A Study to Assess the Safety and Tolerability of Fezolinetant in Women Seeking Treatment for Relief of Vasomotor Symptoms (VMS) Associated With Menopause

Hot Flashes Clinical Trial

— Moonlight 3  

Official title:

A Single-Arm Phase 3 Clinical Study to Investigate the Long-Term Safety of Fezolinetant in Women in China Suffering From Vasomotor Symptoms (Hot Flashes) Associated With Menopause

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04451226
• Other study ID #: 2693-CL-0307
• Secondary ID: CTR20200676
• Status: Completed
• Phase: Phase 3
• Start date: July 30, 2020
• Est. completion date: June 13, 2022

Study information

• Verified date: September 2023
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is for women in menopause with hot flashes. Menopause, a normal part of aging, is the time of a woman's last period. Hot flashes can interrupt a woman's daily life. The purpose of this study is to find out how safe it is for these women to take fezolinetant long term (up to 52 weeks). To do that, the study will look at the number and severity of the "adverse events." Those are the side effects that study participants have while they are in the study. The study treatment is fezolinetant (1 tablet of fezolinetant) once a day. The study participants will take study treatment for 52 weeks. At weeks 2 and 4 and then once a month, the study participants will go the hospital or clinic for a check-up. They will be asked about medications, side effects and how they feel. Other checks will include physical exam and vital signs (heart rate, temperature and blood pressure). Blood and urine will be collected for laboratory tests. At some study visits, study participants will complete questionnaires that are about their quality of life. Study participants who still have their uterus will have 2 more tests done at the first and last study visits. One of the 2 tests is endometrial biopsy. This test involves removing a small amount of tissue from the inside lining of the uterus. The tissue is then checked under a microscope. The other test is transvaginal ultrasound. It uses sound waves to create pictures of the organs in the pelvis. The sound waves are transmitted by a probe (transducer), which is placed inside the vagina. Study participants may have a screening mammogram done at the first and/or last study visit. A mammogram is an x-ray picture of the breasts used to screen for breast cancer. Study participants who did not have this test done in the last 12 months will have it done at the first study visit. They will have it done at the last study visit if they are due for their screening mammogram and their own doctor agrees. The last check-up at the hospital or clinic will be 3 weeks after the last dose of study treatment.

Description:

The study will consist of a screening period, a 52-week treatment period and a follow-up visit, 3 weeks after the last dose of study drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: June 13, 2022
• Est. primary completion date: June 13, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subject has a body mass index = 16 kg/m^2 and = 38 kg/m^2 at the screening visit.

• Subject confirmed as menopausal per 1 of the following criteria at the screening visit:

O Subject has spontaneous amenorrhea for >= 12 consecutive months O Spontaneous amenorrhea for = 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 International Units per Liter [IU/L], or O Having had bilateral oophorectomy = 6 weeks prior to the screening visit (with or without hysterectomy).

O FSH > 40 IU/L if subjects received hysterectomy but still have ovary

• Subject is seeking treatment for relief for VMS associated with menopause.

• Subject is in good general health as determined on the basis of medical history and general physical examination, including a bimanual clinical pelvic examination and clinical breast examination devoid of relevant clinical findings, performed at the screening visit; hematology and biochemistry parameters; pulse rate and/or blood pressure; and ECG within the reference range for the population studied, or showing no clinically relevant deviations.

• Subject has documentation of a normal/negative or no clinically significant abnormal findings on mammogram (or echo) (e.g., <BI-RADS class 4; obtained at screening or within the prior 12 months of screening). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant abnormal findings.

• Subject is willing to undergo a transvaginal ultrasound (TVU) to evaluate the uterus and ovaries at screening and at week 52 (end of treatment). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit. This is not required for subjects who have had a partial (supra-cervical) or full hysterectomy.

• Subject is willing to undergo an endometrial biopsy at screening and at week 52 (end of treatment) or the ED visit if endometrial thickness > 4 millimeter (mm) indicated by TVU; and subject is willing to undergo an endometrial biopsy at any time during the study in the case of uterine bleeding. This is not required for subjects who have had a partial (supra-cervical) or full hysterectomy. A biopsy with insufficient material for evaluation, or unevaluable material, is acceptable provided the endometrial thickness is no greater than 8 mm.

• Subject has documentation of a normal or not clinically significant abnormal Papanicolaou (Pap) test (or equivalent cervical cytology) within the previous 12 months of screening or at screening. This is not required for subjects who have had a full hysterectomy.

• Subject has a negative urine pregnancy test at screening.

• Subject has a negative serology panel (including hepatitis B virus surface antigen [HBs] and hepatitis C virus antibody [anti-HCV], and human immunodeficiency virus [HIV]) at screening.

• Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

• Subject uses a prohibited therapy (strong and moderate cytochrome P450 [CYP] 1A2 inhibitors, hormone replacement therapy [HRT], hormonal contraceptive, any treatment for VMS [prescription, over the counter or herbal]) or is not willing to wash out and discontinue such drugs for the full extent of the study.

• Subject has a known substance abuse or alcohol addiction within 6 months of screening.

• Subject has a history of a malignant tumor, except for non-metastatic basal cell carcinoma of the skin.

• Subject has uncontrolled hypertension, defined as systolic blood pressure >= 140 millimeters of mercury (mmHg) or diastolic blood pressure as >= 90 mmHg based on an average of 2 to 3 readings within the screening period.

O Subjects with a medical history of hypertension who are well controlled may be enrolled.

O Subjects who do not meet the criteria may, be re-assessed after initiation or review of antihypertensive measures.

• Subject has a history of severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients.

• For subjects with a uterus: Subject has an unacceptable result from the TVU assessment at screening, i.e., full length of endometrial cavity cannot be visualized or presence of a clinically significant abnormal finding.

• For subjects with an endometrial thickness > 4 mm as indicated by TVU at screening:

Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyperplasia, endometrial cancer, or other clinically significant abnormal findings in the at screening. A biopsy with insufficient material for evaluation, or unevaluable material is acceptable provided the endometrial thickness is no greater than 8 mm.

• Subject has a history of an undiagnosed uterine bleeding within the last 6 months of screening.

• Subject has a history of seizures or other convulsive disorders.

• Subject 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) or malignancy that could confound interpretation of the study outcome.

• Subject has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]), elevated total or direct bilirubin, elevated international normalized ratio (INR), or elevated alkaline phosphatase (ALP) at screening. Subject with mildly elevated ALT or AST up to 1.5 × the upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Subject with mildly elevated ALP (up to 1.5 × ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Subject with Gilbert's syndrome with elevated total bilirubin (TBL) may be enrolled as long as hemolysis is ruled out (i.e., direct bilirubin (DBL), hemoglobin and reticulocytes are normal).

• Subject has creatinine > 1.5 × ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula <= 59 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at the screening visit.

• Subject has a history of suicide attempt or suicidal behavior within the prior to 12 months of study enrollment or has suicidal ideation within the prior to 12 months of study enrollment (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the C-SSRS), or who is at significant risk to commit suicide at screening and at visit 2.

• Subject has previously been enrolled in a clinical trial with fezolinetant.

• Subject has received an investigational study drug within 28 days or 5 half-lives, whichever is longer, prior to screening.

• Subject is unable or unwilling to complete the study procedures.

• Subject has any condition which, makes the subject unsuitable for study participation.

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• Fezolinetant
Oral

Locations

Country	Name	City	State
China	Site CN86002	Beijing
China	Site CN86015	Beijing
China	Site CN86029	Beijing
China	Site CN86032	Chengdu
China	Site CN86001	Guangzhou
China	Site CN86019	Guangzhou
China	Site CN86022	Guangzhou
China	Site CN86040	Guangzhou
China	Site CN86042	Guangzhou
China	Site CN86008	Hangzhou
China	Site CN86012	Hangzhou
China	Site CN86005	Hunan
China	Site CN86039	Jiangsu
China	Site CN86010	Jinlin
China	Site CN86020	Kunming
China	Site CN86037	Liuzhou
China	Site CN86006	Nanjing
China	Site CN86007	Nanjing
China	Site CN86018	Nanning
China	Site CN86034	Ningxia Hui Nationality Autonomous Region
China	Site CN86009	Shanghai
China	Site CN86011	Shanxi
China	Site CN86004	Shenzhen
China	Site CN86028	Shijiazhuang
China	Site CN86026	Suzhou
China	Site CN86038	Taiyuan
China	Site CN86030	Tianjin
China	Site CN86036	Tianjin
China	Site CN86025	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma China, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.	Up to 55 weeks
Primary	Number of Participants With Adverse Events Based on Severity	An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.	Up to 55 weeks
Secondary	Change From Baseline in Endometrial Thickness	Endometrial thickness is a measure of how thick the lining of the uterus is. Change from baseline will be reported.	Baseline and 52 weeks
Secondary	Percentage of Participants With Endometrial Hyperplasia and/or Endometrial Cancer	Endometrial hyperplasia is thickening of the lining of the uterus. Endometrial cancer is cancer of the lining of the uterus. Percentage of participants will be reported.	Up to 52 weeks
Secondary	Number of Participants With Vital Sign Abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to 55 weeks
Secondary	Number of Participants With Laboratory Value Abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to 55 weeks
Secondary	Number of Participants With Suicidal Ideation and/or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) will be reported.	Up to 55 weeks
Secondary	Number of Participants With Electrocardiogram (ECG) Abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant ECG values.	Up to 52 weeks
Secondary	Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) Levels	Change from baseline in serum concentrations of BSAP will be reported.	Baseline, week 52 and week 55
Secondary	Change From Baseline in Procollagen Type 1 Amino-terminal Propeptide (P1NP) Levels	Change from baseline in serum concentrations of P1NP will be reported.	Baseline, week 52 and week 55
Secondary	Change From Baseline in Carboxy-terminal Telopeptide of Type I Collagen (CTX) Levels	Change from baseline in serum concentrations of CTX will be reported.	Baseline, week 52 and week 55
Secondary	Change From Baseline in Serum Concentration of Sex Hormones	Change from baseline in serum concentration of sex hormones will be reported.	Baseline, week 4, week 12, week 24 , week 52 and week 55
Secondary	Change From Baseline in Sex Hormone-Binding Globulin (SHBG)	Change from baseline in serum concentration of SHBG will be reported.	Baseline, week 4, week 12, week 24 , week 52 and week 55
Secondary	Pharmacokinetics (PK) of Fezolinetant in Plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Week 4, week 12, week 24 and week 52
Secondary	Pharmacokinetics (PK) of Fezolinetant Metabolite ES259564 in Plasma: Concentration	Concentration will be recorded from the PK plasma samples collected.	Week 4, week 12, week 24 and week 52

External Links

•   Link Description: Link to plain language summary of the study on the Trial Results Summaries website.
•   Link Description: Link to results and other applicable study documents on the Astellas Clinical Trials website.