Back to resultsMulti-centre Study to Compare Efficacy and Safety of AFOLIA and Gonal-f in Women for Assisted Reproductive Treatment
Primary Purpose
Infertility
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Follitropin alfa
Sponsored by
About this trial
This is an interventional treatment trial for Infertility focused on measuring Assisted reproductive treatment, Superovulation, Follitropin alfa, r-hFSH, AFOLIA
Eligibility Criteria
Inclusion Criteria:
- Age between 20 and 38 years with regular menstrual cycles of 25-35 days
- First or second cycle in the present series of ART
- BMI ≥ 18 ≤ 30 kg/m2
- Basal FSH < 10 IU/L (cycle day 2-5)
- E2 levels < 50pg/mL (< 0.18 nmol/L) at the day of FSH administration
- Antral follicle count (AFC) ≥ 10 to ≤ 25 follicles (sum of both ovaries)
- Infertility due to any of the following factors: tubal factor, mild endometriosis (ASRM stage 1-2), male factor, unexplained infertility
- Presence of both ovaries and normal uterine cavity (confirmed by transvaginal ultrasound within 6 months before randomisation)
- Willingness to participate in the study and to comply with the study protocol
- Informed consent
Exclusion Criteria:
- Presence of pregnancy
- History of ≥2 succeeding ART cycles (IVF and/or ICSI) before the study cycle without clinical pregnancy
- Presence of clinically significant systemic disease
- Presence of chronic cardiovascular, hepatic, renal or pulmonary disease
- Presence of uncontrolled endocrine disorder
- Previous history or presence of severe ovarian hyperstimulation syndrome
- Presence of polycystic ovaries (PCO)
- Presence of severe endometriosis (ASRM stage 3 or stage 4) and hydrosalpinx
- Neoplasia, including tumors of the hypothalamus and pituitary gland
- Abnormal bleeding of undetermined origin
- History of poor response to gonadotropin treatment (defined as fewer than 5 oocytes retrieved in a previous attempt)
- Male infertility without mobile spermatozoa in the ejaculate, that need testicular of epididymal sperm retrieval (MESA/TESE/TESA)
- Endocrine abnormality such as TSH or prolactin level elevations outside the reference range if clinically relevant at screening
- Any hormonal treatment within 1 month before the start of the FSH treatment (with the exception of levothyroxin)
- History of drug, nicotine or alcohol abuse within the last 12 months (> 10 cigarettes/day)
- Administration of other investigational products within the last month
- Clinically abnormal findings at Visit 1
- Planned PGS/PGD/PBB or assisted hatching
- Concomitant participation in an other study protocol
- History of extrauterine pregnancy in the previous 3 months
- Known allergy or hypersensitivity to progesterone or to any of the excipients (including peanut oil) of the additional study medication (GnRH agonist, vitrelle®, and Utrogestan®)
- Presence or history of thrombophlebitis or thromboembolic disorders
- Presence or history of cerebral haemorrhage
- Presence or history of porphyria
Sites / Locations
- Kinderwunsch Institut Schenk GmbH
- Landes-Frauenklinik und Kinderklinik Linz
- AKH Vienna
- IVF Zentrum Döbling
- Privatspital Goldenes Kreuz
- Fertility Clinic
- Copenhagen Fertility Center
- Dansk Fertilitetsklinik
- Universitätsklinikum Bonn
- Universitäts-Frauenklinik
- Institut Universitari Dexeus
- IVI Madrid
- University Hospital of Zurich
- Guy's and St Thomas' NHS Foundation Trust
- Kings College Hospital
- St Barthlomew's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Gonal-f® (Follitropin alfa)
AFOLIA-150 (Follitropin alfa)
Arm Description
Outcomes
Primary Outcome Measures
Number of Oocytes Retrieved (Per Protocol Population)
As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.
The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes
Number of Oocytes Retrieved (Intention-to-treat Population)
As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.
The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes
Secondary Outcome Measures
Number and Size of Follicles ≥ 12 mm at Day 8 of Stimulation
The number and size of follicles 12 mm or over in diameter at day 8 of stimulation were evaluated as secondary end-point.
E2 Concentration at Day 8 and at Day of hCG Administration
The serum concentration of oestradiol was assessed at day 8 and the day of hCG administration.
Total Dose of r-hFSH Administered
Total dose of r-hFSH required was assessed.
Quality of Oocytes Retrieved
Number of patients with ovum pick-up
Fertilisation Rate of Oocytes
Fertilisation rate was assessed
Embryo Quality: Mean Number of Blastomeres
Main embryo quality parameter "mean number of blastomeres"
Number of Participants With Cryopreserved 2PNs, Embryos/Blastocysts
Number of Days of r-hFSH Stimulation
Mean duration of stimulation was assessed.
Number of Patients With Cycle Cancellation
Number of patients with cycle cancellation was assessed.
Number of Patients With Good Response
Good response was defined as "patients with an oocyte retrieval of four or more oocytes"
Implantation Rate
Defined as fetal sac per embryo transferred.
Clinical Pregnancy Rate
Presence of at least one intrauterine gestational sac.
Ongoing Pregnancy
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.
Live Birth Rate
Patients with liveborn children
Embryo Quality: Absence of Multinucleation
Main embryo quality parameter "absence of multinucleation" observed.
Quality of Oocytes Retrieved
Number of patients with transferred blastocysts
Quality of Oocytes Retrieved
Number of embryos per blastocysts transferred
Clinical Pregnancy Rate (Second Treatment Cycle)
Presence of at least one intrauterine gestational sac.
Ongoing Pregnancy (Second Treatment Cycle)
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.
Quality of Oocytes Retrieved
The maturity of the cumulus oophorus was assessed.
Quality of Oocytes Retrieved
The nuclear maturity was assessed (Germinal vesicle, Metaphase I, Metaphase II).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01121666
Brief Title
Multi-centre Study to Compare Efficacy and Safety of AFOLIA and Gonal-f in Women for Assisted Reproductive Treatment
Official Title
A Phase III Assessor-blinded Randomized Parallel Group Multi-centre Study to Compare Efficacy and Safety of Two r-hFSH Formulations (AFOLIA Versus Gonal-f) in Women for Assisted Reproductive Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Finox AG
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Ther purpose of this study is to show equivalence between AFOLIA and Gonal-f® with regard to the number of oocytes retrieved in women for assisted reproductive treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
Assisted reproductive treatment, Superovulation, Follitropin alfa, r-hFSH, AFOLIA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
460 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gonal-f® (Follitropin alfa)
Arm Type
Active Comparator
Arm Title
AFOLIA-150 (Follitropin alfa)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Follitropin alfa
Intervention Description
150IU per day subcutaneously for a maximum of 16 days
Primary Outcome Measure Information:
Title
Number of Oocytes Retrieved (Per Protocol Population)
Description
As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.
The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes
Time Frame
34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
Title
Number of Oocytes Retrieved (Intention-to-treat Population)
Description
As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.
The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes
Time Frame
34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
Secondary Outcome Measure Information:
Title
Number and Size of Follicles ≥ 12 mm at Day 8 of Stimulation
Description
The number and size of follicles 12 mm or over in diameter at day 8 of stimulation were evaluated as secondary end-point.
Time Frame
Day 8 of stimulation
Title
E2 Concentration at Day 8 and at Day of hCG Administration
Description
The serum concentration of oestradiol was assessed at day 8 and the day of hCG administration.
Time Frame
Day 8 of stimulation and at the day of hCG administration (after max. 16 days of r-FSH treatment)
Title
Total Dose of r-hFSH Administered
Description
Total dose of r-hFSH required was assessed.
Time Frame
Day of hCG administration (after maximum 16 days of r-hFSH treatment)
Title
Quality of Oocytes Retrieved
Description
Number of patients with ovum pick-up
Time Frame
34-36 hours after hCG administration
Title
Fertilisation Rate of Oocytes
Description
Fertilisation rate was assessed
Time Frame
1 day after ovum pick-up
Title
Embryo Quality: Mean Number of Blastomeres
Description
Main embryo quality parameter "mean number of blastomeres"
Time Frame
Day 2 of OPU/fertilisation
Title
Number of Participants With Cryopreserved 2PNs, Embryos/Blastocysts
Time Frame
Day 1, 2, 3 and 5 of OPU/fertilisation
Title
Number of Days of r-hFSH Stimulation
Description
Mean duration of stimulation was assessed.
Time Frame
At the day of hCG administration, up to 16 days
Title
Number of Patients With Cycle Cancellation
Description
Number of patients with cycle cancellation was assessed.
Time Frame
Until child birth/miscarriage, up to the end of the study
Title
Number of Patients With Good Response
Description
Good response was defined as "patients with an oocyte retrieval of four or more oocytes"
Time Frame
Until child birth/miscarriage, up to the end of the study
Title
Implantation Rate
Description
Defined as fetal sac per embryo transferred.
Time Frame
Five to six weeks after oocyte retrieval
Title
Clinical Pregnancy Rate
Description
Presence of at least one intrauterine gestational sac.
Time Frame
Five to six weeks after oocyte retrieval
Title
Ongoing Pregnancy
Description
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.
Time Frame
Ten weeks after embryo transfer
Title
Live Birth Rate
Description
Patients with liveborn children
Time Frame
After childbirth with questionnaire
Title
Embryo Quality: Absence of Multinucleation
Description
Main embryo quality parameter "absence of multinucleation" observed.
Time Frame
Day 3
Title
Quality of Oocytes Retrieved
Description
Number of patients with transferred blastocysts
Time Frame
At day 4 and 5
Title
Quality of Oocytes Retrieved
Description
Number of embryos per blastocysts transferred
Time Frame
Day of embryo transfer, either 2, 3 or 5 days after oocyte retrieval
Title
Clinical Pregnancy Rate (Second Treatment Cycle)
Description
Presence of at least one intrauterine gestational sac.
Time Frame
Five to six weeks after oocyte retrieval
Title
Ongoing Pregnancy (Second Treatment Cycle)
Description
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.
Time Frame
10 weeks after embryo transfer
Title
Quality of Oocytes Retrieved
Description
The maturity of the cumulus oophorus was assessed.
Time Frame
After oocyte retrieval, 34 to 36 hours after hCG administration
Title
Quality of Oocytes Retrieved
Description
The nuclear maturity was assessed (Germinal vesicle, Metaphase I, Metaphase II).
Time Frame
After oocyte retrieval, 34 to 36 hours after hCG administration
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
38 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 20 and 38 years with regular menstrual cycles of 25-35 days
First or second cycle in the present series of ART
BMI ≥ 18 ≤ 30 kg/m2
Basal FSH < 10 IU/L (cycle day 2-5)
E2 levels < 50pg/mL (< 0.18 nmol/L) at the day of FSH administration
Antral follicle count (AFC) ≥ 10 to ≤ 25 follicles (sum of both ovaries)
Infertility due to any of the following factors: tubal factor, mild endometriosis (ASRM stage 1-2), male factor, unexplained infertility
Presence of both ovaries and normal uterine cavity (confirmed by transvaginal ultrasound within 6 months before randomisation)
Willingness to participate in the study and to comply with the study protocol
Informed consent
Exclusion Criteria:
Presence of pregnancy
History of ≥2 succeeding ART cycles (IVF and/or ICSI) before the study cycle without clinical pregnancy
Presence of clinically significant systemic disease
Presence of chronic cardiovascular, hepatic, renal or pulmonary disease
Presence of uncontrolled endocrine disorder
Previous history or presence of severe ovarian hyperstimulation syndrome
Presence of polycystic ovaries (PCO)
Presence of severe endometriosis (ASRM stage 3 or stage 4) and hydrosalpinx
Neoplasia, including tumors of the hypothalamus and pituitary gland
Abnormal bleeding of undetermined origin
History of poor response to gonadotropin treatment (defined as fewer than 5 oocytes retrieved in a previous attempt)
Male infertility without mobile spermatozoa in the ejaculate, that need testicular of epididymal sperm retrieval (MESA/TESE/TESA)
Endocrine abnormality such as TSH or prolactin level elevations outside the reference range if clinically relevant at screening
Any hormonal treatment within 1 month before the start of the FSH treatment (with the exception of levothyroxin)
History of drug, nicotine or alcohol abuse within the last 12 months (> 10 cigarettes/day)
Administration of other investigational products within the last month
Clinically abnormal findings at Visit 1
Planned PGS/PGD/PBB or assisted hatching
Concomitant participation in an other study protocol
History of extrauterine pregnancy in the previous 3 months
Known allergy or hypersensitivity to progesterone or to any of the excipients (including peanut oil) of the additional study medication (GnRH agonist, vitrelle®, and Utrogestan®)
Presence or history of thrombophlebitis or thromboembolic disorders
Presence or history of cerebral haemorrhage
Presence or history of porphyria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Imthurn
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kinderwunsch Institut Schenk GmbH
City
Graz
Country
Austria
Facility Name
Landes-Frauenklinik und Kinderklinik Linz
City
Linz
Country
Austria
Facility Name
AKH Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
IVF Zentrum Döbling
City
Vienna
ZIP/Postal Code
11920
Country
Austria
Facility Name
Privatspital Goldenes Kreuz
City
Wien
Country
Austria
Facility Name
Fertility Clinic
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Copenhagen Fertility Center
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Dansk Fertilitetsklinik
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Facility Name
Universitätsklinikum Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Universitäts-Frauenklinik
City
Heidelberg
Country
Germany
Facility Name
Institut Universitari Dexeus
City
Barcelona
ZIP/Postal Code
08028
Country
Spain
Facility Name
IVI Madrid
City
Madrid
ZIP/Postal Code
28023
Country
Spain
Facility Name
University Hospital of Zurich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
Country
United Kingdom
Facility Name
St Barthlomew's Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Multi-centre Study to Compare Efficacy and Safety of AFOLIA and Gonal-f in Women for Assisted Reproductive Treatment
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