PERgoveriS In Stratified Treatment for Assisted Reproductive Technique

NCT01297465 | Completed Phase 3 Results

• 2 other identifiers: EMR 200061-5042010-023534-23
• Study Type: interventional
• Target: 202
• Locations: 11 countries
• Sites: 23

Brief Summary

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).

Conditions

Assisted Reproductive Techniques; Reproductive Technology, Assisted

Keywords

Ovulation Induction; Ovarian Stimulation; Reproductive Technique, Assisted; Assisted Reproductive Technics; Assisted Reproductive Technique; Reproductive Technology, Assisted

Outcome Measures

Primary Outcomes (1)

• Total Number of Oocytes Retrieved

  The total number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body.

  OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}])

Secondary Outcomes (13)

• Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)

  Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])

• Total Number of Stimulation Treatment Days

  Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])

• Implantation Rate

  Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])

• Number of Fetal Sacs With Activity

  Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])

• Number of Fetal Hearts With Activity

  Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])

Study Arms (2)

Gonal-f® Plus Pergoveris®

ACTIVE COMPARATOR

Drug: Gonal-f®; Drug: Pergoveris®; Drug: Recombinant human chorionic gonadotropin (r-hCG)

Pergoveris®

EXPERIMENTAL

Drug: Pergoveris®; Drug: Recombinant human chorionic gonadotropin (r-hCG)

Interventions

Gonal-f® 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).

Also known as: Follitropin alfa

Gonal-f® Plus Pergoveris®

Pergoveris® 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.

Gonal-f® Plus Pergoveris®

Recombinant human chorionic gonadotropin (r-hCG) DRUG

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

Also known as: Ovidrel®, Ovitrelle®

Gonal-f® Plus Pergoveris®; Pergoveris®

Eligibility Criteria

• Age: 36 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A., Geneva: collaborator
• Merck A/S, Denmark: collaborator
• Merck OY, Finland: collaborator
• Merck Serono S.A.S, France: collaborator
• Merck Serono GmbH, Germany: collaborator
• Merck A.E., Greece: collaborator
• Merck B.V., Netherlands: collaborator
• Merck SP. Z.O.O., Poland: collaborator
• Merck Serono S.P.A., Italy: collaborator
• Merck Services U.K. Ltd, UK: collaborator
• LLC Merck, Russia: collaborator
• Merck spol. s r.o., Slovakia: collaborator
• Merck Pharma, K.S., Slovakia: collaborator

Study Sites (23)

Research Site

Dronninglund, Denmark

Location

Research Site

Fredericia, Denmark

Location

Research Site

Helsinki, Finland

Location

Research Site

Bondy, France

Location

Research Site

Bruges, France

Location

Research Site

Clamart, France

Location

Research Site

Thenon, France

Location

Research Site

Villeurbanne, France

Location

Research Site

Berlin, Germany

Location

Research Site

Halle, Germany

Location

Research Site

Heraklion, Crete, Greece

Location

Research Site

Pylaia, Thessaloniki, Greece

Location

Research Site

Athens, Greece

Location

Research Site

Bologna, Italy

Location

Research Site

Florence, Italy

Location

Research Site

Torino, Italy

Location

Research Site

Zwolle, Netherlands

Location

Research Site

Warsaw, Poland

Location

Research Site

Moscow, Russia

Location

Research Site

Samara, Russia

Location

Research Site

Bratislava, Slovakia

Location

Research Site

London, United Kingdom

Location

Research Site

Swansea, United Kingdom

Location

Related Publications (2)

• 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)

  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.

  PMID: 26194884 RESULT

MeSH Terms

Conditions

Helping Behavior

Interventions

follitropin alfa; pergoveris; Chorionic Gonadotropin; Ovidrel

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Salvatore Longobardi, MD

  Merck Serono S.P.A., Italy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2011
• First Posted: February 16, 2011
• Study Start: May 31, 2011
• Primary Completion: October 31, 2012
• Study Completion: October 31, 2012
• Last Updated: May 28, 2021
• Results First Posted: February 24, 2014

Record last verified: 2021-05

Locations

SL (1); GB (2); FR (5); GR (3); IT (3); FI (1); NL (1); PL (1); RU (2); DE (2); DK (2)