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

Recurrent Vulvovaginal Candidiasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04734405
• Other study ID #: ProF-001 IIb-III
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2019
• Est. completion date: December 30, 2022

Study information

• Verified date: September 2022
• Source: ProFem GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 432
• Est. completion date: December 30, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

• 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)

• 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

Related Conditions & MeSH terms

• Candidiasis
• Candidiasis, Vulvovaginal
• Recurrence
• Recurrent Vulvovaginal Candidiasis

Intervention

Drug:
• Prof-001
Prof-001 cream
• Fluconazole 150 mg
Fluconazole capsule
• Placebo cream
ointment base to mimic Prof-001
• Placebo capsule
encapsulated lactose powder to mimic 150 mg fluconazole capsule

Locations

Country	Name	City	State
Austria	Ordination Dr. Fischer	Bregenz	Vorarlberg
Austria	Ordination Dr. Nehoda	Innsbruck	Tirol
Austria	Ordination Dr. Peter Brock	Innsbruck	Tyrol
Austria	Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK	Innsbruck	Tirol
Austria	Ordination Dr. Mayr	Kufstein	Tirol
Austria	Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen	Wien
Austria	Universitätsklinik für Frauenheilkunde, AKH	Wien
Poland	CMR	Katowice
Poland	Provita Sp. z o.o. Fabryczna 13 D	Katowice
Poland	Centrum Zdrowia Kobiety Komed,	Kielce
Poland	Komed	Kielce
Poland	PZS Olesnica	Olesnica
Poland	Fem-Med	Poznan
Poland	Gaja Poradnie Lekarskie	Poznan
Poland	Bonus 2001 Sp. z o.o. Sp. K.	Skórzewo
Poland	Gabinety Lekarskie SIGNUM	Skórzewo
Poland	DC-MED., Dworcowa 5	Swidnica
Poland	Centrum medyczne Lux MED	Warsaw
Poland	Astimed Sp. z o.o.,	Warszawa
Poland	Centrum Medyczne LUX MED Swidnicka 40	Wroclaw
Slovakia	BESME s.r.o	Bánovce Nad Bebravou
Slovakia	MILLY s.r.o.	Bratislava
Slovakia	Gynedur s.r.o.	Dubnica Nad Váhom
Slovakia	MCM GYNPED s.r.o.	Dubnica Nad Váhom
Slovakia	Gyncentrum Nitra s.r.o.	Nitra
Slovakia	GYNAMA s.r.o.	Nove Mesto nad Vahom
Slovakia	BrenCare s.r.o	Poprad
Slovakia	GYNECARE s.r.o.	Púchov
Slovakia	Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia	Trencín

Sponsors (2)

Lead Sponsor	Collaborator
ProFem GmbH	Montavit Ges.m.b.H.

Countries where clinical trial is conducted

Austria,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Improvement of patient reported health related quality of life score at the end of the observation period using the EQ-5D questionnaire	Registration of changes of health related quality of life (HRQoL)- score values at 0, 6 and 12 months	0, 6 and12 months
Other	Sexual function related to pain and improvement thereof (see Annex I)	Evaluation of sexual function by changes of score values in a questionnaire regarding sexual function after 0, 6 and 12 months	0, 6 and12 months
Primary	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	Proportion of patients with clinical cure (absence of signs and symptoms of VVC) at 6, 8, 10 and 12 months after randomization	Registration of the number of clinically cured patients throughout the study period by determination of severity score values.	6, 8, 10, 12 months
Secondary	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)	Registration of patients with a severity score value of 0 after therapy of the acute phase at TOC visit	after 2 weeks
Secondary	Patient reported outcome of time to termination of clinical symptoms using the 11-point numeric rating scale (NRS) for burning, itching, soreness/irritation	Registration of duration of the acute episode by decrease of NRS values in a self-assessment tool, reported in a paper diary or an electronic patient reported outcome (ePRO) system	within 2 weeks after randomization
Secondary	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.	Registration of rapid pain release by a patient reported outcome tool by measuring the decrease of NRS values for burning, itching, soreness/irritation	48 hours