Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
190
Countries
1
Sites
1
Breast cancer patients on endocrine therapy (AI or SERM) with symptoms of vulvovaginal atrophy
In this active-controlled randomized trial two main primary objectives have been determined. Firstly, the efficacy of the different treatment regimens will be assessed. The assessment will be based on PROMs and clinical evaluations such as vaginal pH and the vaginal maturation index, the latter a direct microscopic eva…
Key facts
- Sponsor
- Universitair Ziekenhuis Gent
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 23 Jun 2025 → ongoing
- Decision date (initial)
- 2024-06-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Kom Op Tegen Kanker
External identifiers
- EU CT number
- 2024-510845-33-00
- EudraCT number
- 2021-001921-31
- ClinicalTrials.gov
- NCT05562518
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Therapy
In this active-controlled randomized trial two main primary objectives have been determined.
Firstly, the efficacy of the different treatment regimens will be assessed. The assessment will be based on PROMs and clinical evaluations such as vaginal pH and the vaginal maturation index, the latter a direct microscopic evaluation of the vaginal epithelium.
Secondly, safety of the different groups will be assessed. Although previous research already indicated no increased breast cancer recurrence, there is no direct comparative data available towards the different available treatment regimes. This will be tackled in this study. Evaluation will be done be measuring sex hormone concentrations systemically, which will be a surrogate for safety evaluation.
Secondary objectives 1
- The secondary objective in this study is the identification of microbial alterations after treatment initiation. Identification of these alterations can help in further understanding of the pathophysiology of vulvovaginal atrophy and potentially create opportunities for new treatment strategies towards vulvovaginal atrophy in breast cancer patients on endocrine therapy.
Conditions and MedDRA coding
Breast cancer patients on endocrine therapy (AI or SERM) with symptoms of vulvovaginal atrophy
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Active-controlled, randomized phase IV Mono-centric active-controlled, randomized phase IV trial
|
Randomised Controlled | None | Oekolp treatment: 1 vaginal ovule daily for three consecutive weeks, followed by 1 vaginal ovule 2 times per week Intratose treatment: 1 vaginal ovule daily Premeno Duo treatment: 1 vaginal ovule daily for ten consecutive days, followed by 1 vaginal ovule 2 times per week Gynoflor treatment: 1 vaginal ovule daily for twelve consecutive days, followed by 1 vaginal ovule 2 times per week |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Breast cancer patient
- Current endocrine therapy (AI or SERM)
- Postmenopausal status, defined by: 12 months amenorrhoe or 6 months amenorrhoe and FSH level of >40 mIU/mL or Induced postmenopause (ovarian function suppression using GnRH-analogue) >6 weeks after bilateral oophorectomy or
- Presence of one or more symptoms of vulvovaginal atrophy (dyspareunia, dryness, irritation)
Exclusion criteria 4
- A history of vulvar or vaginal surgery. Inclusion is possible after hysterectomy. For these subjects no microbiome sampling will be performed. Microbiome analysis is not performed for these subjects.
- Current other vulvar or vaginal disease (e.g. dysplasia, fungal infection,…)
- Recent use of antibiotics/antifungals/corticosteroids (less than 1 month)
- Current use of vaginal hormonal treatment or vaginal moisturizer (inclusion is possible after a washout period of 4 weeks)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint of this study is the efficacy of the implemented treatment regimes. Efficacy will be assessed based on patient-reported outcome measurements, being two validated questionnaires: EQ5D-questionnaire (Appendix 1) and the FACT-ES questionnaire (Appendix 2). This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks).
Secondary endpoints 1
- The secondary endpoint is the safety of the implemented treatments. As a surrogate for safety, blood serum concentration of sex steroid hormones will be determined. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 8
PRD7290517 · Product
- Active substance
- Prasterone
- Pharmaceutical form
- PESSARY
- Route of administration
- VAGINAL USE
- Max daily dose
- 6.5 mg milligram(s)
- Max total dose
- 546 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03XX01 — -
- Marketing authorisation
- EU/1/17/1255/001
- MA holder
- ENDOCEUTICS S.A.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7291038 · Product
- Active substance
- Prasterone
- Pharmaceutical form
- PESSARY
- Route of administration
- VAGINAL USE
- Max daily dose
- 6.5 mg milligram(s)
- Max total dose
- 546 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03XX01 — -
- Marketing authorisation
- EU/1/17/1255/001
- MA holder
- ENDOCEUTICS S.A.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7291060 · Product
- Active substance
- Prasterone
- Pharmaceutical form
- PESSARY
- Route of administration
- VAGINAL USE
- Max daily dose
- 6.5 mg milligram(s)
- Max total dose
- 546 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03XX01 — -
- Marketing authorisation
- EU/1/17/1255/001
- MA holder
- ENDOCEUTICS S.A.
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD5900329 · Product
- Active substance
- Estriol
- Pharmaceutical form
- VAGINAL TABLET
- Route of administration
- VAGINAL USE
- Max daily dose
- 900 mg milligram(s)
- Max total dose
- 28800 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03CC06 — ESTRIOL
- Marketing authorisation
- BE178062
- MA holder
- GEDEON RICHTER PLC.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Gynoflor tabletten voor vaginaal gebruik
PRD5900330 · Product
- Active substance
- Estriol
- Pharmaceutical form
- VAGINAL TABLET
- Route of administration
- VAGINAL USE
- Max daily dose
- 900 mg milligram(s)
- Max total dose
- 28800 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03CC06 — ESTRIOL
- Marketing authorisation
- BE178062
- MA holder
- GEDEON RICHTER PLC.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD5900331 · Product
- Active substance
- Estriol
- Pharmaceutical form
- VAGINAL TABLET
- Route of administration
- VAGINAL USE
- Max daily dose
- 900 mg milligram(s)
- Max total dose
- 28800 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03CC06 — ESTRIOL
- Marketing authorisation
- BE178062
- MA holder
- GEDEON RICHTER PLC.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD7290891 · Product
- Active substance
- Prasterone
- Pharmaceutical form
- PESSARY
- Route of administration
- VAGINAL USE
- Max daily dose
- 6.5 mg milligram(s)
- Max total dose
- 546 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03XX01 — -
- Marketing authorisation
- EU/1/17/1255/001
- MA holder
- ENDOCEUTICS S.A.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD5946312 · Product
- Active substance
- Estriol
- Pharmaceutical form
- PESSARY
- Route of administration
- VAGINAL USE
- Max daily dose
- 0.03 mg milligram(s)
- Max total dose
- 1.17 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- G03CA04 — ESTRIOL
- Marketing authorisation
- BE526631
- MA holder
- DR. KADE PHARMAZEUTISCHE FABRIK GMBH
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Ziekenhuis Gent
- Sponsor organisation
- Universitair Ziekenhuis Gent
- Address
- Corneel Heymanslaan 10
- City
- Gent
- Postcode
- 9000
- Country
- Belgium
Scientific contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- Prof. Dr. Hans Verstraelen
Public contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- Prof. Dr. Hans Verstraelen
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 190 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2022-04-07 | 2022-05-09 | 2026-03-02 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-59273
- Halt date
- 2024-11-19
- Member states concerned
- Belgium
- Publication date
- 2024-11-25
- Reason
- Sponsor decision
- Explanation
- The manufacturer of Premeno Duo has updated the naming of the product to Premeno.
Additionally, due to amended laws and regulations, Premeno was reformulated.
This means the composition has changed slightly, the active ingredient Hyaluronic Acid has remained the same.
The loading has also been updated to 1 ovule daily for 14 days instead of daily for 10 days previously.
Due to this new dosage, a pack of Premeno will now contain 14 ovules instead of the 10 ovules. Since this study use this product according to the leaflet and standard use, the investigators want to adapt the duration of taking Premeno daily from 10 to 14 days.
These changes have a substantial impact in the study protocol and treatment of newly included subjects in the trial. Additionally, the dosing duration is also mentioned in de Informed Consent Forms and on the labeling.
For this reason, the study has been put on temporary halt and a substantial modification will be submitted to address the necessary changes to the study documentation. Upon authorisation of the substantial modification, a Restart of the Trial will be notified and inclusion will be started again. - Follow-up measures
- Currently, no patients are treated with Premeno. There is one patient in active treatment in one of the other treatment arms. This patient can remain in treatment. No new patients will be included in the trial until receipt of SM01 authorisation. After this, a Study restart will be notified within the legally binding timeframe.
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 27 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-510845-33-00__for publication | 2.0 |
| Protocol (for publication) | D1_Protocol 2024-510845-33-00__for publication 1 | 1.1 |
| Protocol (for publication) | D2_Medical Device_Premeno-Duo-CE Certifcate_for publication | 2.0 |
| Protocol (for publication) | D2_Medical Device_Premeno-Duo-Conformity_for publication | 2.0 |
| Protocol (for publication) | D2_Medical Device_Premeno-Duo-Leaflet_for publication | 2.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_for publication | 1 |
| Recruitment arrangements (for publication) | K2_POSTERFLYER_for publication | 1.0 |
| Recruitment arrangements (for publication) | K3_Probando advertisement material | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF NL__for publication | 2.0 |
| Subject information and informed consent form (for publication) | L2_Informed consent procedure_for publication | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Gynoflor_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Gynoflor_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Gynoflor_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Intrarosa_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Intrarosa_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Intrarosa_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Intrarosa_for publication | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Oekolp__for publication | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis Dutch 2024-510845-33-00_Clean__for publication | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis ENG 2024-510845-33-00_Clean__for publication | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis French 2024-510845-33-00_Clean__for publication | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis German 2024-510845-33-00_Clean__for publication | 1 |
| Synopsis of the protocol (for publication) | D2_Subject card NL_Gynoflor_Clean_for publication | 2.0 |
| Synopsis of the protocol (for publication) | D2_Subject card NL_Intrarosa_Clean_for publication | 2.0 |
| Synopsis of the protocol (for publication) | D2_Subject card NL_Oekolp_Clean_for publication | 2.0 |
| Synopsis of the protocol (for publication) | D2_Subject card NL_Premeno_Clean_For publication | 2.0 |
| Synopsis of the protocol (for publication) | Document regarding transition GRACE_for publication | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-18 | Belgium | Acceptable 2024-06-27
|
2024-06-27 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-13 | Belgium | Acceptable 2025-06-13
|
2025-06-20 |