Clinical Trials Register

Summary
EudraCT Number:	2017-000189-31
Sponsor's Protocol Code Number:	PRI04/2016
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-03-14
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-000189-31

A.3

Full title of the trial

Optimization and Safety Testing of Hormone Normalization Therapy
in Advanced Maternal Age Infertile Women

A Hormon Normalizációs Kezelés optimalizálása és
biztonságosságának vizsgálata előrehaladodott anyai korú meddő
nőbetegeken

A.3.1

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

Optmization and Safety Testng of a Therapy to Prevent Female
Infertlity Caused by Advanced Reproductive Age

A Hormon Normalizációs Kezelés optimalizálása és
biztonságosságának vizsgálata előrehaladodott anyai korú meddő
nőbetegeken

A.3.2

Name or abbreviated title of the trial where available

Hormone Normalization Therapy

Hormon Normalizációs Kezelés

A.4.1

Sponsor's protocol code number

PRI04/2016

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	Pannon Reprodukciós Intézet B.1.2
B.1.3.4	Country	Hungary
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	Pannon Reprodukciós Intézet
B.4.2	Country	Hungary
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pannon Reprodukciós Intézet
B.5.2	Functional name of contact point	Attila Török, MD
B.5.3	Address:
B.5.3.1	Street Address	Bartok Bela Str. 1.-3
B.5.3.2	Town/ city	Tapolca
B.5.3.3	Post code	8300
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3687510-365
B.5.5	Fax number	+3687510-366
B.5.6	E-mail	drtoroka@t-online.hu

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	Decapeptyl
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Magyarország Kft
D.2.1.2	Country which granted the Marketing Authorisation	Hungary
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	Decapeptyl
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

The therapy is intended to treat infertility that is caused by declining egg quality that occurs with advanced maternal age. The purpose of this pilot trial is to optimize the therapeutic protocol. This will result in standardization of the therapeutic regimen. Once this standardization has been achieved, a statistically powered trial will be performed to test the efficacy of the therapy for increasing the rates of pregnancy and healthy live borns.

A terápia célja az, hogy kezelje az idősödő nők romló petesetminőségéből adódó meddőséget. Ennek a vizsgálatnak csupán az a célja, hogy optimalizálja az ehhez szükséges terápiás protokollt. Ennek eredményeképpen kapunk egy standardizált terápiás sémát. Ha ez megvan, egy újabb, nagyobb esetszámon végzett vizsgálat fogja tesztelni a kezelés hatékonyságát meddőségben - a terhességi ráták és élveszületések növekedésével.

E.1.1.1

Medical condition in easily understood language

The therapy is to prevent infertility due to aging of the mother. This trial will optimize the therapy and provide safety assessments.

A kezelés célja, hogy az anya kora elenére megőrizze a termékenységet. Ez a vizsgálat optimalizálja a kezeléstés ellenőrzi annak biztonságosságát.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

(1) normalize FSH to young levels for each phase of the three cycles of HNT in both the follicular (FP) and luteal (LP) phases;
(2) achieve normal follicle growth and ovulation;
(3) observe normal menstrual function each cycle;
(4) Preliminary assessments of safety by regular monitoring comprised of physician examinations, ultrasounds and blood tests, and frequent communications with the fertility treatment staff.

1. Fiatal korú nők értékeire beállítani az FSH szintet a három ciklus
mindkét fázisában, a follikuláris (FP) és a lutealis (LP) fázisban is;
2. Normális tüszőnövekedés és ovuláció elérése
3. Normális menstruációs működés megfigyelése
4. A biztonságosság megítélése rendszeres monitorozással, fizikális vizsgálattal, ultrahang és vértesztekkel, valamint a rendszeres kommunikáció ezügyben a kezelést végző csapattal

E.2.2

Secondary objectives of the trial

(1) Achievement of pregnancy at end of treatment regimen
(2) lengthen the FP to approximate the duration of the FP that is typically experienced by a young and fertile woman.
(3) Normalization of E2 levels across FP and LP of Cycles 1, 2, and 3.

1. A kezelési folyamat végén terhesség létrejötte
2. A follikuláris fázis megnyújtása annyira, hogy a fiatal, fertilis nőkre
jellemző értéket kapjunk
3. Az E2 szintek normalizálása a FP és a LP alatt az 1, 2 és 3.
ciklusokban.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

● Age 35-44
● (1) One year or more of infertility that occurred under the age of 35,
or 6 months or more of infertility since the age of 35; or (2) one or more
previous miscarriages that occurred at age 35 or over. Miscarriages
must be either idiopathic, or attributable to autosomal aneuploidy; or (3)
one or more trisomic pregnancies that occurred over age 35
● FSH ≥13 and ≤40 IU/L on Day 3 of Cycle 0.
● Regular menstrual cycles of 15-32 days duration.
● Levels of Anti-Müllerian Hormone (AMH) between 0.1 and 1.0 ng/ml
● Patency of both fallopian tubes

• 35-44 éves életkor
• 1 évnél hoszabb meddőség 35 éves kor alatti időszakában, 6
hónapnál hoszabb meddőség 35 éves kor fölött
• FSH ≥13 és ≤40 IU/L a 0. Ciklus 3. Napján
• Rendszeres menstruációs ciklus (15-32nap)
• AMH 0,1 és 1 ng/ml között
• Ép méhkürtök

E.4

Principal exclusion criteria

• BMI less than 18 or more than 32
• Confounding untreated infertility conditions: maternal karyotypic
abnormalities if there is a history of RPL; PCOS; or untreated
antiphospholipid, lupus anticoagulant, hypothyroidism, hyperthyroidism,
or hyperprolactinemia
• Uncorrected abnormal uterine anatomy that would preclude pregnancy or would be likely to result in pregnancy losses
• Endometritis
• Medical contraindications to pregnancy
• Anti-cholesterol medications
• Previous chemotherapy or pelvic radiation for cancer
• Known hypersensitivity to GnRHa, FSH, hCG, E2, or progesterone medications

• BMI kisebb, mint 18 vagy nagyobb, mint 32
• Kezeletlen, meddőséget okozó állapotok (PCOS, anti-foszfolipid sy.,
hypo- vagy hyperthireoidizmus, stb.)
• Terhességet kizáró méh anatómiai rendellenesség
• Endometritis
• Terhesség orvosilag ellenjavallt
d• Cholesterin csökkentö gyógyszerek
• Korábbi rák ellenes chemotherapiás kezelés vagy besugárzás
• Ismert gyógyszerérzékenység az alkalmazott készítményekref

E.5 End points

E.5.1

Primary end point(s)

(1) Serum FSH levels throughout Cycles 0, 1, 2, and 3
(2) kinetics of follicle growth in vaginal ultrasounds (u/s) and via E2 levels during late FP; confirmed ovulation via serum preogsterone and u/s
(3) measurement of endometrial thickness in U/s; measurement of FP and LP length; reports of patient on menstrual flow vs. that of untreated cycles
(4) Preliminary assessments of safety by regular monitoring comprised of physician examinations, ultrasounds and blood tests, and frequent communications with the fertility treatment staff.

1. Szérum FSH szintek a 0, 1, 2, 3 ciklusokban
2. A tüszőnövekedés kinetikája hüvelyi ultrahang és E2 vizsgálatokkal a follikuláris fázis végén, ovuláció igazolása szérum progeszteron és
ultrahang vizsgálatokkal
3. Az endometrium vastagságának mérése ultrahanggal, az FP és LP hosszának mérése, a beteg beszámolója a menstruációjáról, mindez összehasonlítva a nem kezelt ciklusokkal
4. A biztonságosság megítélése fizikai vizsgálatok, ultrahangvizsgálatok, laboratóriumi vizsgálatok és a beteg beszámolója alapján

E.5.1.1

Timepoint(s) of evaluation of this end point

(1) Serum FSH levels early, mid, and late FP and LP in Cycles 0, 1, 2, and 3
(2) Every other day or every day u/s to record follicular diameters, and serum E2 levels ; serum preogsterone and u/s for confirmation of corpora lutea 3 days post hCG shot
(3) endometrial thickness u/s in FP; measurement of FP and LP length by comparing day of LH surge/hCG shot to LMP in Cycles 0, 1, 2, and 3;
reports of patient on menstrual flow vs. that of untreated cycles
(4) Safety monitoring will occur throughout all 4 cycles of trial participation.

1. Szérum FSH szintek a korai, közép és késői follikuláris fázisban illetve a lutealis fázisban a 0, 1, 2, 3 ciklusokban
2. Minden másnap, vagy akár minden nap a tüsző átmérőjének rögzítése UH segítségével és E2, progesteron mérésekkel, a hCG injekció után
három nappal a sárgatest UH ellenőrzése
3. Endometrium vastagság, UH vizsgálata a follikuláris fázisban, az FP és
LP hosszának mérése az LH csúcs időpontját alapul véva a 0, 1, 2, 3 ciklusokban - összehasonlítva a kezeletlen ciklusokkal
4. A biztonságosság monitorozása a 4 ciklusban

E.5.2

Secondary end point(s)

(1) hCG pregnancy test at end of treatment regimen
(2) FP length in Cycles 0, 1, 2, and 3
(3) Normalization of E2 levels across FP and LP of Cycles 1, 2, and 3

1. hCG terhességi teszt a kezelés végén
2. az FP hossza a 0, 1, 2, 3 ciklusokban
3. Az E2 szintek normalizálása a follikuláris és a lutealis fázisokban az 1,
2, 3 ciklusokban

E.5.2.1

Timepoint(s) of evaluation of this end point

(1) hCG pregnancy test at end of LP in Cycle 3
(2) Compare differences in duration between day of LH surge/hCG shot and LMP in each of Cycles 0, 1, 2, and 3.
(3) Measurement of serum E2 levels in early, mid and late LP in Cycles 1, 2, and 3 vs. Cycle 0

1. hCG terhességi teszt a lutealis fázis végén a 3. ciklusban
2. Összehasonlítani az eltéréseket az LH csúcs/hCG injekció napján mindhárom ciklusban
3. E2 szintek mérése a korai, közép és késői follikuláris fázisban az 1, 2, 3 ciklusokban - a 0. ciklussal összehasonlítva

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Pilot, beavatkozással járó, prospektív, nem kontrollált

Pilot, interventional, prospective, non-controlled study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

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.8.5

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

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

Az utolsó beteg utolsó vizitje

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:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2017-03-14.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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.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)

Regular pregnancy followup

Szokásos terhesgondozás

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

2017-05-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-08

P. End of Trial
P.	End of Trial Status	Ongoing

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