Clinical trial NCT03115073: ProF-001_Phase IIa
Official title: A Phase IIa Randomized, Active-controlled, Double-blind, Dose-escalation Study in Patients With Vulvovaginal Candidiasis to Evaluate Dose Response Relationship of Clinical Efficacy, Safety and Tolerability of Topically Administered ProF-001
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Vulvovaginal Candidiasis (VVC)
Keywords: Vulvovaginal candidiasis
Candiplus
Clotrimazole
Safety
Tolerability
Clinical efficacy
Lead sponsor: ProFem GmbH
Sponsor class: INDUSTRY
First posted: 2017-04-14
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, prospective, active-controlled, double-blind, dose-escalation study comparing dose response of clinical efficacy, safety, local tolerability of three different doses of ProF-001/Candiplus® (Candiplus® 0.2%, Candiplus® with 0.3%, Candiplus® with 0.4%) to 1% clotrimazole vaginal cream.

Patients with acute episode of vulvovaginal candidiasis (VVC) will be randomized to receive a daily dose of either 5 ml (intravaginal) of Candiplus® at three different doses for the first 3 days and 2.5 ml for the remaining 3 days or 5 ml (intravaginal) application of 1% clotrimazole cream over the first 3 days and 2.5 ml for the remaining 3 days according to the following scheme (with each application 2 cm of cream will be applied to the vulvar region):

Cohort 1: Candiplus® 0.2% versus clotrimazole mono Cohort 2: Candiplus® 0.3% versus clotrimazole mono Cohort 3: Candiplus® 0.4% versus clotrimazole mono Randomization into the cohorts will occur consecutively from the lowest dose to the highest dose, i.e. patients will be randomized first in cohort 1 and finally in cohort 3.

The proposed study is - after a pilot study to assess critical pharmacokinetic data - the second study within a clinical trial program with the objective to develop a new combination therapy for the treatment of vulvovaginal candidiasis.

The new combination consists of two registered drug substances.


Eligibility criteria: Inclusion Criteria:

* Premenopausal female patients ≥ 18 years old
* Patients suffering from an acute episode of vulvovaginal candidiasis, characterized by:

  * Positive vaginal smear (native, KOH) for budding yeasts and/or fungal (pseudo-) hyphae, normal or intermediate flora (G I and G II)
  * Positive clinical symptoms (itching, burning, irritation, edema, erythema, excoriations), with a subjective symptom score of at least 3 (0=absent, 1=mild, 2=moderate, and 3=severe), with score being at least moderate for at least 1 subjective symptom and itching being present, and a total sign and symptom score of at least 4
* Readiness for sexual abstinence from start of treatment until test of cure (TOC) - visit
* Sufficient knowledge of German language to understand trial instructions and rating scales, and ability to comply with treatment
* Written informed consent prior to enrolment

Exclusion Criteria:

* Known hypersensitivity to any ingredient of the investigational medicinal product
* Pregnancy or breast feeding at time of screening
* Menstrual bleeding (spotting is not an exclusion criterion) during the first three days of treatment
* Acute cystitis
* Patients with clinical signs of other infectious causes of vulvovaginitis: bacterial vaginosis (GIII), trichomonas vaginalis, herpes simplex genitalis
* Treatment with antimycotics (systemic or vaginal) within 7 days of randomization
* Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs)
* Patients with other clinical gynecological abnormalities, such as infections of the upper urogenital tract (pelvic inflammatory disease, adnexitis)
* Subjects with another vaginal or vulvar condition that would confound the interpretation of clinical response (e.g. Lichen sclerosus, neuropathic pain)
* Subjects who will be under treatment or surgery for gynecological pathologies during the study period, i.e, cervical intraepithelial neoplasia, cervical carcinoma, other neoplasms
* Known alcohol, drug or medication abuse
* Any clinically relevant concomitant condition that could compromise the objectives of this study and/ or the patient's compliance (eg. known immune deficiency syndrome with clinical relevance at time of screening)
* Participation in another interventional clinical trial within the last 30 days
* Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor

Primary outcomes:
measure: Combined outcome measure of: Symptom relief within the first 60 minutes (after application of investigational product or active control) and clinical cure at day 7 (± 3 days).
timeFrame: within 60 minutes after application and at day 7 (± 3 days) after drug application
Secondary outcomes:
measure: Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication
timeFrame: overall study period (max. 65 days)
measure: Symptom relief within the first 60 minutes (after application of investigational product or active control, reduction of the subjective symptom score ≥ 2)
timeFrame: within 60 minutes after drug application
measure: Clinical cure (absence of signs and symptoms of VVC) at the TOC visit (=day 7/ accepted time window ±3days)
timeFrame: day 7 ±3 days after drug application
measure: Mycological outcome: Vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
timeFrame: day 7 ±3 days after drug application
measure: Responder outcome: absence of signs and symptoms plus vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days)
timeFrame: day 7 ±3 days after drug application
measure: Time to improvement of symptoms after first intervention
timeFrame: overall study period (max. 65 days)
measure: Time to termination of clinical symptoms
timeFrame: overall study period (max. 65 days)
measure: Clinical relapse of VVC during follow-up period
timeFrame: follow-up period (from day 8 to day 60)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Schwaz
country: Austria
facility: Bezirkskrankenhaus Schwaz
city: Vienna
country: Austria
facility: Medical University Vienna
Study officials:
affiliation: Medical University of Vienna
name: Herbert Kiss, Ao.Univ.Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
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