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A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause (Skylight 4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04003389
Recruitment Status : Recruiting
First Posted : July 1, 2019
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE July 1, 2019
Last Update Posted Date October 14, 2020
Actual Study Start Date  ICMJE July 10, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2020)
  • Frequency of Adverse Events (AE) [ Time Frame: Up to 55 weeks ]
    An AE is any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
  • Severity of Adverse Events [ Time Frame: Up to 55 weeks ]
    An AE is any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
  • Percentage of participants with endometrial hyperplasia and/or endometrial cancer [ Time Frame: Up to 52 weeks ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Frequency of Adverse Events (AE) [ Time Frame: Up to 55 weeks ]
    An AE is any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
  • Severity of Adverse Events [ Time Frame: Up to 55 weeks ]
    An AE is any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2020)
  • Change from baseline in endometrial thickness [ Time Frame: Baseline and 52 weeks ]
    Endometrial thickness is a measure of how thick the lining of the uterus is. Change from baseline will be reported.
  • Change from baseline in bone mass density (BMD) at hip [ Time Frame: Baseline and 52 weeks ]
    Bone density is the amount of bone mineral in bone tissue. The change from baseline will be reported.
  • Change from baseline in trabecular bone score (TBS) at hip [ Time Frame: Baseline and 52 weeks ]
    The trabecular bone score is a measure of bone texture correlated with bone microarchitecture. High TBS value means that microarchitecture bone is dense, well connected with little spaces between trabeculaes. Low TBS value means that the microarchitecture of bone is incomplete and poorly connected with wide spaces between trabeculae. Change from baseline will be reported.
  • Change from baseline in bone mass density (BMD) at spine [ Time Frame: Baseline and 52 weeks ]
    Bone density is the amount of bone mineral in bone tissue. Change from baseline will be reported.
  • Change from baseline in trabecular bone score (TBS) at spine [ Time Frame: Baseline and 52 weeks ]
    The trabecular bone score is a measure of bone texture correlated with bone microarchitecture. High TBS value means that microarchitecture bone is dense, well connected with little spaces between trabeculaes. Low TBS value means that the microarchitecture of bone is incomplete and poorly connected with wide spaces between trabeculae. Change from baseline will be reported.
  • Number of participants with vital sign abnormalities and /or adverse events (AEs) [ Time Frame: Up to 55 weeks ]
    Number of participants with potentially clinically significant vital sign values.
  • Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 55 weeks ]
    Number of participants with potentially clinically significant laboratory values.
  • Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs) [ Time Frame: Up to 52 weeks ]
    Number of participants with potentially clinically significant ECG values.
  • Number of participants with suicidal ideation and/or behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 55 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Change from baseline in endometrial thickness [ Time Frame: Baseline and 52 weeks ]
    Endometrial thickness is a measure of how thick the lining of the uterus is. Change from baseline will be reported.
  • Percentage of participants with endometrial hyperplasia and/or endometrial cancer [ Time Frame: Up to 52 weeks ]
    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.
  • Change from baseline in bone mass density (BMD) at hip [ Time Frame: Baseline and 52 weeks ]
    Bone density is the amount of bone mineral in bone tissue. The change from baseline will be reported.
  • Change from baseline in trabecular bone score (TBS) at hip [ Time Frame: Baseline and 52 weeks ]
    The trabecular bone score is a measure of bone texture correlated with bone microarchitecture. High TBS value means that microarchitecture bone is dense, well connected with little spaces between trabeculaes. Low TBS value means that the microarchitecture of bone is incomplete and poorly connected with wide spaces between trabeculae. Change from baseline will be reported.
  • Change from baseline in bone mass density (BMD) at spine [ Time Frame: Baseline and 52 weeks ]
    Bone density is the amount of bone mineral in bone tissue. Change from baseline will be reported.
  • Change from baseline in trabecular bone score (TBS) at spine [ Time Frame: Baseline and 52 weeks ]
    The trabecular bone score is a measure of bone texture correlated with bone microarchitecture. High TBS value means that microarchitecture bone is dense, well connected with little spaces between trabeculaes. Low TBS value means that the microarchitecture of bone is incomplete and poorly connected with wide spaces between trabeculae. Change from baseline will be reported.
  • Number of participants with vital sign abnormalities and /or adverse events (AEs) [ Time Frame: Up to 55 weeks ]
    Number of participants with potentially clinically significant vital sign values.
  • Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 55 weeks ]
    Number of participants with potentially clinically significant laboratory values.
  • Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs) [ Time Frame: Up to 52 weeks ]
    Number of participants with potentially clinically significant ECG values.
  • Number of participants with suicidal ideation and/or behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 55 weeks ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause
Official Title  ICMJE A Randomized, Placebo-Controlled, Double-Blind Phase 3 Clinical Study to Investigate the Long-Term Safety of Fezolinetant in Women Suffering From Vasomotor Symptoms (Hot Flashes) Associated With Menopause
Brief 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 treatments are fezolinetant low dose (1 tablet of fezolinetant and 1 placebo tablet) once a day, fezolinetant high dose (2 tablets of fezolinetant) once a day or placebo (2 tablets) once a day. (Placebo is a dummy treatment that looks like medicine but does not have any medicine in it.) Women in this study will be picked for 1 of the 3 study treatments by chance alone. The study participants will take study treatment for 52 weeks.

This study is "double-blinded." That means that the study participants and the study doctors do not know who takes which of the study treatments (fezolinetant low dose, fezolinetant high dose or placebo).

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. At the first and last study visits, they will have a dual-energy x-ray absorptiometry (DXA for short) test done. To measure bone loss in the hips and spine, DXA creates pictures of the inside of these areas with low-dose x-rays. (The dose is approximately one-tenth of the amount of a normal chest x-ray.) 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.

Detailed Description This study will consist of a screening period and a 52 week treatment period. Safety follow up will occur 3 weeks after the last dose of study drug.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hot Flashes
Intervention  ICMJE
  • Drug: fezolinetant
    administered orally
  • Drug: placebo
    administered orally
Study Arms  ICMJE
  • Experimental: low dose fezolinetant
    Participants will receive low dose fezolinetant for 52 weeks.
    Intervention: Drug: fezolinetant
  • Experimental: high dose fezolinetant
    Participants will receive high dose fezolinetant for 52 weeks.
    Intervention: Drug: fezolinetant
  • Placebo Comparator: placebo
    Participants will receive placebo for 52 weeks.
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 14, 2020)
1740
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2019)
1149
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject has a body mass index ≥ 18 kg/m^2 and ≤ 38 kg/m^2.
  • Subject must be seeking treatment or relief for vasomotor symptoms (VMS) associated with menopause and confirmed as menopausal per 1 of the following criteria at the screening visit:

    • Spontaneous amenorrhea for ≥ 12 consecutive months
    • Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (follicle stimulating hormone > 40 IU/L), or
    • Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit.
  • 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 mammogram findings (obtained at screening or within the prior 12 months of study enrollment). Appropriate documentation includes a written report or an electronic report indicating normal/negative or no clinically significant mammographic 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 (EOT). For subjects who are withdrawn from the study prior to completion, a TVU should be collected at the early discontinuation (ED) visit.
  • Subject is willing to undergo an endometrial biopsy at screening and at week 52 (EOT) or the ED visit for subjects who are withdrawn from the study prior to completion, and any time during the study in the case of uterine bleeding. The endometrial biopsy obtained at screening must be considered evaluable.
  • Subject has documentation of a normal or not clinically significant Papanicolaou (Pap) test (or equivalent cervical cytology) within the previous 12 months or at screening.
  • Subject has a negative urine pregnancy test at screening.
  • Subject has a negative serology panel (i.e., negative hepatitis B surface antigen, negative hepatitis C virus antibody and negative human immunodeficiency virus antibody screens) 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 or 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 previous or current history of a malignant tumor, except for basal cell carcinoma.
  • Subject's systolic blood pressure is ≥ 130 mmHg or diastolic blood pressure is ≥ 80 mmHg based on the average of 2 to 3 readings, on at least 2 different occasions within the screening period.

    • Subjects who do not meet these criteria may be re-assessed after initiation or review of antihypertensive measures.
    • Subjects with a medical history of hypertension can be enrolled once they are medically clear (stable and compliant).
  • Subject has a history of severe allergy, hypersensitivity or intolerance to drugs in general, including the study drug and any of its excipients.
  • 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 finding.
  • Subject has an endometrial biopsy confirming presence of disordered proliferative endometrium, endometrial hyperplasia, endometrial cancer, or other clinically significant findings at screening.
  • Subject has a history within the last 6 months of undiagnosed uterine bleeding.
  • 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). Patients with mildly elevated ALT or AST up to 1.5 times the upper limit of normal (ULN) can be enrolled if total and direct bilirubin are normal. Patients 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. Patients with Gilbert's syndrome with elevated total bilirubin may be enrolled as long as direct bilirubin, hemoglobin and reticulocytes are normal.
  • Subject has creatinine > 1.5 x ULN; or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula ≤ 59 mL/min per 1.73 m^2 at the screening visit.
  • Subject has a history of suicide attempt or suicidal behavior within the last 12 months or has suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale [C-SSRS]), or who is at significant risk to commit suicide, as assessed at screening and at the time of visit 2 (randomization).
  • Subject has previously been enrolled in a clinical trial with fezolinetant.
  • Subject is participating concurrently in another interventional study or participated in an interventional study within 28 days prior to screening, or received any investigational drug within 28 days or within 5 half-lives prior to screening, whichever is longer.
  • Subject is unable or unwilling to complete the study procedures.
  • Subject has any condition which makes the subject unsuitable for study participation.
  • Subject has had a partial or full hysterectomy.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 40 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Astellas Pharma Global Development 800-888-7704 astellas.registration@astellas.com
Listed Location Countries  ICMJE Canada,   Czechia,   Latvia,   Poland,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04003389
Other Study ID Numbers  ICMJE 2693-CL-0304
2019-000275-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds 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. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 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
Access Criteria: 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.
URL: https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP