A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women with Breast Cancer Who Are Having Hormone Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

24 Jan 2025 → ongoing

Decision date (initial)

2024-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astellas Pharma Global Development, Inc.

External identifiers

EU CT number

2024-510719-31-00

ClinicalTrials.gov

NCT06440967

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

To evaluate the efficacy of fezolinetant 45 mg once daily versus placebo on frequency and severity of moderate to severe VMS in women experiencing VMS due to adjuvant endocrine therapy for stage 0-3 hormone receptor-positive (HR+) breast cancer.

Secondary objectives 8

1. To evaluate the effect of fezolinetant 45 mg once daily versus placebo on patient-reported quality of life and sleep disturbance.
2. To evaluate the persistence of effect of fezolinetant 45 mg once daily versus placebo through 24 weeks.
3. To evaluate the safety of fezolinetant 45 mg once daily in women experiencing VMS due to adjuvant endocrine therapy for stage 0-3 HR+ breast cancer.
4. To evaluate the effect of fezolinetant 45 mg once daily versus placebo on the frequency and severity of moderate to severe VMS.
5. To evaluate the effect of fezolinetant 45 mg once daily versus placebo on responder rates where response is defined as meeting certain reductions in VMS frequency.
6. To evaluate the pharmacokinetics (PK) of fezolinetant.
7. To evaluate the effect of fezolinetant on PK of adjuvant endocrine therapies.
8. To evaluate the effect of fezolinetant 45 mg once daily versus placebo on patient-reported quality of life, sleep disturbance, and patients’ global assessments of VMS and sleep disturbance.

Conditions and MedDRA coding

Moderate to Severe Vasomotor Symptoms (VMS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant is born female, and at least 18 years of age at the time of signing the informed consent form (ICF).
2. 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.
3. 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.
4. 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).
5. Has an Eastern Cooperative Oncology Group (ECOG) score 0 or 1.
6. Has at least 12-month life expectation.
7. 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 9

1. Participant has diagnosis of metastatic breast cancer (stage 4).
2. 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.
3. Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent.
4. 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.
5. 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.
6. Participant has a history of endometrial hyperplasia (participant can be enrolled if she has undergone a hysterectomy) or uterine/endometrial cancer.
7. 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.
8. 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.
9. Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvant endocrine therapy being used, or any components of the formulations used.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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;
2. Change in the frequency of moderate to severe VMS from BL to week 12;
3. Change in the severity of moderate to severe VMS from BL to week 4;
4. Change in the severity of moderate to severe VMS from BL to week 12.

Secondary endpoints 12

1. 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.
2. 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.
3. Incidence and severity of treatment-emergent adverse events (TEAEs) including adverse events of special interest (AESIs), clinical laboratory assessments, vital signs and ECG.
4. 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.
5. Percent reduction of ≥ 50%, ≥ 75% and 100% in the frequency of moderate to severe VMS from BL to weeks 1, 4, 8 and 12.
6. 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.
7. 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.
8. 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;
9. 8b. Change in the PROMIS SD SF 8b Total (raw) Score from BL to weeks 4, 8, 12 and 24;
10. 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;
11. 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.
12. 8e PGI-S SD response (at least 2 levels of improvement from BL) at weeks 4, 8, 12 and 24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6111

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head Regulatory Affairs

Third parties 12

Locations

9 EU/EEA countries · 102 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 162 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications