A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Influence of Estetrol (E4) on Hair Parameters in Postmenopausal Women (Pilot Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Estetra

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

21 Sep 2023 → 28 Jul 2025

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Estetra Srl, Belgium

External identifiers

EU CT number

2024-517890-26-00

EudraCT number

2022-002642-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Efficacy:
• assess the influence of treatment with E4 20 mg compared with
placebo on hair growth parameters in postmenopausal women with
female pattern hair loss by quantitative hair measurement (Target Area
Hair Count [TAHC]) of non-vellus hair at week 22 and Target Area Hair
Width (TAHW) at week 22), in a 6-month pilot study.
Safety:
• evaluate the general safety of treatment with E4 20 mg compared with
placebo
• evaluate the effect of treatment with E4 20 mg on the endometrium in
non-hysterectomized (NH) subjects compared with placebo
• evaluate the frequency (number of days) of vaginal bleeding in NH
subjects treated with E4 20 mg compared with placebo

Secondary objectives 1

1. Efficacy: assess the influence of treatment with E4 20 mg compared with placebo on additional hair parameters by: •Quantitative hair measurement of TAHC of non-vellus hair at week 10 • Quantitative hair measurement of TAHC of vellus/vellus like (miniaturized ) hair at week 10 and 22 • Quantitative hair measurement of TAHW at week 10; • SSA of scalp hair growth (Hair Growth Assessment [HGA], Hair Growth Index [HGI], Hair Growth Satisfaction Scale [HGSS]) at week 10 and 22; • Investigator global assessment (IGA) of scalp hair growth at week 10 and 22.

Conditions and MedDRA coding

postmenopausal women with vasomotor menopausal symptoms

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Signed and dated written IC form and any required privacy authorization prior to the initiation of any study procedure, after the nature of the study has been explained according to local regulatory requirements. 2. Females, ≥40 to ≤65 years of age (inclusive) at randomization/treatment allocation visit with vasomotor menopausal symptoms. 3. Postmenopausal status defined as any of the following: a. For NH subjects: ‒ At least 12 months of spontaneous amenorrhea with serum FSH >40 mIU/mL and E2 <20 pg/mL (values obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20). ‒ Or at least 6 months postsurgical bilateral oophorectomy . b. For hysterectomized subjects: ‒ Serum FSH >40 mIU/mL and E2 <20 pg/mL (values obtained after washout of estrogen/progestin containing drug, see exclusion criteria 18 and 20). ‒ or at least 6 months postsurgical bilateral oophorectomy2. 4. For subjects who have undergone hysterectomy and/or bilateral oophorectomy: documented surgery must have occurred at least 6 months prior to the start of screening. Hysterectomy can be total or subtotal (i.e., cervix was not removed). 5. For NH subjects: uterus with bi-layer endometrial thickness ≤ 4 mm on TVUS. 6. Body mass index (BMI) at screening between 18.5 kg/m² up to ≤35.0 kg/m², inclusive. 7. A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening . 8. Good physical and mental health, in the judgement of the Investigator as based on medical history, physical and gynecological examination, and clinical assessments performed prior to Visit 1. 9. Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions. 10. Able and willing to complete study diaries and questionnaires. For hair/scalp conditions: 11. Decrease in hair density on the top of the scalp, relative to the sides and back of the scalp, with scalp hair density in involved density area stages n. 2 to n. 6 on the Savin Density Scale, 12. Subject is willing to maintain the same hairstyle, hair length, and hair color throughout the study (implying the same hair coloring interval prior to the approved photo 13. Subject agrees to continue her other general hair care products and regimen for the entire study. 14. Subject agrees to maintain same dietary and supplement pattern.

Exclusion criteria 1

1. 1.History of malignancy 2.Healthy women in terms of the research project < 50 years of age needing mammography (compare §137 StrlSchV para 4) 3.Pregnant or breastfeeding women (compare §137 StrlSchV para 1) 4.Minors and persons not able to understand the nature, significance, scope and risks of application of radioactive or ionizing radiation and to direct their will accordingly (compare §136 StrlSchV para 1) 5.Healthy women in terms of the research project who were exposed to radioactive or ionizing radiation for the purpose of clinical research or treatment within the past 10 years if the new exposure according to this protocol exceeds 10 mSv (compare §137 StrlSchV para 3) 6.Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer 7.Subjects with uterus and/or cervix who have a cervical smear with atypical squamous cells of undetermined significance or higher 8.For subjects with uterus and/or cervix at Screening: a Presence of uterine cancer, endometrial hyperplasia or disordered proliferative endometrium b Presence of endometrial polyp(s) c Undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding d Any uterine/endometrial abnormality that contraindicates the use of estrogen and/or progestin therapy 9.Systolic BP higher than 139 mmHg, diastolic BP higher than 89 mmHg during Screening 10.History of venous or arterial thromboembolic disease or first-degree family history of VTE 11.History of known acquired or congenital coagulopathy or abnormal coagulation factors, including known thrombophilia 12.Laboratory values of glycated hemoglobin above 7.5% 13.Current smokers 14.Presence or history of gallbladder disease unless cholecystectomy has been performed 15.Systemic lupus erythematosus 16.Any malabsorption disorder including gastric bypass surgery 17.History of acute liver disease in 12 months before screening, or presence or history of chronic or severe liver disease, or liver tumors 18.Chronic or current acute renal impairment (estimated glomerular filtration rate 34.Planned surgery during the clinical study 35.Institutionalization because of legal or regulatory order hair/scalp condition: 36.Dermatological disorders of the scalp in the target region possibly interfering with the examination method 37.Skin pathology or condition interfere with the evaluation of the IMP or requires use of interfering topical, systemic or surgical therapy 38.History or any signs of hyperandrogenemia 39.Current/recent history (within 6 months prior Screening) of hair weaves, non-breathable wigs or hair bonding 40.Scalp hair transplants at any time 41.History or active hair loss due to diffuse telogen effluvium, alopecia areata, scarring alopecia, trichotillomania, or conditions/diseases other than AGA 42.current/recent history of severe dietary or weight changes or has a history of eating disorder(s) (within 6 months prior Screening), any history of bariatric surgery; macro- or micro-nutrient deficiencies within the last 6 months and/or any current diagnosis of unstable malabsorptive disease 43.Use of specific topical preparations or procedures on the scalp for different time periods prior to baseline (detailed list see protocol) 44.Use of specific systemic medications or procedures for different time periods (detailed list see protocol) 45.Unwilling to receive a dot tattoo on scalp

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in TAHC (non-vellus) and TAHW (non-vellus and vellus/vellus like hair) at Week 22 vs placebo; Safety endpoints: Frequency of TE(S)AEs; Categorical changes in physical, TVUS, vital signs, breast exam, and lab results at each time point; Change from baseline in endometrial thickness ; Proportion of women with vaginal bleeding/spotting per 28-day treatment cycle with E4 20 mg or placebo; Proportion of women with amenorrhea per 28-day treatment cycle with E4 20 mg or placebo

Secondary endpoints 1

1. Change from baseline: in TAHC (non-vellus) at Week 10 vs placebo; in TAHC (vellus/vellus like hair) at Weeks 10 and 22 vs placebo; in TAHW (non-vellus) at Week 10 vs placebo; in TAHW (vellus/vellus like hair) at Weeks 10 and 22 vs placebo; HGA score at Weeks 10 and 22 vs placebo; HGI at Weeks 10 and 22 vs placebo; HGSS score at Weeks 10 and 22 vs placebo; IGA of scalp hair growth at Weeks 10 and 22; Change from baseline in WAA-QoL total score at Week 22 vs placebo

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Estetra

Sponsor organisation

Estetra

Address

Rue Saint-Georges 5

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Estetra

Contact name

Sigrid Schollen

Public contact point

Organisation

Estetra

Contact name

Sigrid Schollen

Locations

1 EU/EEA country · 1 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 5 files

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

Application history

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