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

Primary Purpose

Recurrent Vulvovaginal Candidiasis

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Prof-001
Fluconazole 150 mg
Placebo cream
Placebo capsule
Sponsored by
ProFem GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Vulvovaginal Candidiasis focused on measuring Recurrent VVC, RVVC, Vulvovaginal candidiasis, ProF-001, Fluconazole, Vulvovaginitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Ordination Dr. Nehoda
  • Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK
  • Ordination Dr. Mayr
  • Ordination Dr. Peter Brock
  • Ordination Dr. Fischer
  • Universitätsklinik für Frauenheilkunde, AKH
  • Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen
  • Provita Sp. z o.o. Fabryczna 13 D
  • CMR
  • Centrum Zdrowia Kobiety Komed,
  • Komed
  • PZS Oleśnica
  • Fem-Med
  • Gaja Poradnie Lekarskie
  • Bonus 2001 Sp. z o.o. Sp. K.
  • Gabinety Lekarskie SIGNUM
  • Centrum medyczne Lux MED
  • Astimed Sp. z o.o.,
  • Centrum Medyczne LUX MED Swidnicka 40
  • DC-MED., Dworcowa 5
  • MILLY s.r.o.
  • BESME s.r.o
  • Gynedur s.r.o.
  • MCM GYNPED s.r.o.
  • Gyncentrum Nitra s.r.o.
  • GYNAMA s.r.o.
  • BrenCare s.r.o
  • GYNECARE s.r.o.
  • Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ProF-001 Group

Fluconazole Group

Arm Description

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

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)

Outcomes

Primary Outcome Measures

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)

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
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)
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
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.
Registration of rapid pain release by a patient reported outcome tool by measuring the decrease of NRS values for burning, itching, soreness/irritation

Full Information

First Posted
November 30, 2020
Last Updated
September 21, 2022
Sponsor
ProFem GmbH
Collaborators
Montavit Ges.m.b.H.
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1. Study Identification

Unique Protocol Identification Number
NCT04734405
Brief Title
A Phase IIb/III Study of Prof-001 for the Treatment of Patients With Recurrent Vulvovaginal Candidiasis (RVVC)
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
November 1, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ProFem GmbH
Collaborators
Montavit Ges.m.b.H.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Vulvovaginal Candidiasis
Keywords
Recurrent VVC, RVVC, Vulvovaginal candidiasis, ProF-001, Fluconazole, Vulvovaginitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Parallel-arm, Randomized, Active-controlled, Double-blind, Double-dummy
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
432 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ProF-001 Group
Arm Type
Experimental
Arm Description
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
Arm Title
Fluconazole Group
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Prof-001
Intervention Description
Prof-001 cream
Intervention Type
Drug
Intervention Name(s)
Fluconazole 150 mg
Intervention Description
Fluconazole capsule
Intervention Type
Drug
Intervention Name(s)
Placebo cream
Intervention Description
ointment base to mimic Prof-001
Intervention Type
Drug
Intervention Name(s)
Placebo capsule
Intervention Description
encapsulated lactose powder to mimic 150 mg fluconazole capsule
Primary Outcome Measure Information:
Title
Percentage of patients with at least one episode of clinical relapse of VVC during the 12 months study period.
Description
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)
Time Frame
after 12 months
Secondary Outcome Measure Information:
Title
Proportion of patients with clinical cure (absence of signs and symptoms of VVC) at 6, 8, 10 and 12 months after randomization
Description
Registration of the number of clinically cured patients throughout the study period by determination of severity score values.
Time Frame
6, 8, 10, 12 months
Title
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)
Description
Registration of patients with a severity score value of 0 after therapy of the acute phase at TOC visit
Time Frame
after 2 weeks
Title
Patient reported outcome of time to termination of clinical symptoms using the 11-point numeric rating scale (NRS) for burning, itching, soreness/irritation
Description
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
Time Frame
within 2 weeks after randomization
Title
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.
Description
Registration of rapid pain release by a patient reported outcome tool by measuring the decrease of NRS values for burning, itching, soreness/irritation
Time Frame
48 hours
Other Pre-specified Outcome Measures:
Title
Improvement of patient reported health related quality of life score at the end of the observation period using the EQ-5D questionnaire
Description
Registration of changes of health related quality of life (HRQoL)- score values at 0, 6 and 12 months
Time Frame
0, 6 and12 months
Title
Sexual function related to pain and improvement thereof (see Annex I)
Description
Evaluation of sexual function by changes of score values in a questionnaire regarding sexual function after 0, 6 and 12 months
Time Frame
0, 6 and12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert Kiss, Prof.
Organizational Affiliation
Universitätsklinik für Frauenheilkunde
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ordination Dr. Nehoda
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Ordination Dr. Mayr
City
Kufstein
State/Province
Tirol
ZIP/Postal Code
6330
Country
Austria
Facility Name
Ordination Dr. Peter Brock
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Ordination Dr. Fischer
City
Bregenz
State/Province
Vorarlberg
ZIP/Postal Code
6900
Country
Austria
Facility Name
Universitätsklinik für Frauenheilkunde, AKH
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen
City
Wien
ZIP/Postal Code
1210
Country
Austria
Facility Name
Provita Sp. z o.o. Fabryczna 13 D
City
Katowice
ZIP/Postal Code
40-611
Country
Poland
Facility Name
CMR
City
Katowice
ZIP/Postal Code
40-628
Country
Poland
Facility Name
Centrum Zdrowia Kobiety Komed,
City
Kielce
ZIP/Postal Code
25-435
Country
Poland
Facility Name
Komed
City
Kielce
ZIP/Postal Code
25-435
Country
Poland
Facility Name
PZS Oleśnica
City
Oleśnica
ZIP/Postal Code
56-400
Country
Poland
Facility Name
Fem-Med
City
Poznań
ZIP/Postal Code
60-512
Country
Poland
Facility Name
Gaja Poradnie Lekarskie
City
Poznań
ZIP/Postal Code
61-251
Country
Poland
Facility Name
Bonus 2001 Sp. z o.o. Sp. K.
City
Skórzewo
ZIP/Postal Code
60-185
Country
Poland
Facility Name
Gabinety Lekarskie SIGNUM
City
Skórzewo
ZIP/Postal Code
60-185
Country
Poland
Facility Name
Centrum medyczne Lux MED
City
Warsaw
ZIP/Postal Code
02-672
Country
Poland
Facility Name
Astimed Sp. z o.o.,
City
Warszawa
ZIP/Postal Code
01-875
Country
Poland
Facility Name
Centrum Medyczne LUX MED Swidnicka 40
City
Wroclaw
ZIP/Postal Code
50-024
Country
Poland
Facility Name
DC-MED., Dworcowa 5
City
Świdnica
ZIP/Postal Code
58-100
Country
Poland
Facility Name
MILLY s.r.o.
City
Bratislava
Country
Slovakia
Facility Name
BESME s.r.o
City
Bánovce Nad Bebravou
Country
Slovakia
Facility Name
Gynedur s.r.o.
City
Dubnica Nad Váhom
Country
Slovakia
Facility Name
MCM GYNPED s.r.o.
City
Dubnica Nad Váhom
Country
Slovakia
Facility Name
Gyncentrum Nitra s.r.o.
City
Nitra
Country
Slovakia
Facility Name
GYNAMA s.r.o.
City
Nove Mesto nad Vahom
Country
Slovakia
Facility Name
BrenCare s.r.o
City
Poprad
Country
Slovakia
Facility Name
GYNECARE s.r.o.
City
Púchov
Country
Slovakia
Facility Name
Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia
City
Trenčín
Country
Slovakia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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