Clinical trial NCT02687789: Safety, Tolerability and Efficacy of Vaginal Suppository WO3191 in the Post-treatment of Bacterial Vaginosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vaginosis, Bacterial
Keywords: Bacterial Vaginosis
BV
Lead sponsor: Dr. August Wolff GmbH & Co. KG Arzneimittel
Sponsor class: INDUSTRY
Collaborators: name: PHARMALOG Institute for Clinical Research
name: Bremer Pharmacovigilance Service GmbH
First posted: 2016-02-22
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Local tolerability of IMD defined as a cumulative sum score of solicited local ADE for each Patient
timeFrame: 3 weeks
Secondary outcomes:
measure: Subjective symptoms (local tolerability)
timeFrame: 3 weeks
measure: Objective findings
timeFrame: 3 weeks
measure: Global judgement of tolerability
timeFrame: 3 weeks
measure: AE and ADE (Safety)
timeFrame: up to 4 months
measure: Occurrence of AE / SAE / ADE / SADE (Serious Adverse Event) (Safety)
timeFrame: up to 4 months
measure: Characteristics of AE / SAE / ADE / SADE (Safety)
timeFrame: up to 4 months
measure: Change in biofilm EPS
timeFrame: up to 4 months
measure: Change in pH-value from vaginal smear
timeFrame: within 4 months
measure: Change in Nugent-Score
timeFrame: within 3 weeks
measure: Change in Vaginal flora
timeFrame: within 4 months
measure: Time to recurrence of BV
timeFrame: up to 3 months
Other outcomes:
measure: Global judgement of the IMD
timeFrame: 3 weeks
Locations:
city: Aachen
country: Germany
facility: Dr. Gerick
city: Betzdorf
country: Germany
facility: Dr. Hofmann
city: Bielefeld
country: Germany
facility: Dr. de Brabandt
city: Frankfurt
country: Germany
facility: Dr. Werner Göttker-Schnetmann
city: Munich
country: Germany
facility: Dr. Deininger
city: Munich
country: Germany
facility: Dr. Kränzlin
city: Munich
country: Germany
facility: Dr. Kästner
city: Munich
country: Germany
facility: Dr. Kühne
city: Siegen
country: Germany
facility: Bianca Moll-Bosch
city: Steinhagen
country: Germany
facility: Dr. Susanne Feidicker
city: Weilburg
country: Germany
facility: Thomas Riepen
city: Wuppertal
country: Germany
facility: Dr. Waldschütz
city: Wuppertal
country: Germany
facility: Prof. Mendling
Study officials:
affiliation: Dr. August Wolff GmbH & Co. KG Arzneimittel
name: Prof. Christoph Abels, MD
role: STUDY_DIRECTOR
affiliation: St. Anna Klinik, Wuppertal
name: Prof. Werner Mendling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gottschick C, Deng ZL, Vital M, Masur C, Abels C, Pieper DH, Rohde M, Mendling W, Wagner-Dobler I. Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessary-clinical study and microbiota analysis. Microbiome. 2017 Sep 13;5(1):119. doi: 10.1186/s40168-017-0326-y.
citation: Gottschick C, Deng ZL, Vital M, Masur C, Abels C, Pieper DH, Wagner-Dobler I. The urinary microbiota of men and women and its changes in women during bacterial vaginosis and antibiotic treatment. Microbiome. 2017 Aug 14;5(1):99. doi: 10.1186/s40168-017-0305-3.