Phase 2 Randomized, Double-Blind, Placebo-Controlled Study on Estetrol Monohydrate's Effect on Hair Growth in Postmenopausal Women with Female Pattern Hair Loss
- Trial ID
- 2024-517890-26-00
- Sponsor
- Estetra
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of treatment with estetrol (E4) 20 mg compared to placebo on hair growth parameters in postmenopausal women with female pattern hair loss. This will be assessed through quantitative hair measurement, specifically the Target Area Hair Count (TAHC) of non-vellus hair and Target Area Hair Width (TAHW) at week 22. Additionally, the study aims to evaluate the general **safety** of E4 treatment, its effect on the endometrium in non-hysterectomized subjects, and the frequency of vaginal bleeding in these subjects compared to placebo. These objectives are clinically relevant as they address both the potential therapeutic benefits and safety profile of E4 in managing hair loss and associated symptoms in postmenopausal women.
Secondary objectives include assessing the influence of E4 treatment on additional hair parameters:
- Quantitative hair measurement of TAHC of non-vellus hair at week 10
- Quantitative hair measurement of TAHC of vellus/miniaturized hair at weeks 10 and 22
- Quantitative hair measurement of TAHW at week 10
- Subjective Scalp Assessment (SSA) of scalp hair growth using Hair Growth Assessment (HGA), Hair Growth Index (HGI), and Hair Growth Satisfaction Scale (HGSS) at weeks 10 and 22
- Investigator Global Assessment (IGA) of scalp hair growth at weeks 10 and 22
Participants
The clinical trial involves a study population of **postmenopausal women** aged between 40 and 65 years, experiencing **vasomotor menopausal symptoms**. The trial exclusively includes female participants, with no male or vulnerable populations involved. Participants are required to be in good physical and mental health, as determined by the investigator through medical history, physical and gynecological examinations, and clinical assessments. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are expected to maintain consistent lifestyle habits, including their dietary and supplement patterns, as well as their hair care regimen, throughout the study. Key inclusion criteria include a body mass index (BMI) between 18.5 kg/m² and 35.0 kg/m², and a mammogram showing no significant disease. Participants must also demonstrate a decrease in hair density on the top of the scalp, relative to the sides and back, and agree to maintain the same hairstyle, hair length, and hair color during the trial period.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled, Phase 2 study** designed to evaluate the efficacy and safety of estetrol monohydrate (E4) in postmenopausal women with female pattern hair loss. The primary objective is to assess the influence of E4 20 mg on hair growth parameters, specifically the Target Area Hair Count (TAHC) and Target Area Hair Width (TAHW), over a 6-month period. The trial will also evaluate the general safety of E4 treatment, its effect on the endometrium in non-hysterectomized subjects, and the frequency of vaginal bleeding.
The trial will involve a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, postmenopausal status, and health condition. Participants will be required to sign an informed consent form before any study procedures commence. Following randomization, participants will attend follow-up visits at specified intervals to monitor treatment effects and safety. The end-of-study visit will occur at the conclusion of the 6-month treatment period, where final assessments will be conducted.
Participants are expected to be involved in the study for approximately 24 weeks, with the possibility of early termination if they experience significant adverse events or fail to comply with study protocols. The trial will utilize a film-coated tablet formulation of E4, administered orally, with a maximum daily dose of 20 mg. The placebo will be a film-coated tablet designed to match the active treatment. The study aims to provide valuable insights into the potential therapeutic benefits of E4 for hair growth in the target population.
Treatment
The clinical trial involves the administration of **estetrol monohydrate**, a chemical compound, as the experimental medication. The investigational product is provided in the form of a film-coated tablet, with each tablet containing 20 mg of estetrol monohydrate. The route of administration is oral, and the dosing schedule involves a daily intake of one tablet, resulting in a maximum daily dose of 20 mg. The total treatment period extends up to 24 weeks, with a cumulative maximum dose of 3360 mg. Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.
The study also includes a **placebo** group, which receives a film-coated tablet designed to match the estetrol monohydrate tablet in appearance but contains no active substance. The placebo is administered orally, following the same dosing schedule as the experimental medication, with one tablet taken daily. This placebo control is essential for maintaining the double-blind nature of the trial, allowing for an unbiased assessment of the efficacy and safety of estetrol monohydrate in comparison to the placebo. Participant compliance with the placebo regimen is similarly monitored to ensure the integrity of the study data.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the influence of treatment with estetrol monohydrate (E4) 20 mg compared to placebo on hair growth parameters in postmenopausal women with female pattern hair loss. The primary efficacy endpoints include the change from baseline in Target Area Hair Count (TAHC) and Target Area Hair Width (TAHW) of non-vellus hair at Week 22. Secondary endpoints involve changes from baseline in TAHC and TAHW at Week 10, as well as Hair Growth Assessment (HGA) scores, Hair Growth Index (HGI), and Hair Growth Satisfaction Scale (HGSS) scores at Weeks 10 and 22. Additionally, Investigator Global Assessment (IGA) of scalp hair growth and changes in Women's Androgenetic Alopecia Quality of Life (WAA-QoL) total score at Week 22 will be measured.
Quantitative hair measurements will be conducted using validated methods to ensure accuracy and reliability. The assessments will be performed at specified time points, including Weeks 10 and 22, to monitor the progression and efficacy of the treatment. The data collected will be analyzed to determine the statistical significance of the changes observed in the treatment group compared to the placebo group. This structured approach will provide a comprehensive evaluation of the efficacy of estetrol monohydrate in improving hair growth parameters in the target population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 06 Oct 2023 | 60 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Film-coated placebo to match estetrol monohydrate (E4) 20mg tablet | Placebo | N/A | — | — | — | N/A |