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

Sponsor

ProFem GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04734405

Collaborator

Montavit Ges.m.b.H. (Industry)

432

Enrollment

Locations

Arms

Anticipated Duration (Months)

14.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Vulvovaginal Candidiasis	Drug: Prof-001 Drug: Fluconazole 150 mg Drug: Placebo cream Drug: Placebo capsule	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

432 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel-arm, Randomized, Active-controlled, Double-blind, Double-dummyParallel-arm, Randomized, Active-controlled, Double-blind, Double-dummy

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Prof-001 Prof-001 cream Drug: Placebo capsule encapsulated lactose powder to mimic 150 mg fluconazole capsule
Active Comparator: 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: 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 Fluconazole capsule Drug: Placebo cream ointment base to mimic Prof-001

Arm

Intervention/Treatment

Experimental: 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

Drug: Prof-001

Prof-001 cream

Drug: Placebo capsule

encapsulated lactose powder to mimic 150 mg fluconazole capsule

Active Comparator: 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: 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

Fluconazole capsule

Drug: Placebo cream

ointment base to mimic Prof-001

Outcome Measures

Primary Outcome Measures

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

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]
Registration of the number of clinically cured patients throughout the study period by determination of severity score values.
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]
Registration of patients with a severity score value of 0 after therapy of the acute phase at TOC visit
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]
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
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]
Registration of rapid pain release by a patient reported outcome tool by measuring the decrease of NRS values for burning, itching, soreness/irritation

Other Outcome Measures

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]
Registration of changes of health related quality of life (HRQoL)- score values at 0, 6 and 12 months
Sexual function related to pain and improvement thereof (see Annex I) [0, 6 and12 months]
Evaluation of sexual function by changes of score values in a questionnaire regarding sexual function after 0, 6 and 12 months

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ordination Dr. Nehoda	Innsbruck	Tirol	Austria	6020
2	Ordination Dr. Shihab	Innsbruck	Tirol	Austria	6020
3	Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK	Innsbruck	Tirol	Austria	6020
4	Ordination Dr. Mayr	Kufstein	Tirol	Austria	6330
5	Ordination Dr. Peter Brock	Innsbruck	Tyrol	Austria	6020
6	Ordination Dr. Fischer	Bregenz	Vorarlberg	Austria	6900
7	Universitätsklinik für Frauenheilkunde, AKH	Wien		Austria	1090
8	Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen	Wien		Austria	1210
9	Provita Sp. z o.o. Fabryczna 13 D	Katowice		Poland	40-611
10	CMR	Katowice		Poland	40-628
11	Centrum Zdrowia Kobiety Komed,	Kielce		Poland	25-435
12	Komed	Kielce		Poland	25-435
13	PZS Oleśnica	Oleśnica		Poland	56-400
14	Fem-Med	Poznań		Poland	60-512
15	Gaja Poradnie Lekarskie	Poznań		Poland	61-251
16	Bonus 2001 Sp. z o.o. Sp. K.	Skórzewo		Poland	60-185
17	Gabinety Lekarskie SIGNUM	Skórzewo		Poland	60-185
18	Centrum medyczne Lux MED	Warsaw		Poland	02-672
19	Astimed Sp. z o.o.,	Warszawa		Poland	01-875
20	Centrum Medyczne LUX MED Swidnicka 40	Wroclaw		Poland	50-024
21	DC-MED., Dworcowa 5	Świdnica		Poland	58-100
22	MILLY s.r.o.	Bratislava		Slovakia
23	BESME s.r.o	Bánovce Nad Bebravou		Slovakia
24	Gynedur s.r.o.	Dubnica Nad Váhom		Slovakia
25	MCM GYNPED s.r.o.	Dubnica Nad Váhom		Slovakia
26	Gyncentrum Nitra s.r.o.	Nitra		Slovakia
27	GYNAMA s.r.o.	Nove Mesto nad Vahom		Slovakia
28	BrenCare s.r.o	Poprad		Slovakia
29	GYNECARE s.r.o.	Púchov		Slovakia
30	Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia	Trenčín		Slovakia