Safety, Tolerability and Efficacy of Vaginal Suppository WO3191 in the Post-treatment of Bacterial Vaginosis

Vaginosis, Bacterial Clinical Trial

Official title:

A Prospective Parallel-design, Double-blind, Randomised, Controlled Investigation to Gain Clinical Experience and Further Knowledge About the Certified Medical Device Vaginal Suppository WO 3191 With Respect to Safety, Tolerability and Efficacy in the Post-Treatment of Bacterial Vaginosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02687789
• Other study ID #: WOAF-11/2012
• Secondary ID: CIV-113-12-01173
• Status: Completed
• Phase: N/A
• First received: October 12, 2015
• Last updated: February 16, 2016
• Start date: April 2014
• Est. completion date: September 2015

Study information

• Verified date: February 2016
• Source: Dr. August Wolff GmbH & Co. KG Arzneimittel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Bacterial Vaginosis (BV) is a common infectious disorder and is characterized by a disturbance in the vaginal microbiological milieu. Anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae overgrow the physiologic vaginal flora which is dominated by Lactobacilli. BV can arise and remit spontaneously but often presents as a recurrent disease.

New findings indicate that the presence of an adherent bacterial biofilm on the vaginal mucosa seems to be the reason for the recurrence of BV as well as the overgrowth condition by anaerobic bacteria. Biofilms are defined as a structured consortium of bacteria embedded in a matrix of extracellular polymeric substances (EPS).

The purpose of this study is to achieve substantial results with respect to tolerability and safety, and to gain further knowledge on the clinical efficacy of Vaginal suppository WO3191, the investigation will be performed in a parallel-design, double-blind, randomised, controlled manner.

Description:

This investigation is a multicentre, parallel-group, double-blind, controlled trial with an open Follow-up Phase of 12 weeks. It is conducted to gain clinical experience and further knowledge about the certified medical device Vaginal suppository WO3191 in women with bacterial vaginosis.

In this investigation the Investigational Medical Device (IMD) will be used as post-treatment following standard therapy with oral metronidazole for BV. IMD will be applied 2 times a week for 3 weeks.

The primary purpose is the evaluation of the safety and local tolerability of WO3191, therefore all adverse events (AEs) and adverse device effects (ADEs) will be documented. Furthermore, patients will be asked for possibly arising subjective vaginal symptoms (burning, itching, bleeding, pain, dryness) and will be examined for possibly arising objective vaginal findings (redness, petechial bleeding, dryness, swelling).

The secondary purpose of this investigation is to gain clinical experience and further knowledge about Vaginal suppository WO3191 with respect to the efficacy in the post-treatment of bacterial vaginosis.

In addition pH-values and microbiological data shall be examined.

Furthermore, the difference between Vaginal suppository WO3191 (Group A) and the comparator (Vagisan® Lactic Acid, group B) with respect to the safety, tolerability and the efficacy in the post-treatment of bacterial vaginosis shall be evaluated exploratively.

Patients who have completed all regular visits (Visit 1 - 4; Visit 1 - Screening, Visit 2 - Randomization, Start of application of IMD; Visit 3 - one week after Visit 2; Visit 4 - two weeks after Visit 3, End of application of IMD) of the investigation shall attend an observational Follow-up Phase of 12 weeks with a final Visit 5. At Visit 5 recurrences of BV as well as the sustainability of the efficacy of Vaginal suppository WO3191 will be evaluated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: September 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Signed declaration of consent and signed data protection declaration after having been informed about the nature, relevance and the scope of the investigation and about the expected desired and undesired effects of the IMD

• Premenopause, age 18 to 50 years (incl. patients with Intrauterine device, e.g. Mirena® with amenorrhoea)

• Acute BV (at least 3 of 4 Amsel's Criteria fulfilled and Nugent Score > 6)

• Existing bacterial biofilm in the vagina, verified by positive EPS of bacterial biofilm and by microscopy

• Requirement of oral treatment of metronidazole for BV

Exclusion Criteria:

• Postmenopause (no menses in the last six months prior to enrolment)

• Positive Herpes simplex infection

• Positive Candida spp. infection

• Positive Trichomonas spp. infection

• Pathologic PAP (III, III D-V) within the last 3 months

• Chronic immunosuppressive diseases (i.e. HIV) or treatment (i.e. transplantation)

• Malignant conditions of CIN, VIN or VAIN, currently and / or within the past 6 months

• Presence or history (within the last 5 years) of any other malignancy

• Previous chemotherapy (within 6 months before start of this investigation)

• Current vaginal or systemic treatment with antibiotics or corticosteroids, systemic treatment with NSAIDs (nonsteroidal anti-inflammatory drugs) within the last two weeks prior to start of this investigation (except metronidazole for the treatment of BV: prescription of metronidazole before investigation entry; except NSAIDs taken in a single dose in case of need, e.g. for headache)

• Use of not permitted contraception or not willing to use contraception (Allowed contraception: oral hormonal contraceptives, intrauterine device, surgical, sexual abstinence; Not permitted contraception: condoms, local spermicides, intravaginal contraceptive measures)

• Pregnancy or lactation

• Active Smokers (more than 5 cigarettes per day)

• Use of any other intravaginal medicinal product or medical device (including all intravaginal contraceptive measures (e.g. NuvaRing®, local spermicides)

• Known hypersensitivity to one or more of the active and / or inactive ingredients of the antibiotic treatment (metronidazole: mandatory for inclusion)

• Known hypersensitivity to one or more of the ingredients of the IMD (test product and/or comparator)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Other:
• Medical Device: WO3191
application of vaginal suppository WO3191: 2 days per week (with a treatment-free interval of three days or two days, respectively; e.g. Monday and Friday)
• Medical Device: Vagisan® Lactic Acid
application of Vagisan® Lactic Acid: 2 days per week (with a treatment-free interval of three days or two days, respectively; e.g. Monday and Friday)

Locations

Country	Name	City	State
Germany	Dr. Gerick	Aachen
Germany	Dr. Hofmann	Betzdorf
Germany	Dr. de Brabandt	Bielefeld
Germany	Dr. Werner Göttker-Schnetmann	Frankfurt
Germany	Dr. Deininger	Munich
Germany	Dr. Kästner	Munich
Germany	Dr. Kränzlin	Munich
Germany	Dr. Kühne	Munich
Germany	Bianca Moll-Bosch	Siegen
Germany	Dr. Susanne Feidicker	Steinhagen
Germany	Thomas Riepen	Weilburg
Germany	Dr. Waldschütz	Wuppertal
Germany	Prof. Mendling	Wuppertal

Sponsors (3)

Lead Sponsor	Collaborator
Dr. August Wolff GmbH & Co. KG Arzneimittel	Bremer Pharmacovigilance Service GmbH, PHARMALOG Institute for Clinical Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Global judgement of the IMD	Global judgement of the IMD by investigator and patient	3 weeks	No
Primary	Local tolerability of IMD defined as a cumulative sum score of solicited local ADE for each Patient	Local tolerability of the IMD will be defined as a cumulative sum score of the solicited local (vaginal) ADE (consisting of subjectively experienced symptoms rated by the patient: burning, itching, bleeding, pain, dryness and objectively documented findings rated by the physician: redness, petechial bleeding, dryness, swelling) for each patient after 1 and 3 weeks of application (Visit 3 and Visit 4, respectively).	3 weeks	No
Secondary	Subjective symptoms (local tolerability)	Each of the subjective symptoms (scored from 0 [none/normal] to 3 [severe]) at Visit 2 (before the first application), Visit 3 (after 1 week of application) and Visit 4 (after 3 weeks of application)	3 weeks	No
Secondary	Objective findings	Each finding (scored from 0 [none/normal] to 3 [severe]) as well as each sum score at Visit 3 (after 1 week of application) and Visit 4 (after 3 weeks of application) will be summarised by the maximum value and the mean value for Visit 3 and Visit 4, respectively	3 weeks	No
Secondary	Global judgement of tolerability	Global judgement of tolerability by investigator and patient at Visit 4 (after 3 weeks of application)	3 weeks	Yes
Secondary	AE and ADE (Safety)	Unsolicited AEs and ADEs	up to 4 months	Yes
Secondary	Occurrence of AE / SAE / ADE / SADE (Serious Adverse Event) (Safety)	Occurrence of AE / SAE / ADE / SADE	up to 4 months	Yes
Secondary	Characteristics of AE / SAE / ADE / SADE (Safety)	Characteristics of occured AE / SAE / ADE / SADE	up to 4 months	Yes
Secondary	Change in biofilm EPS	Proof of the biofilm EPS at Visit 2 (before the first application), Visit 3 (after 1 week of application), Visit 4 (after 3 weeks of application) and Visit 5 (after Follow-up Phase, i.e.12 weeks after the end of the application Phase (Visit 4)); Combined Parameter: Evaluation of Extracellular Polymeric Substances (EPS) in urine samples and evaluation of existence of bacterial biofilm	up to 4 months	No
Secondary	Change in pH-value from vaginal smear	pH-value from vaginal smear at visit 2 (before the first application), Visit 3 (after 1 week of application), Visit 4 (after 3 weeks of application) and Visit 5 (after Follow-up Phase, i.e.12 weeks after the end of the application Phase (Visit 4))	within 4 months	No
Secondary	Change in Nugent-Score	Nugent-Score at Visit 2 (before the first application), Visit 3 (after 1 week of application) and Visit 4 (after 3 weeks of application)	within 3 weeks	No
Secondary	Change in Vaginal flora	Vaginal flora (Lactobacillus spp., Atopobium vaginae and Gardnerella vaginalis) at Visit 2 (before the first application), Visit 3 (after 1 week of application) Visit 4 (after 3 weeks of application) and Visit 5 (after Follow-up Phase, i.e.12 weeks after the end of the application Phase (Visit 4))	within 4 months	No
Secondary	Time to recurrence of BV	Time from the end of application (Visit 4) to the first recurrence of BV within the Follow-up Phase of 12 weeks	up to 3 months	No