Investigation of 3 different doses of a newly developed vaginal ring releasing estriol for the treatment of vaginal atrophy - a placebo-controlled, double-blind, combined dose-finding and proof-of-concept trial with parallel-group design in postmenopausal women

Overview

Sponsor-declared trial summary

Key facts

Sponsor

SocraTec R&D Concepts in Drug Research and Development GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

16 Jul 2025 → 1 Jun 2026

Decision date (initial)

2025-06-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

- Descriptive evaluation of the change in the cytologic pattern of vaginal epithelium after 90 days of each treatment
- Descriptive evaluation of the change in vaginal pH after 90 days of each treatment
- Descriptive evaluation of systemic total E3 exposure in a subgroup of patients (PK subgroup)

Conditions and MedDRA coding

Vaginal atrophy

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Age: 45 years or older
2. 2. Postmenopausal state defined as last spontaneous menstruation at least 1 year prior to the study and FSH (serum) ≥ 40 IU/l (≥ 40 E/l)
3. 3. Vaginal Maturation Value (MV) ≤ 50% at screening
4. 4. Vaginal pH > 5.0 at screening
5. 5. At least one subjective symptom of VA (dryness, pain/burning sensation, pruritus, discharge, dysuria, urinary incontinence, dyspareunia) rated at a score of ≥ 65 on the Visual Analogue Scale (VAS)
6. 6. Non-smoker or ex-smoker for at least 3 months
7. 7. Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the participants in this clinical trial

Exclusion criteria 30

1. 1. History or presence of cardiac and/or haematological diseases or pathological findings, which, in the opinion of the investigator, might interfere with the safety or tolerability of the active ingredient
2. 2. History or presence of hepatic and/or renal diseases or pathological findings, which, in the opinion of the investigator, might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
3. 3. History or presence of relevant Central Nervous System (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders, which in the opinion of the investigator, might affect the safety of the participant
4. 4. Known allergic reactions/hypersensitivity to the active ingredient used or to constituents of the pharmaceutical preparations
5. 5. Participants with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
6. 6. Systolic blood pressure > 139 mmHg
7. 7. Diastolic blood pressure >89 mmHg
8. 8. Pulse rate < 50 bpm or > 100 bpm
9. 9. Any clinically relevant abnormality as observed during breast examination at screening
10. 10. Any laboratory value outside of normal and judged by investigator as relevant for participation under safety considerations
11. 11. Any further contraindication to estrogen therapy; Known, past or suspected breast cancer; Known, past or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer); Current or undiagnosed genital bleeding; Untreated endometrial hyperplasia; Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism); Known thrombophilic disorders; Active or recent (within the last 24 months) arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction) if not cured without cardiovascular consequences; Porphyria
12. 12. If any of the conditions listed below are present or have occurred previously. Patients might participate if either these conditions have not aggravated during pregnancy or previous sex hormone treatment, or if they are judged by the investigator not to pose a current safety risk for the participant; Leiomyoma (uterine fibroids) or endometriosis; Risk factors for thromboembolic disorders; Risk factors for oestrogen-dependent tumours, e.g. 1st degree relative for breast cancer; Untreated or uncontrolled hypertension; Liver adenoma or estrogen-dependent liver disorders (e.g. liver cysts, liver angioma); uncontrolled Diabetes mellitus; Cholelithiasis; Migraine or category II or higher non-migraine headaches (grading of non-migraine headaches acc. to Sjaastad et al. 2002); Systemic lupus erythematosus; A history of endometrial hyperplasia (endometrial thickness of ≥5 mm); Epilepsy; Asthma; Otosclerosis; Endometrial polyps
13. 13. Diagnosis of a cervical smear: findings classified in a group higher than IIa according to the Munich III nomenclature or history of documented abnormal cervical smear (higher than IIa) within one year of screening
14. 14. Confirmation of endometrial thickness of ≥5 mm
15. 15. Untreated vaginal infection that would hinder the insertion of the ring according to the decision of the investigator
16. 16. The following washout periods must be observed before screening: 1 week or longer for prior non-hormonal vaginal or vulvar treatment (including cosmetics expected to affect vaginal pH such as special feminine wash gels); 4 weeks or longer for prior vaginal hormonal products (rings, creams, gels); 4 weeks or longer for prior transdermal estrogen alone or estrogen/progestin products; 8 weeks or longer for prior oral estrogen and/or progestin therapy; 8 weeks or longer for prior intrauterine progestin therapy; 8 weeks or longer for prior testosterone or testosterone derivatives, DHEA, tibolone, or SERMs by any route; 3 months or longer for prior progestin implants and estrogen alone injectable drug therapy; 6 months or longer for prior estrogen pellet therapy or progestin injectable drug therapy
17. 17. Use of systemic or intravaginal corticosteroids within 8 weeks prior to the IMP administration
18. 18. Treatment with strong inductors or inhibitors of CYP3A4, e.g. anticonvulsants (barbiturates, hydantoins, carbamazepine), certain antibiotics (e.g. erythromycin, clarithromycin, telithromycin), antimycotics (e.g. ketoconazole, itraconazole) and other antiinfective medicinal products (e.g. rifampicin, rifabutin, nevirapine, efavirenz); phenylbutazone; ritonavir and nelfinavir; preparations based on medicinal plants that contain St. John’s Wort within 2 weeks prior to the IMP administration
19. 19. Women with hysterectomy and/or bilateral oophorectomy
20. 20. Acute or chronic diseases which may interfere with the aims of the clinical trial
21. 21. Vaginal descensus or other condition which might interfere with the vaginal application of IMP
22. 22. History of or current drug or alcohol dependence or abuse
23. 23. Participation in a clinical trial with administration of any investigational medicinal product during the last 2 months prior to screening
24. 24. Simultaneous participation in another clinical trial with active ingredients
25. 25. Participant is judged by the Investigator to be unsuitable for any reason
26. 26. Non-availability of prompt access to eDiary at any time
27. 27. Participants suspected or known not to follow instructions
28. 28. Participants who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
29. 29. Participant is vulnerable such as detained or committed to an institution by a court of law or by legal authorities or has close affiliation with the sponsor or the investigational site (e.g. a close relative, dependent person (e.g. employee or student))
30. 30. Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Change from baseline in vaginal Maturation Value (MV) after 90 days of treatment
2. Change from baseline in % of vaginal superficial cells after 90 days of treatment
3. Change from baseline in % of vaginal parabasal cells after 90 days of treatment
4. Change from baseline in vaginal pH after 90 days of treatment
5. Proportion of responders with a vaginal pH ≤ 5 after 90 days of treatment
6. Total (AUC) E3 exposure over the course of treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

SocraTec R&D Concepts in Drug Research and Development GmbH

Sponsor organisation

SocraTec R&D Concepts in Drug Research and Development GmbH

Address

Im Setzling 35, Bommersheim Bommersheim

City

Oberursel (Taunus)

Postcode

61440

Country

Germany

Scientific contact point

Organisation

SocraTec R&D Concepts in Drug Research and Development GmbH

Contact name

Scientific Director of the clinical trial

Public contact point

Organisation

SocraTec R&D Concepts in Drug Research and Development GmbH

Contact name

Clinical trial information

Third parties 6

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications