PERgoveriS In Stratified Treatment for Assisted Reproductive Technique (PERSIST)

This study has been completed.
Sponsor:
Collaborators:
Merck Serono S.A., Geneva
Merck A/S, Denmark
Merck OY, Finland
Merck Serono S.A.S, France
Merck Serono GmbH, Germany
Merck A.E., Greece
Merck B.V., Netherlands
Merck SP. Z.O.O., Poland
Merck Serono S.P.A., Italy
Merck Services U.K. Ltd, UK
LLC Merck, Russia
Merck spol. s r.o., Slovakia
Merck Pharma, K.S., Slovakia
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01297465
First received: February 15, 2011
Last updated: January 10, 2014
Last verified: January 2014

February 15, 2011
January 10, 2014
May 2011
October 2012   (final data collection date for primary outcome measure)
Total Number of Oocytes Retrieved [ Time Frame: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}]) ] [ Designated as safety issue: No ]
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.
Total number of oocytes retrieved per subject following ovarian stimulation. [ Time Frame: At 34-38 hours post r-hCG administration ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01297465 on ClinicalTrials.gov Archive Site
  • Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH) [ Time Frame: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
  • Total Number of Stimulation Treatment Days [ Time Frame: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
  • Implantation Rate [ Time Frame: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
    Implantation rate per reporting group was measured as the number of fetal sacs observed, divided by the number of embryos transferred multiplied by 100.
  • Number of Fetal Sacs With Activity [ Time Frame: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}]) ] [ Designated as safety issue: No ]
    Number of fetal sacs with activity was evaluated by ultrasound scan
  • Number of Fetal Hearts With Activity [ Time Frame: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}]) ] [ Designated as safety issue: No ]
    Number of fetal hearts with activity was evaluated by ultrasound scan
  • Clinical Pregnancy Rate [ Time Frame: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
    Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Clinical pregnancy rate was reported as total clinical pregnancy rate, clinical pregnancy rate per cycle started and per embryo transfer [ET]).
  • Number of Participants With Cancelled Cycles Due to Excessive or Insufficient Ovarian Response to Treatment [ Time Frame: S1 until Day 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
    An excessive ovarian response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An insufficient ovarian response: defined as 3 or less follicles of greater than or equal to 12 millimeter developing following at least 7 days of treatment.
  • Biochemical Pregnancies Rate [ Time Frame: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
    Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of human chorionic gonadotropin (hCG) in serum or urine and that does not develop into a clinical pregnancy. Participants with beta- hCG concentration greater than 10 international units per liter (IU/L) were considered as biochemical pregnant.
  • Number of Participants With Multiple Pregnancies [ Time Frame: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: No ]
    Multiple pregnancy was defined as the existence of more than one fetal sac with fetal heart activity.
  • Number of Participants With Early and Late Ovarian Hyper Stimulation Syndrome (OHSS) [ Time Frame: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: Yes ]
    Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. Early OHSS was defined as the onset of OHSS occurring within 9 days after oocyte retrieval and late OHSS was defined as the onset of OHSS occurring on or after day 10 from oocyte retrieval.
  • Number of Participants With Treatment-emergent Adverse Events [ Time Frame: Day 1 up to days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
  • Systolic and Diastolic Arterial Blood Pressure Assessments [ Time Frame: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: Yes ]
  • Heart Rate Assessments [ Time Frame: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days]) ] [ Designated as safety issue: Yes ]
  • Total dose of FSH used (in IU) [ Time Frame: After completion of stimulation (Day 1 to Day [Sn] ] [ Designated as safety issue: No ]
  • Total number of stimulation treatment days [ Time Frame: After completion of stimulation (Day 1 to Day [Sn]) ] [ Designated as safety issue: No ]
  • Implantation rate (fetal sacs per total number of embryos transferred) [ Time Frame: Days 35-42 post hCG ] [ Designated as safety issue: No ]
  • Number of foetal sacs and foetal hearts with activity as seen on an US scan on Day 35-42 post hCG (to confirm clinical pregnancy) [ Time Frame: Days 35-42 post hCG ] [ Designated as safety issue: No ]
  • Total and clinical pregnancy rate per subject (per cycle started, and per embryo transfer [ET]) [ Time Frame: Days 35-42 post hCG ] [ Designated as safety issue: No ]
  • Cycle cancellation prior to hCG [ Time Frame: During Stimulation Days ] [ Designated as safety issue: No ]
  • Number of biochemical pregnancies (by serum beta- hCG level) [ Time Frame: Days 35-42 post hCG ] [ Designated as safety issue: No ]
  • Multiple pregnancy [ Time Frame: Days 35-42 post hCG ] [ Designated as safety issue: No ]
  • Occurrence of any adverse events (early and late ovarian hyperstimulation syndrome (OHSS) [ Time Frame: Days 15-20 post hCG ] [ Designated as safety issue: Yes ]
  • Adverse events that are treatment-emergent, in accordance with the Pergoveris investigator brochure. [ Time Frame: Days 15-20 post hCG ] [ Designated as safety issue: Yes ]
  • Vital signs mainly systemic arterial blood pressure (systolic and diastolic), and heart rate. [ Time Frame: Days 15-20 post hCG ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
PERgoveriS In Stratified Treatment for Assisted Reproductive Technique
A Phase IIIB, Multicentre, Multinational, Randomized, Open-label Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® Day 1 to Day 5 Followed by Pergoveris® Starting Day 6 to Pergoveris® Starting Day 1 in Women Between 36 and 40 Years of Age Undergoing Assisted Reproductive Technique (ART)

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).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Assisted Reproductive Techniques
  • Reproductive Technology, Assisted
  • Drug: 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).
    Other Name: Follitropin alfa
  • 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.
  • 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.
  • 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).
    Other Names:
    • Ovidrel®
    • Ovitrelle®
  • Active Comparator: Gonal-f® Plus Pergoveris®
    Interventions:
    • Drug: Gonal-f®
    • Drug: Pergoveris®
    • Drug: Recombinant human chorionic gonadotropin (r-hCG)
  • Experimental: Pergoveris®
    Interventions:
    • Drug: Pergoveris®
    • Drug: Recombinant human chorionic gonadotropin (r-hCG)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
202
October 2012
October 2012   (final data collection date for primary outcome measure)

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
  • Other protocol specified inclusion criteria could also apply.

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
  • Other protocol specified inclusion criteria could also apply.
Female
36 Years to 40 Years
No
Contact information is only displayed when the study is recruiting subjects
Denmark,   Finland,   France,   Germany,   Greece,   Italy,   Netherlands,   Poland,   Russian Federation,   Slovakia,   United Kingdom
 
NCT01297465
EMR 200061-504, 2010-023534-23
Not Provided
Merck KGaA
Merck KGaA
  • Merck Serono S.A., Geneva
  • Merck A/S, Denmark
  • Merck OY, Finland
  • Merck Serono S.A.S, France
  • Merck Serono GmbH, Germany
  • Merck A.E., Greece
  • Merck B.V., Netherlands
  • Merck SP. Z.O.O., Poland
  • Merck Serono S.P.A., Italy
  • Merck Services U.K. Ltd, UK
  • LLC Merck, Russia
  • Merck spol. s r.o., Slovakia
  • Merck Pharma, K.S., Slovakia
Study Director: Salvatore Longobardi, MD Merck Serono S.P.A., Italy
Merck KGaA
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP