ProF-001_Phase IIa

Sponsor

ProFem GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT03115073

Collaborator

(none)

Enrollment

Locations

Arms

15.8

Actual Duration (Months)

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Candidiasis (VVC)	Drug: Candiplus Drug: Clotrimazole	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 4, 2017

Actual Primary Completion Date :

Jul 30, 2018

Actual Study Completion Date :

Jul 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0,2% Candiplus Candiplus® 0.2%	Drug: Candiplus Administration of Candiplus
Experimental: 0,3% Candiplus Candiplus® 0.3%	Drug: Candiplus Administration of Candiplus
Experimental: 0,4% Candiplus Candiplus® 0.4%	Drug: Candiplus Administration of Candiplus
Active Comparator: Clotri mono Clotrimazole mono	Drug: Clotrimazole Administration of Clotrimazole

Outcome Measures

Primary Outcome Measures

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). [within 60 minutes after application and at day 7 (± 3 days) after drug application]
As the primary outcome symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected. Furthermore clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.

Secondary Outcome Measures

Number of patients with local adverse events and serious adverse events (SAEs) with causal relationship to study medication [overall study period (max. 65 days)]
All local adverse events and serious adverse events with causal relationship to study medication (drug reaction) will be documented in a descriptive manner.
Symptom relief within the first 60 minutes (after application of investigational product or active control, reduction of the subjective symptom score ≥ 2) [within 60 minutes after drug application]
Symptom relief within the first 60 minutes will be documented. A reduction of the subjective symptom score ≥ 2 is expected.
Clinical cure (absence of signs and symptoms of VVC) at the TOC visit (=day 7/ accepted time window ±3days) [day 7 ±3 days after drug application]
Clinical cure at day 7 will be documented. Clinical cure is defined as absence of signs and symptoms of VVC.
Mycological outcome: Vaginal swab culture negative for growth of Candida albicans and/or Candida species at the TOC visit (day 7 / ±3days) [day 7 ±3 days after drug application]
A vaginal swab culture will be taken on day 7 / ±3days. The test result is expected to be negative for growth of Candida albicans and/or Candida species.visit (day 7 / ±3days)
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) [day 7 ±3 days after drug application]
Presence or absence of signs and symptoms will be documented. Vaginal swab culture is expected to be negative for growth of Candida albicans and/or Candida species at the TOC visit.
Time to improvement of symptoms after first intervention [overall study period (max. 65 days)]
The time to improvement of symptoms after the first intervention will be documented.
Time to termination of clinical symptoms [overall study period (max. 65 days)]
The time to termination of clinical symptoms will be documented.
Clinical relapse of VVC during follow-up period [follow-up period (from day 8 to day 60)]
Every clinical relapse of VVC during the follow-up period will be documented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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