FEZOLINETANT for Vasomotor symptoms (hot flashes) | Hormone receptor-positive breast cancer

Inclusion criteria

• {"criterion_text":"- Participant is born female, and at least 18 years of age at the time of signing the informed consent form (ICF)."}
• {"criterion_text":"- Participant has a personal history of stage 0-3 HR+, either human epidermal growth factor receptor-2 postitive (HER-2+) or HER-2 negative (HER-2-) breast cancer; appropriate documentation includes a written or electronic report."}
• {"criterion_text":"- Participant must be receiving stable maintenance adjuvant endocrine therapy (e.g., tamoxifen or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months prior to randomization and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. If the participant is taking GnRH agonists/antagonists, therapy must also be stable for a minimum of 4 months prior to randomization. Add-on therapies for breast cancer adjuvant treatment (e.g., cyclin-dependent kinase (CDK)-4 inhibitors) are allowed."}
• {"criterion_text":"- Participant has a minimum average of 7 moderate to severe VMS per day as recorded in the electronic daily diary (data must be available for at least 7 of the last 10 days prior to randomization)."}
• {"criterion_text":"- Has an Eastern Cooperative Oncology Group (ECOG) score 0 or 1."}
• {"criterion_text":"- Has at least 12-month life expectation."}
• {"criterion_text":"- Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunnodeficiency virus (HIV) antibody screens)."}

Exclusion criteria

• {"criterion_text":"- Participant has diagnosis of metastatic breast cancer (stage 4)."}
• {"criterion_text":"- Participant has current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy except for HR+ breast cancer (stage 0 to 3) or basal cell carcinoma."}
• {"criterion_text":"- Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent."}
• {"criterion_text":"- Participant has active liver disease, jaundice, or elevated liver alanine or aspartate aminotransferases (ALT or AST), elevated total bilirubin (TBL) or direct bilirubin (DBL) or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to < 2 × upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant 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. Participant with Gilbert’s syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal."}
• {"criterion_text":"- Participant has creatinine > 1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula < 30 mL/min/1.73 m^2 at the screening visit."}
• {"criterion_text":"- Participant has a history of endometrial hyperplasia (participant can be enrolled if she has undergone a hysterectomy) or uterine/endometrial cancer."}
• {"criterion_text":"- 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) or malignancy that could confound interpretation of the study outcome."}
• {"criterion_text":"- Participant uses a prohibited therapy (menopause hormone therapy (MHT), estradiol-containing hormonal contraceptive progestin and progesterone-only medicines, any treatment for VMS [prescription medications, over-the-counter, or herbal] or Cytochrome P450 (CYP)1A2 inhibitors) or is not willing to wash out such drugs; in addition, investigators should consider medications that are contraindicated due to underlying breast cancer diagnosis and the adjuvant endocrine therapy."}
• {"criterion_text":"- Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvant endocrine therapy being used, or any components of the formulations used."}

Primary endpoints

• {"endpoint_text":"- Co-primary endpoints: effect of fezolinetant on the following 4 co-primary variables: Change in the frequency of moderate to severe VMS from baseline (BL) to week 4;","definition_or_measurement_approach":"Change from baseline to week 4 in frequency of moderate to severe VMS measured using electronic daily diary (participant-reported)."}
• {"endpoint_text":"- Change in the frequency of moderate to severe VMS from BL to week 12;","definition_or_measurement_approach":"Change from baseline to week 12 in frequency of moderate to severe VMS measured using electronic daily diary (participant-reported)."}
• {"endpoint_text":"- Change in the severity of moderate to severe VMS from BL to week 4;","definition_or_measurement_approach":"Change from baseline to week 4 in severity of moderate to severe VMS measured using electronic daily diary (participant-reported severity ratings)."}
• {"endpoint_text":"- Change in the severity of moderate to severe VMS from BL to week 12.","definition_or_measurement_approach":"Change from baseline to week 12 in severity of moderate to severe VMS measured using electronic daily diary (participant-reported severity ratings)."}

Secondary endpoints

• {"endpoint_text":"- Change in the Menopause-specific Quality of Life Questionnaire (MENQOL) VMS domain score from BL to week 12; Change in the Patient-reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b Total (raw) Score from BL to week 12.","definition_or_measurement_approach":"MENQOL VMS domain and PROMIS SD SF 8b total (raw) score changes from baseline to week 12 using validated patient-reported outcome instruments."}
• {"endpoint_text":"- Change in the frequency of moderate to severe VMS from BL to week 24; Change in the severity of moderate to severe VMS from BL to week 24.","definition_or_measurement_approach":"Change from baseline to week 24 in frequency and severity of moderate to severe VMS measured by electronic daily diary."}
• {"endpoint_text":"- Incidence and severity of treatment-emergent adverse events (TEAEs) including adverse events of special interest (AESIs), clinical laboratory assessments, vital signs and ECG.","definition_or_measurement_approach":"Safety assessed by recording TEAEs/AESIs, labs, vital signs and ECG per standard clinical trial safety monitoring."}
• {"endpoint_text":"- Change in the frequency of moderate to severe VMS from BL to weeks 1 to 3 and from BL to weeks 5 to 11; Change in the severity of moderate to severe VMS from BL to weeks 1 to 3 and from BL to weeks 5 to 11.","definition_or_measurement_approach":"Shorter-interval changes in frequency and severity measured via electronic daily diary for specified week windows."}
• {"endpoint_text":"- Percent reduction of ≥ 50%, ≥ 75% and 100% in the frequency of moderate to severe VMS from BL to weeks 1, 4, 8 and 12.","definition_or_measurement_approach":"Responder analyses based on percent reductions in daily VMS frequency from baseline at specified timepoints using e-diary."}
• {"endpoint_text":"- Model-based steady-state population PK parameters for fezolinetant (CL/F, Vc/F) and derived exposure-measures of fezolinetant (Cavg and/or Ctrough) with tamoxifen or aromatase inhibitors.","definition_or_measurement_approach":"Population PK modelling to derive CL/F, Vc/F and exposure measures (Cavg/Ctrough) for fezolinetant when co-administered with tamoxifen or aromatase inhibitors."}
• {"endpoint_text":"- Model-based steady-state population PK parameters for tamoxifen and its metabolites (4-OH tamoxifen, N-desmethyltamoxifen and endoxifen) and aromatase inhibitors (CL/F, Vc/F) and derived exposure-measures (Cavg and/or Ctrough) with and without fezolinetant co-administration.","definition_or_measurement_approach":"Population PK modelling for tamoxifen, metabolites and aromatase inhibitors with and without fezolinetant co-administration to assess interactions."}
• {"endpoint_text":"- 8a. Change in the MENQOL Total Score from BL to weeks 4, 8, 12 and 24; Change in the MENQOL domain scores from BL to weeks 4, 8, 12 and 24;","definition_or_measurement_approach":"MENQOL total and domain score changes from baseline at specified weeks using the validated MENQOL instrument."}
• {"endpoint_text":"- 8b. Change in the PROMIS SD SF 8b Total (raw) Score from BL to weeks 4, 8, 12 and 24;","definition_or_measurement_approach":"PROMIS SD SF 8b total (raw) score change from baseline at specified weeks using validated instrument."}
• {"endpoint_text":"- 8c. Scores on the Patient Global Impression of Change (PGI-C) VMS at weeks 4, 8, 12 and 24; Change in the Patient Global Impression of Severity (PGI-S) VMS Score from BL to weeks 4, 8, 12 and 24;","definition_or_measurement_approach":"PGI-C and PGI-S VMS scores and change from baseline at specified weeks (patient global assessments)."}
• {"endpoint_text":"- 8d. Scores on the PGI-C sleep disturbance (SD) at weeks 4, 8, 12 and 24; Change in the PGI-S SD Score from BL to weeks 4, 8, 12 and 24.","definition_or_measurement_approach":"PGI-C and PGI-S sleep disturbance scores at specified weeks and change from baseline."}
• {"endpoint_text":"- 8e PGI-S SD response (at least 2 levels of improvement from BL) at weeks 4, 8, 12 and 24.","definition_or_measurement_approach":"Responder analysis defined as >=2-level improvement on PGI-S SD from baseline at specified weeks."}

Methods

• Patient outreach letters (K2 Patient Outreach/Patient Letter) targeted to potential participants
• Flyers, study posters and brochures distributed at sites
• Print advertisements
• Appointment-reminder cards and inclusion/exclusion cards for site use
• Referring-physician letters and site-kit letters for clinician referral
• Informed-consent flipbooks and participant-facing materials provided at sites
• Digital patient-facing landing pages and eConsent materials (electronic consent screens, screenshots, security/privacy quick reference guides)
• Electronic daily diary (for eligibility and endpoint collection) and digital recruitment materials

Spain

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

453

Number Of Participants

29

Netherlands

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

465

Number Of Participants

85

Denmark

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

455

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

09-12-2025

Processing Time Days

442

Number Of Participants

77

Italy

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

446

Number Of Participants

46

Germany

Earliest CTIS Part Ii Submission Date

19-09-2024

Latest Decision Or Authorization Date

11-12-2025

Processing Time Days

448

Number Of Participants

39

France

Earliest CTIS Part Ii Submission Date

19-09-2024

Latest Decision Or Authorization Date

07-01-2026

Processing Time Days

475

Number Of Participants

25

Hungary

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

502

Number Of Participants

20

Czechia

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

516

Number Of Participants

53

Primary sponsor

Full Name

Astellas Pharma Global Development Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pharmaceutical Product Development LLC

Responsibilities

code 4

Name

Icon Clinical Research Limited

Responsibilities

codes 1, 2, 5

Name

IQVIA Limited

Responsibilities

Electronic Informed Consent; code 3

Name

Medidata Solutions Inc.

Responsibilities

code 7

Name

Syneos Health Clinique Inc.

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties code: 15 (DXA imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"SGS Belgium","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1, 2, 5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 15 (Electronic Informed Consent), 3","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Marken Limited","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Pharmaceutical company"}