, MBA, Principal Investigator, Ruhr-Universität Bochum, Marien Hospital Herne


Verification Date

August 2022