Clinical Trials Register

Summary
EudraCT Number:	2021-001685-38
Sponsor's Protocol Code Number:	2693-CL-0312
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-09-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Norway - NOMA

A.2

EudraCT number

2021-001685-38

A.3

Full title of the trial

A Phase 3b, Randomized, Double-blind, Placebo-controlled, 24-week Study to Assess the Efficacy and Safety of Fezolinetant in Menopausal Women Suffering from Moderate to Severe Vasomotor Symptoms (Hot Flashes) and Considered Unsuitable for Hormone Replacement Therapy.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to test how effective and safe fezolinetant is in women who have moderate to severe hot flashes due to menopause and who cannot take hormone therapy.

A.3.2

Name or abbreviated title of the trial where available

Daylight

A.4.1

Sponsor's protocol code number

2693-CL-0312

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Astellas Pharma Global Development, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Astellas Pharma Global Development, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma Europe B.V.
B.5.2	Functional name of contact point	Clinical Trial Unit RA
B.5.3	Address:
B.5.3.1	Street Address	Sylviusweg 62
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 BE
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715454006
B.5.5	Fax number	+31715455224
B.5.6	E-mail	ctu@astellas.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fezolinetant
D.3.2	Product code	ESN364
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FEZOLINETANT
D.3.9.1	CAS number	1629229-37-3
D.3.9.2	Current sponsor code	ESN364
D.3.9.4	EV Substance Code	SUB188609
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fezolinetant
D.3.2	Product code	ESN364
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FEZOLINETANT
D.3.9.1	CAS number	1629229-37-3
D.3.9.2	Current sponsor code	ESN364
D.3.9.4	EV Substance Code	SUB188609
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to Severe Vasomotor Symptoms (Hot Flashes) Associated with Menopause

E.1.1.1

Medical condition in easily understood language

Hot Flashes Associated with Menopause

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10020407
E.1.2	Term	Hot flashes
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of fezolinetant 45 mg versus placebo on the frequency of moderate to severe VMS

E.2.2

Secondary objectives of the trial

Key secondary: - To evaluate the efficacy of fezolinetant 45 mg versus placebo on the severity of moderate to severe VMS;
Secondary: - To evaluate the effect of fezolinetant 45 mg versus placebo on patient-reported sleep disturbance
- To evaluate the efficacy of fezolinetant 45 mg versus placebo on the frequency and severity of moderate to severe VMS
- To evaluate the safety and tolerability of fezolinetant 45 mg

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. IRB/IEC approved written informed consent and privacy language as per national regulations must be obtained from the participant prior to any study-related procedures.
2. Participant is born female, aged ≥ 40 years and ≤ 65 years of age at the screening visit
3. Participant must be seeking treatment or relief for VMS associated with menopause and confirmed as menopausal per one of the following criteria at the screening visit:
• Spontaneous amenorrhea for ≥ 12 consecutive months
• Spontaneous amenorrhea for ≥ 6 months with biochemical criterion of menopause (follicle-stimulating hormone [FSH] > 40 IU/L)
• Had bilateral oophorectomy ≥ 6 weeks prior to the screening visit (with or without hysterectomy)
• Had hysterectomy without oophorectomy and who meets the biochemical criterion of menopause (FSH > 40 IU/L)
4. Participant has VMS and is unsuitable to receive HRT (HRT contraindicated, HRT caution, HRT stoppers and HRT averse participants). The definitions for HRT unsuitable categories are provided below:
• HRT Contraindicated: participants with undiagnosed vaginal bleeding, history of breast cancer or estrogen dependent tumors; arterial thromboembolic disease (e.g., angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, venous thrombophilic disorder [e.g., deep vein thrombosis, pulmonary embolism]); hypersensitivity to estrogen and progesterone therapy or any of the excipients; or porphyria. Note: Participants with undiagnosed vaginal bleeding will be allowed in the study after appropriate assessment has been performed at the investigator’s discretion.
• HRT Caution: participants with history of diabetes mellitus, hyperlipidemia, smoking (current), migraine, obesity (body mass index > 29.9 kg/m2), systemic lupus erythematosus, epilepsy, family history of breast cancer in the first degree relative or mutation of breast cancer gene (BRCA1 and BRCA2)
• HRT Stoppers: participants who have discontinued HRT due to lack of efficacy, HRT-related side effects, advised by healthcare provider to stop due to length of time on HRT or due to participant’s age ≥ 60 years old
• HRT Averse: participants who made an informed choice to not take HRT after a consultation about the benefit risks of HRT
For HRT Contraindicated and HRT Caution participants, written documentation regarding the conditions listed must be present in the medical files of participants to qualify under these definitions. For HRT Stoppers for lack of efficacy and HRT-related side effects, accurate and exhaustive documentation must be provided, for example (and as applicable) length of HRT treatment and reason for determining inefficacy, type and duration of HRT-related side effects, etc. For HRT Averse participants, documentation must be provided regarding the nature and extent of the participant’s consultation with her healthcare provider, participant’s reason not to take HRT, etc.
5. Participant has a minimum average of 7 moderate to severe HFs (VMS) per day as recorded in the electronic diary during the last 10 days prior to randomization.
6. Participant is in good general health as determined on the basis of medical history, general physical examination, laboratory and other medical assessments in the opinion of the investigator.
7. Participant has a negative serology panel (including hepatitis B surface antigen, hepatitis C virus antibody and human immunodeficiency virus antibody screens).

E.4

Principal exclusion criteria

1. Participant uses a prohibited therapy for VMS (e.g., prescription, over-the-counter or herbal) prior to screening and for the duration of treatment with IP. Refer to [Section 6.8 Concomitant Therapy and Section 10.4 Appendix 4: List of Excluded Concomitant Medications] for a list of prohibited therapies.
2. Participant has known documented substance abuse or alcohol addiction within 6 months of screening.
3. Participant has history of a malignant tumor within the last 5 years, except for basal cell carcinoma.
4. Participant has endometrial thickness > 8 mm on the locally read screening transvaginal ultrasound (TVU) or any clinically significant findings that that would make the participant ineligible in the opinion of the investigator.
5. Participant has history of severe allergy, hypersensitivity or intolerance to the IP and/or any of its excipients.
6. Participant has a history of seizures or other convulsive disorders unless well controlled.
7. Participant has a medical condition or chronic disease (including history of neurological [including cognitive], renal, cardiovascular, gastrointestinal, pulmonary [e.g., moderate asthma], endocrine or gynecological disease) or malignancy that could confound interpretation of the study outcome in the opinion of the investigator.
8. Participant has any of the following:
• active liver disease,
• jaundice,
• elevated liver aminotransferases at screening (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]),
• elevated total bilirubin (TBL) or direct bilirubin (DBL) > 1.5 x upper limit of normal (ULN),
• elevated International Normalized Ratio (INR) >1.5 (unless participant is receiving anticoagulant therapy) or
• elevated alkaline phosphatase (ALP).

Participants with mildly elevated ALT or AST up to 1.5 × ULN can be enrolled if TBL and DBL are normal.

Participants 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.

Participants with Gilbert’s syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.

9. Participant has creatinine > 1.5 × ULN or estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula ≤ 59 mL/min per 1.73 m2 at the screening visit.
10. Participant has a history of suicide attempt or suicidal behavior within the last 12 months.
11. Participant has participated in another interventional study within the last 30 days prior to screening and for the duration of the study.
12. Participant who has been previously enrolled in a clinical study with fezolinetant.
13. Participant is unable or unwilling to complete the study procedures.
14. Participant has any condition, which in the investigator’s opinion, makes the participant unsuitable for study participation.

E.5 End points

E.5.1

Primary end point(s)

- Mean change in the frequency of moderate to severe Vasomotor Symptoms (VMS) from baseline to week 24

E.5.1.1

Timepoint(s) of evaluation of this end point

●Baseline to week 24.

E.5.2

Secondary end point(s)

- Mean change in the severity of moderate to severe VMS from baseline to week 24;
- Mean change in the patient-reported sleep disturbance by the Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b (PROMIS SD SF 8b) total score from baseline to week 24;
- Mean change in the frequency of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20;
- Mean change in the severity of moderate to severe VMS from baseline to weeks 1, 4, 8, 12, 16 and 20;
- Mean percent change in the frequency of moderate and severe VMS from baseline to weeks 1, 4, 8, 12, 16, 20 and 24;
- Responder of percent reduction ≥ 50%, ≥ 75% and at 100% in the frequency of moderate and severe VMS from baseline to weeks 1, 4, 8, 12, 16, 20 and 24;
- Frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory assessments, vital signs and electrocardiogram (ECG);

E.5.2.1

Timepoint(s) of evaluation of this end point

●Up to week 27

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability;

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Russian Federation

Turkey

Belgium

Czechia

Denmark

Finland

France

Germany

Hungary

Italy

Netherlands

Norway

Poland

Spain

Sweden

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last subject last visit/procedure

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

440

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

252

F.4.2.2

In the whole clinical trial

440

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-04-20

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