Clinical Trials Register

Summary
EudraCT Number:	2020-004329-21
Sponsor's Protocol Code Number:	PE-PMA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-05-24
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004329-21

A.3

Full title of the trial

Reduction of progesterone elevation at trigger in poor responder Bologna’ criteria patients after controlled ovarian stimulation with long acting standard stimulation protocol compared with conventional daily protocol: a single center prospective randomized Fase IV trial

Riduzione dell’incidenza di rialzo precoce del progesterone il giorno dell’induzione dell’ovulazione dopo stimolazione ovarica con il protocollo a lunga durata d’azione rispetto al protocollo giornaliero convenzionale nelle pazienti con prevista scarsa risposta ovarica secondo i criteri di Bologna: studio monocentrico, randomizzato, di fase IV

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PE-PMA

A.4.1

Sponsor's protocol code number

PE-PMA

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	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MERCK SHARP & DOHME CORP.
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	Ospedale San Raffaele
B.5.2	Functional name of contact point	Ospedale San Raffaele
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390226436228
B.5.5	Fax number	+390226434311
B.5.6	E-mail	papaleo.enrico@hsr.it

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	ELONVA - 150 MCG - SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - SIRINGA PRERIEMPITA(VETRO) - 0.5 ML 1 SIRINGA PRERIEMPITA + 1 AGO
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Elonva
D.3.2	Product code	[Elonva]
D.3.4	Pharmaceutical form	Solution for injection
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	corifollitropina alfa
D.3.9.2	Current sponsor code	Elonva - Corifollitropina alfa
D.3.9.3	Other descriptive name	CFA
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	PUREGON - 300 UI/0.362 ML SOLUZIONE INIETTABILE 1 CARTUCCIA USO SOTTOCUTANEO
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Puregon
D.3.2	Product code	[Puregon]
D.3.4	Pharmaceutical form	Solution for injection
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	FOLLITROPINA BETA
D.3.9.2	Current sponsor code	Puregon - Ormone follicolo-stimolante ricombinante
D.3.9.3	Other descriptive name	rFSH
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	833
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Patient with poor ovarian response

Pazienti con ridotta risposta alla stimolazione ovarica controllata

E.1.1.1

Medical condition in easily understood language

Patient with poor ovarian response

Pazienti con ridotta risposta alla stimolazione ovarica controllata

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	LLT
E.1.2	Classification code	10021935
E.1.2	Term	Infertility, female, associated with anovulation
E.1.2	System Organ Class	100000004872

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The overarching objective of this research is to generate clinical evidence to argue the bene-fits of long acting stimulation protocol compared to the daily stimulation protocol in poor ovarian responders.

L’obiettivo principale dello studio è di provare se ci siano evidenze cliniche sui benefici della stimolazione ovarica a lunga durata d’azione rispetto al protocollo di stimolazione giornaliera nelle pazienti con prevista ridotta risposta ovarica.

E.2.2

Secondary objectives of the trial

To reduce the freeze-all IVF cycles due to prema-ture PE
To increase the n° of oocytes collected at ovum re-trieval
To increase the fertilization rate
To increase the n° of embryo available
To increase the pregnancy rate
To increase the ongoing pregnancy rate (vital fetus at 20 weeks of gestation)

Ridurre il numero di cicli IVF freeze-all dovuti a rialzo precoce del progesterone
Aumento del numero di ovociti recuperati al prelievo ovocitario
Aumento il tasso di fertilizzazione
Aumento del numero di embrioni
Aumento del tasso di gravidanza
Aumento del tasso di gravidanze evolutive (feto vitale a 20 settimane di gestazione)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women undergoing IVF cycle, aged between 25 and 42 years, normal BMI (18.5-24.9 kg/m2), AMH level < 1.1 ng/ml and/or AFC < 5 follicles and/or < 3 oo-cytes retrieved in previous cycle, regular menstrual cycles, FSH on cycle day 3 < 20 IU/L, who have signed informed consent

Donne con indicazione a ciclo di fecondazione artificiale di età compresa tra i 25 e i 42 anni, BMI normale (18.5-24.9 kg/m2), AMH < 1.1 ng/ml e/o AFC < 5 follicoli e/o < 3 ovociti recuperati in un ciclo precedente, cicli mestruali regolari, FSH< 20 UI/L il terzo giorno di ciclo, che hanno firmato il consenso informato previsto per lo studio

E.4

Principal exclusion criteria

BMI >25 or <18, PCOS, history of untreated autoimmune, endocrine or metabolic disorders, ovarian cystectomy or oophorectomy, FSH >= 20 lU/L, Kidney diseases, Malignant gynecological cancer, Hypersensitivity to investigated drugs , contraindication for pregnancy

BMI >25 o <18, PCOS, storia di patologia autoimmune non trattata, disordini endocrino-metabolici, interventi ovarici pregressi, FSH >= 20 UI/L, insufficienza renale, tumori maligni ginecologici, ipersensibilità ai farmaci utilizzati, controindicazioni all’ottenimento di una gravidanza

E.5 End points

E.5.1

Primary end point(s)

Reduction in the proportion of subjects with progesterone > 1.1 ng/ml on the day of triggering (day + 13) in the experimental group (Expected 5%) compared to the control group (Expected 25%)

Riduzione percentuale delle pazienti con progesterone > 1.1 ng/ml al giorno dell’induzione (giorno + 13) nel gruppo di studio (Atteso 5%) rispetto al gruppo di controllo (Atteso 25%)

E.5.1.1

Timepoint(s) of evaluation of this end point

on the day of triggering (day + 13)

al giorno dell’induzione (giorno + 13)

E.5.2

Secondary end point(s)

Comparison of the n° of oocytes collected between the two Arms at day + 14; Percentage of fertilized oocytes at day +15 of ex-perimental group compared to the control group; Total n° of embryos obtained at day +17 of experi-mental group compared to the control group; Percentage of positive pregnancy test at day +31 of experimental group compared to the control group; Percentage of abortion at week 20th of experimental group compared to the control group; Total n° of embryos cryopreserved at day +21 of ex-perimental group compared to the control group

Numero di ovociti recuperati al prelievo ovocitario nei due gruppi (giorno + 14); Percentuale di ovociti fecondati al giorno +15 del gruppo sperimentale rispetto al gruppo di controllo; Numero di embrioni ottenuti il giorno + 17 nel gruppo di studio rispetto al gruppo di controllo; Percentuale di test di gravidanza positivo al giorno +31 del gruppo sperimentale rispetto al gruppo di controllo; Percentuale di aborti alla settimana 20 del gruppo sperimentale rispetto al gruppo di controllo; Numero di embrioni congelati il giorno +21 nel gruppo di studio rispetto al gruppo di controllo

E.5.2.1

Timepoint(s) of evaluation of this end point

day + 14; day +15; day +17; day +31; week 20th; day +21

giorno + 14; giorno +15; giorno 17; giorno +31; settimana 20; giorno +21

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

E.6.5

Efficacy

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

LVLS

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:

110

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

Yes

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

110

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

110

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)

Normal clinical practice

Normale pratica clinica

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

2021-01-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-05-06

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