- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00249834
Safety and Efficacy of Pre-defined, Fixed Dose of Gonal-f Pen Based on Subject Baseline Characteristics in Subjects Undergoing in Vitro Fertilization (IVF) (CONSORT)
August 29, 2017 updated by: Merck KGaA, Darmstadt, Germany
A Phase IIIB/IV, Open Label Study to Assess the Efficacy and Safety of a Pre-defined, Fixed Dose of Gonal-f® (Filled-by-Mass in a Prefilled Pen) Based on Subject Baseline Characteristics, for Ovarian Stimulation in Subjects Undergoing in Vitro Fertilization (IVF)
Clinical validation of the assisted reproductive technology (ART) treatment guidelines, which determine the optimal dose of recombinant human follicle stimulating hormone (r-hFSH) based on subject baseline characteristics/predictors of ovarian response.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
166
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Paris, France
- Medical Information
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 34 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria
- Be an infertile subject justifying an in-vitro fertilization/embryo transfer (IVF/ET) treatment.
- Have a male partner with semen analysis within the past six months prior to study entry 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.
- Be between her 18th and 35th birthday (35 not included).
- Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length.
- Have early follicular phase (Day 2-4) serum levels within the last 3 months prior to study entry of:
- Follicle stimulating hormone (FSH) greater than or equal to (>=) 12 International units per liter (IU/L), and
- Oestradiol (E2) within center's local normal laboratory range values.
- Presence of both ovaries.
- Have a uterine cavity without abnormalities, which, in the investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed within the last 3 years using ultrasound (US), hysteroscopy (HSC), or hysterosalpingography (HSG).
- Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to study entry.
- Have at least one wash-out cycle (defined as >= 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotrophin releasing hormone (GnRH) agonist therapy.
- Have a negative pregnancy test prior to beginning GnRH agonist therapy.
- Be willing and able to comply with the protocol for the duration of the study. Have given written informed consent, prior to any study-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.
Exclusion Criteria:
- Had 2 previous ART cycles with a poor response to gonadotrophin stimulation, defined as less than or equal to (<=) 5 mature follicles and/or <=3 oocytes collected in any previous IVF cycle or hyper response, defined as >=25 oocytes retrieved.
- Any medical condition, which in the judgement 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 Serono's Therapeutic Director.
- Had previous severe ovarian hyperstimulation syndrome (OHSS).
- A body mass index (BMI) greater than (>) 30 kilogram per square meter (kg/m^2)
- Any contraindication to being pregnant and/or carrying a pregnancy to term.
- Extra-uterine pregnancy within the last 3 months.
- History of 3 or more miscarriages (early or late miscarriages) due to any cause.
- Tumours of the hypothalamus and pituitary gland.
- Ovarian enlargement or cyst of unknown aetiology.
- Ovarian, uterine or mammary cancer.
- A clinically significant systemic disease.
- Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus.
- Abnormal gynaecological bleeding of undetermined origin.
- Known allergy or hypersensitivity to human gonadotrophin preparations.
- Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years.
- Entered previously into this study or simultaneous participation in another clinical trial
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Gonal-f 112.5 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 37.5 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 75 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 150 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 187.5 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 225 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 262.5 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
Experimental: Gonal-f 300 IU
|
GONAL-f (follitropin alfa) will be administered subcutaneously based on ART treatment guidelines, which determined the optimal dose of r-hFSH based on subject baseline characteristics/predictors of ovarian response throughout stimulation cycle.
Other Names:
When at least 1 follicle greater than or equal to (>=) 18 millimeter (mm) and 2 follicles >=16 mm in diameter develop, 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) will be administered.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Oocytes Retrieved
Time Frame: Ovum pick up day (34 to 38 hours post r-hCG administration)
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Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated.
Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
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Ovum pick up day (34 to 38 hours post r-hCG administration)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Dose of Recombinant Human Follicle Stimulating Hormone (r-hFSH)
Time Frame: up to end of stimulation cycle (approximately 31 days)
|
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
|
up to end of stimulation cycle (approximately 31 days)
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Mean Number of Ovarian Stimulation Days
Time Frame: up to end of stimulation cycle (approximately 31 days)
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The mean number of stimulation days were determined based on the treatment administration information collected in the case report form.
Ovarian stimulation included time from first r-hFSH injection (stimulation Day) until day on which r-hCG was administered (r-hCG day).
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
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up to end of stimulation cycle (approximately 31 days)
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Percentage of Cycles Cancelled Due to Excessive or Inadequate Response to r-hFSH
Time Frame: up to end of stimulation cycle (approximately 31 days)
|
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
|
up to end of stimulation cycle (approximately 31 days)
|
Number of Subjects Needing Dose Adjustment
Time Frame: 6 days post r-hFSH treatment
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Number of subjects needing increase in dose, decrease in dose or increase and decrease both in dose were reported.
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
|
6 days post r-hFSH treatment
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Mean Daily Recombinant Human Follicle Stimulating Hormone (r-hFSH) Dose
Time Frame: up to end of stimulation cycle (approximately 31 days)
|
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
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up to end of stimulation cycle (approximately 31 days)
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Embryo Implantation Rate
Time Frame: 35-42 days post r-hCG administration
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Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
|
35-42 days post r-hCG administration
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Overall Pregnancy Rate, Clinical Rate and Multiple Pregnancy Rate
Time Frame: 35-42 days post r-hCG administration
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Overall pregnancy rate was defined as the percentage of subjects with serum beta-hCG levels greater than 10 IU/L.
Clinical pregnancy rate was defined as the percentage of subjects with at least 1 ultrasound confirmed gestational sac, with or without foetal heart activity.
Multiple pregnancy rate was defined as the percentage of subjects with more than 1 ultrasound confirmed gestational sac in the uterus with fetal heart activity.
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects.
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35-42 days post r-hCG administration
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Olivennes F, Howles CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V; CONSORT study group. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2009 Feb;18(2):195-204. doi: 10.1016/s1472-6483(10)60256-8.
- Olivennes F, Howies CM, Borini A, Germond M, Trew G, Wikland M, Zegers-Hochschild F, Saunders H, Alam V. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2011 Feb;22 Suppl 1:S73-82. doi: 10.1016/S1472-6483(11)60012-6.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 22, 2004
Primary Completion (Actual)
January 16, 2006
Study Completion (Actual)
January 16, 2006
Study Registration Dates
First Submitted
November 4, 2005
First Submitted That Met QC Criteria
November 4, 2005
First Posted (Estimate)
November 7, 2005
Study Record Updates
Last Update Posted (Actual)
March 30, 2018
Last Update Submitted That Met QC Criteria
August 29, 2017
Last Verified
August 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 25198
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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