Recurrent Vulvovaginal CandidiasisPhase 2/3NCT04734405
A Phase IIb/III Study of Prof-001 for the Treatment of Patients With Recurrent Vulvovaginal Candidiasis (RVVC)
A Phase 2/3 study testing Prof-001 and Fluconazole 150 mg in people with Recurrent Vulvovaginal Candidiasis, run by ProFem GmbH at 29 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Vulvovaginal Candidiasis
- What is being tested?
- Prof-001 and Fluconazole 150 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 432 participants
- Where
- 29 sitesin 3 countries
- Study dates
- 1 Oct 2019to 30 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
29 sites in 3 countries.
29 sites in 3 countries
Poland13 sites
Provita Sp. z o.o. Fabryczna 13 D
Katowice, 40-611
CMR
Katowice, 40-628
Centrum Zdrowia Kobiety Komed,
Kielce, 25-435
Komed
Kielce, 25-435
PZS Oleśnica
Oleśnica, 56-400
Fem-Med
Poznan, 60-512
Gaja Poradnie Lekarskie
Poznan, 61-251
Bonus 2001 Sp. z o.o. Sp. K.
Skórzewo, 60-185
Gabinety Lekarskie SIGNUM
Skórzewo, 60-185
DC-MED., Dworcowa 5
Swidnica, 58-100
Astimed Sp. z o.o.,
Warsaw, 01-875
Centrum medyczne Lux MED
Warsaw, 02-672
Centrum Medyczne LUX MED Swidnicka 40
Wroclaw, 50-024
Slovakia9 sites
BESME s.r.o
Bánovce nad Bebravou
MILLY s.r.o.
Bratislava
Gynedur s.r.o.
Dubnica nad Váhom
MCM GYNPED s.r.o.
Dubnica nad Váhom
Gyncentrum Nitra s.r.o.
Nitra
GYNAMA s.r.o.
Nové Mesto nad Váhom
BrenCare s.r.o
Poprad
GYNECARE s.r.o.
Púchov
Gyneka s.r.o., Privatna gynekologicko porodnicka ambulancia
Trenčín
Austria7 sites
Ordination Dr. Fischer
Bregenz, Vorarlberg, 6900
Ordination Dr. Nehoda
Innsbruck, Tyrol, 6020
Ordination Dr. Peter Brock
Innsbruck, Tyrol, 6020
Universitätsklinik für Gynäkologie und Geburthilfe, Uni-Klinik IBK
Innsbruck, Tyrol, 6020
Ordination Dr. Mayr
Kufstein, Tyrol, 6330
Universitätsklinik für Frauenheilkunde, AKH
Vienna, 1090
Ambulatorium für Pilzinfektionen und andere infektiöse venero-dermatologische Erkrankungen
Vienna, 1210
About this study
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
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.
Read the 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.
- Conditions
- Recurrent Vulvovaginal Candidiasis
- Being tested
- Prof-001, Fluconazole 150 mg, Placebo cream, Placebo capsule
- Keywords
- Recurrent VVC, RVVC, Vulvovaginal candidiasis, ProF-001, Fluconazole, Vulvovaginitis
- Medical subject headings
- Candidiasis, Vulvovaginal, Vulvovaginitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prof-001Drug
Prof-001 cream
Fluconazole 150 mgDrug
Fluconazole capsule
Placebo creamDrug
ointment base to mimic Prof-001
Placebo capsuleDrug
encapsulated lactose powder to mimic 150 mg fluconazole capsule
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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) Receives: Drug: Fluconazole 150 mg; Drug: Placebo cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Registration of the number of clinically cured patients throughout the study period by determination of severity score values.
Measured: 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)
Registration of patients with a severity score value of 0 after therapy of the acute phase at TOC visit
Measured: 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
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
Measured: 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.
Registration of rapid pain release by a patient reported outcome tool by measuring the decrease of NRS values for burning, itching, soreness/irritation
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start1 Oct 2019
- Primary completion1 Nov 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Vulvovaginal CandidiasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel-arm, Randomized, Active-controlled, Double-blind, Double-dummy
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 432 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ProFem GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Montavit Ges.m.b.H.
- Responsible party
- Sponsor
- Investigators
- Herbert Kiss, Prof., Principal investigator, Universitätsklinik für Frauenheilkunde
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734405
- Sponsor's protocol ID
- ProF-001 IIb-III
- Status last verified
- Sep 2022
- First submitted
- 30 Nov 2020
- Last updated
- 22 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abdelkader SI, Aboelenin SA, Abdelhafez RA, Nabhan AF. Oral versus topical maintenance antifungal therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis. BMC Womens Health. 2026 Mar 18;26(1):196. doi: 10.1186/s12905-026-04356-8.
PubMed 41845293
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04734405
- Acronym / sponsor ID
- ProF-001 IIb-III
- Conditions
- Recurrent Vulvovaginal Candidiasis
- Keywords
- Recurrent VVC, RVVC, Vulvovaginal candidiasis, ProF-001, Fluconazole, Vulvovaginitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 432 participants (estimated)
- Lead sponsor
- ProFem GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Montavit Ges.m.b.H.
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel-arm, Randomized, Active-controlled, Double-blind, Double-dummy
| Arm | Type | Receives |
|---|---|---|
| ProF-001 Group | Experimental | Drug: Prof-001, Drug: Placebo capsuleProF-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 | Active comparator | Drug: Fluconazole 150 mg, Drug: Placebo creamFluconazole 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prof-001Prof-001 cream | Drug | ProF-001 Group |
| Fluconazole 150 mgFluconazole capsule | Drug | Fluconazole Group |
| Placebo creamointment base to mimic Prof-001 | Drug | Fluconazole Group |
| Placebo capsuleencapsulated lactose powder to mimic 150 mg fluconazole capsule | Drug | ProF-001 Group |
Primary outcome
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)
4 secondary outcomes
Proportion of patients with clinical cure (absence of signs and symptoms of VVC) at 6, 8, 10 and 12 months after randomization
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 48 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Derived from this study: PubMed 41845293Abdelkader SI, Aboelenin SA, Abdelhafez RA, Nabhan AF. Oral versus topical maintenance antifungal therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis. BMC Womens Health. 2026 Mar 18;26(1):196. doi: 10.1186/s12905-026-04356-8.
- Individual participant dataSharing planned: No
Related trials for Recurrent Vulvovaginal Candidiasis
Active, not recruitingPhase 1/2
Assessing the Safety, Immune Response, and Early Efficacy of a Candida Vaccine in Women With Recurrent Vulvovaginal Candidiasis: A Randomized Controlled Study
Recurrent Vulvovaginal Candidiasis
RecruitingPhase 3
The Effect of Medical Grade Honey Formulation (L-Mesitran) Administration on Recurrent Vulvovaginal Candidiasis Symptoms
Candidiasis, Vulvovaginal, Recurrent Candidiasis of Vagina
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Herbert Kiss, Prof. principal investigator
Universitätsklinik für Frauenheilkunde
29 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Prof-001 and Fluconazole 150 mg in people with Recurrent Vulvovaginal Candidiasis, run by ProFem GmbH at 29 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Poland, Slovakia, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with at least one episode of clinical relapse of VVC during the 12 months study period. (time frame: after 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04734405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022; AzTrials last refreshed its copy on 26 Oct 2026.