Phase IIb/III Parallel-arm, Random., Active-controlled, Double-blind, Double-dummy, Multicenter, Non-inferiority Study in Patients With RVVC to Compare Efficacy, Safety and Tolerability of Topically Administered ProF-001 to Oral Fluconazole
Overview
- Phase
- Phase 2
- Intervention
- Prof-001
- Conditions
- Recurrent Vulvovaginal Candidiasis
- Sponsor
- ProFem GmbH
- Enrollment
- 432
- Locations
- 29
- Primary Endpoint
- Percentage of patients with at least one episode of clinical relapse of VVC during the 12 months study period.
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective, randomized, multi-center, active-controlled, double-blind, double-dummy, multicenter, non-inferiority study comparing the clinical efficacy, safety and tolerability of ProF-001 to fluconazole.
Detailed Description
Eligible subjects will be randomized in a 1:1 ratio to receive either ProF-001 or fluconazole for the treatment of RVVC. Patients diagnosed with RVVC will be randomized to either ProF-001 or fluconazole treatment. Treatment schedule will start with an induction period of 10 (+4) days followed by a six months maintenance period and a subsequent 6 months follow-up (observation) period after end of active treatment. Any episode of VVC grade \> = 3 and positive vaginal smear (native or KOH) with budding yeasts, pseudohyphae or hyphae from test of cure (TOC) visit onwards will be considered as relapse of VVC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients ≥ 18 years
- •Patients suffering from an acute episode in RVVC, characterized by:
- •Positive vaginal smear (native or KOH) for budding yeasts and/or (pseudo-) hyphae, normal or intermediate flora
- •Two or more of the following signs and symptoms of VVC that are characterized as moderate or severe: itching, burning, irritation, edema, redness, or excoriation/fissure (Table 2).
- •At least 3 previous episodes of VVC during the last 12 months (i.e. at least 4 episodes including the current episode)
- •Readiness for sexual abstinence from start of treatment until test of cure (TOC) - visit
- •Ability to understand trial instructions and rating scales as well as ability to comply with treatment
- •Written informed consent
Exclusion Criteria
- •Known hypersensitivity to clotrimazole, diclofenac, fluconazole or any other ingredient of the investigational medicinal product
- •Pregnancy or breast feeding at time of screening (for all females of childbearing potential, negative pregnancy test at screening and monthly during active treatment period will be performed). Females in childbearing potential must use adequate contraception during the active treatment period (sexual abstinence is an accepted method of birth control)
- •Menstrual bleeding (spotting is not an exclusion criterion) during the first three days of treatment during the induction period
- •Acute cystitis diagnosed by anamnesis and urinary dip stick (positive for leukocytes and nitrites) during screening examination
- •Patients with other infectious causes of vulvovaginitis assessed during gynecological examination at screening (e.g., bacterial vaginosis, Trichomonas vaginalis, Herpes simplex)
- •Patients with other clinical gynecological abnormalities, such as infections of the upper urogenital tract (pelvic inflammatory disease, adnexitis) or known high-grade cervical dysplasia at screening
- •Subjects with another vaginal or vulvar condition that would confound the interpretation of clinical response (e.g. lichen sclerosus, neuropathic pain, herpes zoster)
- •Treatment with antimycotics (systemic or vaginal) within the prior 3 days of randomization or during study period other than IMP (investigational medicinal product)
- •Chronic (daily) use of non-steroidal anti-inflammatory medication during induction and maintenance period (\>4 weeks)
- •Vaginal or oral antibiotic treatment during induction period
Arms & Interventions
ProF-001 Group
ProF-001 Group: • During induction period: app. 5 g of ProF-001 for 6 days (twice daily app. 2.5 g vulvar/ intravaginal application of cream), followed by 4 days of app. 2.5 g of ProF-001 at bedtime and 1 placebo capsule on days 1, 4, and 7 and • During maintenance period: 2 doses of app. 2.5 g of ProF-001 per week for 22 weeks (total of 44 single doses) and 1 placebo capsule per week for 24 weeks
Intervention: Prof-001
ProF-001 Group
ProF-001 Group: • During induction period: app. 5 g of ProF-001 for 6 days (twice daily app. 2.5 g vulvar/ intravaginal application of cream), followed by 4 days of app. 2.5 g of ProF-001 at bedtime and 1 placebo capsule on days 1, 4, and 7 and • During maintenance period: 2 doses of app. 2.5 g of ProF-001 per week for 22 weeks (total of 44 single doses) and 1 placebo capsule per week for 24 weeks
Intervention: Placebo capsule
Fluconazole Group
Fluconazole Group: * During induction period: 1 Fluconazole 150 mg capsule on days 1, 4, and 7 and a daily dose of app. 5 g of placebo cream for 6 days (twice daily 2.5 g vulvar/ intravaginal application of cream), followed by 4 days of 2.5 g of placebo cream at bedtime and * During maintenance period: 1. capsule of fluconazole 150 mg per week for 24 weeks and two doses of 2.5 g of placebo cream per week for 22 weeks (total of 44 single doses)
Intervention: Fluconazole 150 mg
Fluconazole Group
Fluconazole Group: * During induction period: 1 Fluconazole 150 mg capsule on days 1, 4, and 7 and a daily dose of app. 5 g of placebo cream for 6 days (twice daily 2.5 g vulvar/ intravaginal application of cream), followed by 4 days of 2.5 g of placebo cream at bedtime and * During maintenance period: 1. capsule of fluconazole 150 mg per week for 24 weeks and two doses of 2.5 g of placebo cream per week for 22 weeks (total of 44 single doses)
Intervention: Placebo cream
Outcomes
Primary Outcomes
Percentage of patients with at least one episode of clinical relapse of VVC during the 12 months study period.
Time Frame: after 12 months
Registration of the number of patients with a clinical relapse within 12 months after randomization, clinical relapse of VVC is defined as severity score of VVC grade ≥ 3 with positive vaginal smear (native or KOH) with budding yeast or hyphae)
Secondary Outcomes
- Proportion of patients with clinical cure (absence of signs and symptoms of VVC) at 6, 8, 10 and 12 months after randomization(6, 8, 10, 12 months)
- Percentage of patients with clinical cure (defined as absence of signs and symptoms of VVC) at the test of cure visit, day 10 (+ 4 days)(after 2 weeks)
- Patient reported outcome of time to termination of clinical symptoms using the 11-point numeric rating scale (NRS) for burning, itching, soreness/irritation(within 2 weeks after randomization)
- Symptom relief reported by patients within the first 6 to 12 hours and following day after first application. Symptom relief as improvement of ≥ 2 points of symptoms compared to pre-treatment in the NRS.(48 hours)