PERgoveriS In Stratified Treatment for Assisted Reproductive Technique

NCT ID: NCT01297465

Last Updated: 2021-05-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2012-10-31

Brief Summary

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This is a multicenter, multi-national, randomized, open-label comparative trial. After screening, the subjects will start down-regulation treatment on Day 21-22 of the cycle. Down-regulation treatment will start within 2 months following the screening visit. The routine long luteal phase protocol for gonadotropin-releasing hormone (GnRH) agonist treatment will be followed. Once down-regulation has been confirmed, a pregnancy test will be performed just before randomization and start of recombinant human follicle-stimulating hormone (r-hFSH) treatment to rule out any pre-existing pregnancy. If the result is negative, the subject will be randomly assigned to one of the two treatment arms of the trial:

* GONAL-f®: (Liquid Pen; 300 international unit \[IU\] of per day) stimulation Day 1-5 followed by Pergoveris® (vial/powder, 300 IU per day) from stimulation Day 6 and until required recombinant human chorionic hormone (r-hCG) criterion is met. The dose can be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.
* Pergoveris®: (vial/powder, 300 IU per day) from stimulation Day 1 and until required r-hCG criterion is met. The dose can be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.

Randomization across the two treatment arms will be kept balanced in a 1:1 ratio. Follicular development will be monitored according to the center's standard practice by ultrasound (US) and/or estradiol (E2) levels, until the protocol r-hCG requirement is met (i.e., at least one follicle greater than or equal to \[\>=\] 18 millimeter \[mm\] and two follicles \>=16 mm). After this, a single injection of r-hCG will be administered in order to induce final oocyte maturation.

At a time of 34-38 hours after r-hCG administration, oocytes will be recovered vaginally under US monitoring. Oocytes will then be fertilized in vitro and embryos replaced 2-5 days after oocyte recovery. Ovum pick up (OPU), in vitro fertilization (IVF), embryo transfer (ET) and luteal support will be performed as per center's standard practice.

A post-treatment safety visit will be performed for all subjects who received r-hCG (pregnant and non- pregnant) on Day 15-20 post-hCG. For subjects who have withdrawn from treatment (i.e. after starting Pergoveris® or Gonal-f® but before hCG is given) this visit will take place 20-30 days after their first Pergoveris® or Gonal-f® treatment injection (excluding pregnancy testing).

Detailed Description

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Conditions

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Assisted Reproductive Techniques Reproductive Technology, Assisted

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gonal-f® Plus Pergoveris®

Group Type ACTIVE_COMPARATOR

Gonal-f®

Intervention Type DRUG

Gonal-f® (follitropin alfa) 300 International Unit (IU) will be administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5).

Pergoveris®

Intervention Type DRUG

Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) administration day (at least 1 follicles \>= 18 mm). The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type DRUG

250 microgram of r-hCG will be administered once subcutaneously on r-hCG day (at least 1 follicles \>= 18 mm).

Pergoveris®

Group Type EXPERIMENTAL

Pergoveris®

Intervention Type DRUG

Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles \>= 18 mm). The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.

Recombinant human chorionic gonadotropin (r-hCG)

Intervention Type DRUG

250 microgram of r-hCG will be administered once subcutaneously on r-hCG day (at least 1 follicles \>= 18 mm).

Interventions

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Gonal-f®

Gonal-f® (follitropin alfa) 300 International Unit (IU) will be administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5).

Intervention Type DRUG

Pergoveris®

Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) administration day (at least 1 follicles \>= 18 mm). The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.

Intervention Type DRUG

Pergoveris®

Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles \>= 18 mm). The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.

Intervention Type DRUG

Recombinant human chorionic gonadotropin (r-hCG)

250 microgram of r-hCG will be administered once subcutaneously on r-hCG day (at least 1 follicles \>= 18 mm).

Intervention Type DRUG

Other Intervention Names

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Follitropin alfa Ovidrel® Ovitrelle®

Eligibility Criteria

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Inclusion Criteria

* Be a female subject justifying an in vitro fertilization and embryo transfer (IVF/ET) treatment
* Be between her 36th and 40th birthday (both included) at the time of the randomization visit
* Have early follicular phase (Day 2-4) serum level of basal follicle stimulating hormone (FSH less than or equal to (=\<)12 IU/L) measured in the center's local laboratory during the screening period (that is within 2 months prior to down-regulation start)
* A body mass index (BMI) less than (\<) 30 kilogram per square meter (kg/m\^2)
* Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
* Be willing and able to comply with the protocol for the duration of the trial
* Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care
* Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used

Exclusion Criteria

* Had \>= 2 previous ART cycles with a poor response to gonadotrophin stimulation defined as =\< 6 mature follicles and/or =\<4 oocytes collected in any previous IVF cycle or previous cycles with a hyper response defined as \>= 25 oocytes retrieved
* Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's medical responsible
* Had previous severe ovarian Hyperstimulation Syndrome (OHSS)
* Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
* Any contraindication to being pregnant and/or carrying a pregnancy to term
* History of 3 or more miscarriages (early or late miscarriages) due to any cause
* A clinically significant systemic disease
* Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner
* Known allergy or hypersensitivity to human gonadotrophin preparations
* Entered previously into this trial or simultaneous participation in another clinical trial.
* Pregnancy and lactation period
* Participation in another clinical trial within the past 30 days
Minimum Eligible Age

36 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck Serono S.A., Geneva

INDUSTRY

Sponsor Role collaborator

Merck A/S, Denmark

INDUSTRY

Sponsor Role collaborator

Merck OY, Finland

INDUSTRY

Sponsor Role collaborator

Merck Serono S.A.S, France

INDUSTRY

Sponsor Role collaborator

Merck Serono GmbH, Germany

INDUSTRY

Sponsor Role collaborator

Merck A.E., Greece

INDUSTRY

Sponsor Role collaborator

Merck B.V., Netherlands

INDUSTRY

Sponsor Role collaborator

Merck SP. Z.O.O., Poland

INDUSTRY

Sponsor Role collaborator

Merck Serono S.P.A., Italy

INDUSTRY

Sponsor Role collaborator

Merck Services U.K. Ltd, UK

INDUSTRY

Sponsor Role collaborator

LLC Merck, Russia

INDUSTRY

Sponsor Role collaborator

Merck spol. s r.o., Slovakia

INDUSTRY

Sponsor Role collaborator

Merck Pharma, K.S., Slovakia

INDUSTRY

Sponsor Role collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Salvatore Longobardi, MD

Role: STUDY_DIRECTOR

Merck Serono S.P.A., Italy

Locations

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Research Site

Dronninglund, , Denmark

Site Status

Research Site

Fredericia, , Denmark

Site Status

Research Site

Helsinki, , Finland

Site Status

Research Site

Bondy, , France

Site Status

Research Site

Bruges, , France

Site Status

Research Site

Clamart, , France

Site Status

Research Site

Thenon, , France

Site Status

Research Site

Villeurbanne, , France

Site Status

Research Site

Berlin, , Germany

Site Status

Research Site

Halle, , Germany

Site Status

Research Site

Heraklion, Crete, Greece

Site Status

Research Site

Pylaia, Thessaloniki, Greece

Site Status

Research Site

Athens, , Greece

Site Status

Research Site

Bologna, , Italy

Site Status

Research Site

Florence, , Italy

Site Status

Research Site

Torino, , Italy

Site Status

Research Site

Zwolle, , Netherlands

Site Status

Research Site

Warsaw, , Poland

Site Status

Research Site

Moscow, , Russia

Site Status

Research Site

Samara, , Russia

Site Status

Research Site

Bratislava, , Slovakia

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

Swansea, , United Kingdom

Site Status

Countries

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Denmark Finland France Germany Greece Italy Netherlands Poland Russia Slovakia United Kingdom

References

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H Behre, C Howles, S Longobardi. Luteinizing hormone supplementation from Day 1 versus 6 of ovarian stimulation in women aged 36-40 years: results from an open-label, randomized, multicentre, multinational trial. Human Reproduction. 2013;28(suppl 1)

Reference Type RESULT

Behre HM, Howles CM, Longobardi S; PERSIST Study Investigators. Randomized trial comparing luteinizing hormone supplementation timing strategies in older women undergoing ovarian stimulation. Reprod Biomed Online. 2015 Sep;31(3):339-46. doi: 10.1016/j.rbmo.2015.06.002. Epub 2015 Jun 15.

Reference Type RESULT
PMID: 26194884 (View on PubMed)

Other Identifiers

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2010-023534-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 200061-504

Identifier Type: -

Identifier Source: org_study_id

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