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A Phase 3, Randomized, Placebo-controlled, Double-blind Study to Investigate the Long Term Safety of Fezolinetant in Japanese Women Experiencing Vasomotor Symptoms (Hot Flashes) Associated with Menopause (Starlight 3)

A study to assess long-term safety of fezolinetant given to Japanese women going through menopause (Starlight 3)

Xuegong Wang

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

clinicaltrialregistration@astellas.com

Medical Information Center

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

+81-120-189-371

clinicaltrialregistration@astellas.com

Complete

Feb. 09, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Participant confirmed as menopausal per one of the following criteria at the screening visit (visit 1):
- For a post-menopausal participant:
o Spontaneous amenorrhea for >= 12 consecutive months;
o Spontaneous amenorrhea for >= 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L);
o Having had bilateral oophorectomy >= 6 weeks prior to the screening visit (visit 1) (with or without hysterectomy);
o Having had hysterectomy without bilateral oophorectomy with the biochemical criteria of menopause (FSH > 40 IU/L); or
o Having been confirmed to be post-menopausal in the 2693-CL-0310 study.
- For a peri-menopausal participant:
o Spontaneous amenorrhea for >= 60 days but < 6 consecutive months 2 times in the 2 most recent menstrual cycles with biochemical criteria of peri-menopause (FSH > 25 IU/L); or
o Spontaneous amenorrhea for >= 6 months but < 12 consecutive months with biochemical criteria of peri-menopause (FSH > 25 IU/L and <= 40 IU/L).
o Having had hysterectomy without bilateral oophorectomy with the biochemical criteria of peri-menopause (FSH > 25 IU/L and <= 40 IU/L)
2. Participant is seeking treatment for relief of vasomotor symptoms (VMS) associated with menopause.
3. Female participant:
- Is not pregnant and at least 1 of the following conditions apply:
a. Not a women of childbearing potential (WOCBP)
b. WOCBP who has a negative urine pregnancy test day 1 (visit 2) and agrees to follow the contraceptive guidance from the time of informed consent through at least 21 days after final study intervention administration.
- Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 21 days after final study intervention administration.
- Must not donate ova starting at first administration of study intervention and throughout the investigational period and for 21 days after final study intervention administration.
4. Participant agrees not to participate in another interventional study while participating in the present study.

1. Participant has a history of an undiagnosed uterine bleeding within the 6 months prior to the screening visit (visit 1).
2. Participant has a current malignant tumor or history (except for a participant who has not received treatment for malignant tumors for at least 5 years before informed consent acquisition and was not considered to have recurrence) of a malignant tumor except for non-metastatic basal cell carcinoma of the skin.
3. Participant has a medical condition or chronic disease (including history of neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine, or gynecological disease) that could confound interpretation of the study outcome.
4. Participant uses a prohibited therapy (hormone therapy, hormone replacement therapy [HRT], hormonal contraceptive, any treatment for VMS [prescription medications, over-the-counter, or herbal/Kampo medicines] or strong or moderate cytochrome P450 1A2 [CYP1A2] inhibitors) and is not willing to wash out or discontinue use of such drugs from screening visit (visit 1) through the follow-up visit (visit 16) or it is not medically appropriate to discontinue such drugs for the duration of the study.
5. Participant has been randomized/registered in a clinical trial with fezolinetant previously or had previous exposure to marketed fezolinetant elsewhere.
6. Participant has a present or previous history of participation in this study.
7. Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening visit (visit 1).
8. Participant has an unacceptable result from the transvaginal ultrasound (TVU) assessment at screening (i.e., full length of endometrial cavity cannot be visualized or presence of clinically significant abnormal findings).
9. Participant has documentation of a clinically significant abnormal Papanicolaou (Pap) test (or equivalent cervical cytology) within 12 months prior to the screening visit (visit 1) or at screening.
10. Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total bilirubin (TBL) or direct bilirubin (DBL), elevated international normalized ratio (INR), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to < 1.5 x upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant with mildly elevated ALP (up to < 1.5 x ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
11. Participant has creatinine > 1.5 x ULN or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula <= 30 mL/min/1.73 m^2 at screening.
12. Participant has positive hepatitis serology panel (i.e., positive hepatitis B surface [HBs] antigen and/or positive hepatitis C virus [HCV] antibody) at screening. If HCV antibody test result is equivocal, hepatitis C virus ribonucleic acid (HCV RNA) test at study site is allowed. Participant can be enrolled if that result is normal or not abnormal.
13. Participant is not in good general health as determined on the basis of medical history and general physical examination performed at the screening; hematology parameters, biochemistry parameters, pulse rate, blood pressure, electrocardiogram (ECG) outside the reference range for the population studied, or is showing clinically relevant deviations.
14. Participant has a history of suicide attempt or suicidal behavior within 12 months prior to study enrollment or suicidal ideation within 12 months prior to study enrollment (a response of "yes" to question 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale [C-SSRS]), or is at significant risk to commit suicide at day 1 (visit 2).
15. Participant is unable or unwilling to complete the study procedures.
16. Participant has any condition which makes the participant unsuitable for study participation.
17. Participant has a known or suspected hypersensitivity to fezolinetant or any components of the formulation used.
18. Participant is the investigator or a member of the study site staff.
19. Participant is an employee of Astellas, the study-related contract research organizations (CROs) or site management organizations.

Hot Flashes

The women will take 1 tablet of the study medicine (fezolinetant or the placebo) once a day for up to 52 weeks.
During the study, the women will visit their study clinic for a check-up about every 4 weeks for up to 52 weeks (1 year). At each visit they will be asked if they had any medical problems. Other checks will include a medical examination and vital signs (temperature, blood pressure and pulse). At some visits, the women will have an ECG to check their heart rhythm and some blood and urine samples will be taken for laboratory tests. During a couple of visits, women who have a womb (uterus) will also have a test called a transvaginal ultrasound. A probe is gently placed inside the vagina. Sound waves will create a picture of the organs in the pelvis. This will allow the study doctor to look more closely at the uterus and surrounding organs.
The last clinic visit will be 3 weeks after the women take their final tablet of the study medicine (fezolinetant or the placebo).

Frequency and severity of Adverse Events (AEs)

o Mean change from baseline in endometrial thickness at 52 weeks in post menopausal participants
o Clinical laboratory tests: hematology, coagulation, biochemistry, liver biochemistry and urinalysis
o Vital signs: body temperature, sitting systolic and diastolic blood pressure and pulse rate
o ECG parameters
o Plasma concentrations of fezolinetant and metabolite ES259564 at scheduled time points

+81-3-6779-8166

Jan. 25, 2024

Yes

Access to anonymized individual participant level data collected during the study, in addition to supporting clinical documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/. Study-related supporting documentation is redacted and provided if available, such as the protocol and amendments, statistical analysis plan and clinical study report. Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data. Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

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