Clinical Trials Register

Summary
EudraCT Number:	2021-001785-38
Sponsor's Protocol Code Number:	000401
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-06-16
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

France - ANSM

A.2

EudraCT number

2021-001785-38

A.3

Full title of the trial

A randomised, controlled, assessor-blind, parallel groups, multicentre, multinational trial comparing the ovarian response of a starting dose of 15 µg follitropin delta (REKOVELLE) to a starting dose of 225 IU follitropin alfa (GONAL-F) in conventional regimens in controlled ovarian stimulation in women undergoing an assisted reproductive technology programme

A.3.1

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

A trial to compare the ovarian response of REKOVELLE and GONAL-F in conventional dosing in women undergoing controlled ovarian stimulation

A.3.2

Name or abbreviated title of the trial where available

ADAPT-1

A.4.1

Sponsor's protocol code number

000401

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1267-1119

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	Ferring Pharmaceuticals A/S
B.1.3.4	Country	Denmark
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	Ferring Pharmaceuticals A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ferring Pharmaceuticals A/S
B.5.2	Functional name of contact point	Global Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Amager Strandvej 405
B.5.3.2	Town/ city	Kastrup
B.5.3.3	Post code	2770
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+458833 8834
B.5.6	E-mail	DK0-Disclosure@ferring.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	Yes
D.2.1.1.1	Trade name	REKOVELLE
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Pharmaceuticals A/S
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FOLLITROPIN DELTA
D.3.9.1	CAS number	146479-72-3
D.3.9.2	Current sponsor code	FE 999049
D.3.9.3	Other descriptive name	human recombinant follicle-stimulating hormone
D.3.9.4	EV Substance Code	SUB178607
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	33.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Comparator
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	Yes
D.2.1.1.1	Trade name	GONAL-F
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	follitropin alfa
D.3.9.1	CAS number	56832-30-5
D.3.9.3	Other descriptive name	FOLLITROPIN ALFA
D.3.9.4	EV Substance Code	SUB12426MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Infertility in women undergoing assisted reproductive technologies (ART) such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle

E.1.1.1

Medical condition in easily understood language

Infertility - Inability to conceive children

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10021928
E.1.2	Term	Infertility female
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

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 compare a starting dose of 15 µg REKOVELLE to a starting dose of 225 IU GONAL F in conventional regimens with respect to ovarian response in women undergoing controlled ovarian stimulation

E.2.2

Secondary objectives of the trial

• To compare the follicular development, endocrine profile and embryo development associated with conventional dosing of REKOVELLE and GONAL-F
• To compare the treatment efficiency associated with conventional dosing of REKOVELLE and GONAL-F
• To compare the safety profile associated with conventional dosing of REKOVELLE and GONAL-F

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed Consent Form signed prior to screening evaluations.
2. In good physical and mental health.
3. Pre-menopausal females between the ages of 18 and 40 years. The subjects must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomisation.
4. Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
5. Infertility for at least one year before randomisation for subjects ≤37 years or for at least 6 months for subjects ≥38 years (not applicable in case of tubal or severe male factor infertility).
6. Regular menstrual cycles of 21-35 days (both inclusive), presumed to be ovulatory.
7. Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, without evidence of significant abnormality (e.g. no endometrioma greater than 3 cm, and no enlarged ovaries or ovarian cyst not due to polycystic ovarian syndrome, which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) within 1 year prior to randomisation. Both ovaries must be accessible for oocyte retrieval.
8. Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomisation).

E.4

Principal exclusion criteria

1. Primary ovarian failure.
2. Known endometriosis stage III-IV.
3. Considered unsuitable for controlled ovarian stimulation with a dosing regimen corresponding to approximately 225 IU/day gonadotropin, as judged by the investigator.
4. History of previous episode of OHSS or exuberant ovarian response to gonadotropins, and polycystic ovarian syndrome.
5. One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound prior to randomisation on stimulation day 1 (puncture of cysts is allowed prior to randomisation).
6. Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the trial with the exception of controlled thyroid function disease.
7. Known tumours of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.
8. Fibroid tumours of the uterus incompatible with pregnancy.
9. Currently breast-feeding.
10. Undiagnosed vaginal bleeding.
11. Findings at the gynaecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
12. Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomisation) or contraindication to pregnancy.
13. Use of fertility modifiers during the last menstrual cycle before randomisation, including dehydroepiandrosterone (DHEA) or cycle programming with oral contraceptives, progestogen or estrogen preparations.
14. Hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial.
15. Previous participation in the trial.
16. Use of any non-registered investigational drugs during the last 3 months prior to randomisation

E.5 End points

E.5.1

Primary end point(s)

Number of oocytes retrieved

E.5.1.1

Timepoint(s) of evaluation of this end point

Oocyte retrieval will take place 36h (±2h) after triggering of final follicular maturation

E.5.2

Secondary end point(s)

• Number of follicles (total and by size category) at end-of-stimulation
• Serum concentrations of estradiol and progesterone at end-of-stimulation
• Number of fertilised oocytes and fertilisation rate
• Number of blastocysts (total and by quality)
• Total gonadotropin dose and number of stimulation days
• Early OHSS (overall and by grade) and/or preventive interventions for early OHSS

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoint is included in the relevant endpoint

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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

Yes

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

France

Spain

Germany

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

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

End of trial is Post-trial follow-up period completed Q1 2024

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:

300

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

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

240

F.4.2.2

In the whole clinical trial

300

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

2022-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-12-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-06-21

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