A Phase IIb/III Study of Prof-001 for the Treatment of Patients With Recurrent Vulvovaginal Candidiasis (RVVC)

NCT04734405 | Unknown Phase 2

• 1 other identifier: ProF-001 IIb-III
• Study Type: interventional
• Target: 432
• Locations: 3 countries
• Sites: 29

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.

Conditions

Recurrent Vulvovaginal Candidiasis

Keywords

Recurrent VVC; RVVC; Vulvovaginal candidiasis; ProF-001; Fluconazole; Vulvovaginitis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with at least one episode of clinical relapse of VVC during the 12 months study period.

  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)

  after 12 months

Secondary Outcomes (4)

• 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

Other Outcomes (2)

• Improvement of patient reported health related quality of life score at the end of the observation period using the EQ-5D questionnaire

  0, 6 and12 months

• Sexual function related to pain and improvement thereof (see Annex I)

  0, 6 and12 months

Study Arms (2)

ProF-001 Group

EXPERIMENTAL

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

Drug: Prof-001; Drug: Placebo capsule

Fluconazole Group

ACTIVE COMPARATOR

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)

Drug: Fluconazole 150 mg; Drug: Placebo cream

Interventions

Prof-001 DRUG

Prof-001 cream

ProF-001 Group

Fluconazole 150 mg DRUG

Fluconazole capsule

Fluconazole Group

Placebo cream DRUG

ointment base to mimic Prof-001

Fluconazole Group

Placebo capsule DRUG

encapsulated lactose powder to mimic 150 mg fluconazole capsule

ProF-001 Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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
• Vaginal use of corticosteroids, chronic systemic (oral, rectal or intravenous) use of corticosteroids during treatment and follow-up period (≥ 5 mg oral prednisolone/d or equivalent dose \> 4 weeks). Topical dermal (except vulvar), intranasal or inhalative corticosteroids for allergy, asthma or chronic obstructive pulmonary disease allowed.
• Vaginal use of antihistaminic drugs during induction period
• Patients receiving anti-estrogen treatment for breast cancer, patients receiving immunosuppressive drugs
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption."
• Active malignancy (except non-melanoma skin cancer, or carcinoma in situ of cervix) or current treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, hormone therapy for cancer treatment, targeted therapy or gene therapy)
• Known major uncontrolled medical disorder(s) that renders the subject unsuitable for participation in the study, including but not limited to: comorbid condition with an estimated life expectancy of ≤ 12 months, known acquired immune deficiency syndrome, patients with chronic kidney disease on dialysis, patients with severe pulmonary (requiring home oxygen, uncontrolled COPD (chronic obstructive pulmonary disease) Gold III/ IV) or cardiovascular conditions (heart failure NYHA IV)

Sponsors & Collaborators

• ProFem GmbH: lead
• Montavit Ges.m.b.H.: collaborator

Study Sites (29)

Ordination Dr. Nehoda

Innsbruck, Tyrol, 6020, Austria

Location

Ordination Dr. Peter Brock

Innsbruck, Tyrol, 6020, Austria

Location

Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK

Innsbruck, Tyrol, 6020, Austria

Location

Ordination Dr. Mayr

Kufstein, Tyrol, 6330, Austria

Location

Ordination Dr. Fischer

Bregenz, Vorarlberg, 6900, Austria

Location

Universitätsklinik für Frauenheilkunde, AKH

Vienna, 1090, Austria

Location

Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen

Vienna, 1210, Austria

Location

Provita Sp. z o.o. Fabryczna 13 D

Katowice, 40-611, Poland

Location

CMR

Katowice, 40-628, Poland

Location

Centrum Zdrowia Kobiety Komed,

Kielce, 25-435, Poland

Location

Komed

Kielce, 25-435, Poland

Location

PZS Oleśnica

Oleśnica, 56-400, Poland

Location

Fem-Med

Poznan, 60-512, Poland

Location

Gaja Poradnie Lekarskie

Poznan, 61-251, Poland

Location

Bonus 2001 Sp. z o.o. Sp. K.

Skórzewo, 60-185, Poland

Location

Gabinety Lekarskie SIGNUM

Skórzewo, 60-185, Poland

Location

DC-MED., Dworcowa 5

Swidnica, 58-100, Poland

Location

Astimed Sp. z o.o.,

Warsaw, 01-875, Poland

Location

Centrum medyczne Lux MED

Warsaw, 02-672, Poland

Location

Centrum Medyczne LUX MED Swidnicka 40

Wroclaw, 50-024, Poland

Location

BESME s.r.o

Bánovce nad Bebravou, Slovakia

Location

MILLY s.r.o.

Bratislava, Slovakia

Location

Gynedur s.r.o.

Dubnica nad Váhom, Slovakia

Location

MCM GYNPED s.r.o.

Dubnica nad Váhom, Slovakia

Location

Gyncentrum Nitra s.r.o.

Nitra, Slovakia

Location

GYNAMA s.r.o.

Nové Mesto nad Váhom, Slovakia

Location

BrenCare s.r.o

Poprad, Slovakia

Location

GYNECARE s.r.o.

Púchov, Slovakia

Location

Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia

Trenčín, Slovakia

Location

MeSH Terms

Conditions

Candidiasis, Vulvovaginal; Vulvovaginitis

Interventions

Fluconazole

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vulvitis; Vulvar Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Herbert Kiss, Prof.

  Universitätsklinik für Frauenheilkunde

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel-arm, Randomized, Active-controlled, Double-blind, Double-dummy

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: February 2, 2021
• Study Start: October 1, 2019
• Primary Completion: November 1, 2022
• Study Completion: December 30, 2022
• Last Updated: September 22, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (7); PL (13); SL (9)