Clinical trial NCT01121666: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: Assisted reproductive treatment
Superovulation
Follitropin alfa
r-hFSH
AFOLIA
Lead sponsor: Finox AG
Sponsor class: INDUSTRY
First posted: 2010-05-12
Enrollment: 460
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Oocytes Retrieved (Per Protocol Population)
timeFrame: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
measure: Number of Oocytes Retrieved (Intention-to-treat Population)
timeFrame: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
Secondary outcomes:
measure: Number and Size of Follicles ≥ 12 mm at Day 8 of Stimulation
timeFrame: Day 8 of stimulation
measure: E2 Concentration at Day 8 and at Day of hCG Administration
timeFrame: Day 8 of stimulation and at the day of hCG administration (after max. 16 days of r-FSH treatment)
measure: Total Dose of r-hFSH Administered
timeFrame: Day of hCG administration (after maximum 16 days of r-hFSH treatment)
measure: Quality of Oocytes Retrieved
timeFrame: 34-36 hours after hCG administration
measure: Fertilisation Rate of Oocytes
timeFrame: 1 day after ovum pick-up
measure: Embryo Quality: Mean Number of Blastomeres
timeFrame: Day 2 of OPU/fertilisation
measure: Number of Participants With Cryopreserved 2PNs, Embryos/Blastocysts
timeFrame: Day 1, 2, 3 and 5 of OPU/fertilisation
measure: Number of Days of r-hFSH Stimulation
timeFrame: At the day of hCG administration, up to 16 days
measure: Number of Patients With Cycle Cancellation
timeFrame: Until child birth/miscarriage, up to the end of the study
measure: Number of Patients With Good Response
timeFrame: Until child birth/miscarriage, up to the end of the study
measure: Implantation Rate
timeFrame: Five to six weeks after oocyte retrieval
measure: Clinical Pregnancy Rate
timeFrame: Five to six weeks after oocyte retrieval
measure: Ongoing Pregnancy
timeFrame: Ten weeks after embryo transfer
measure: Live Birth Rate
timeFrame: After childbirth with questionnaire
measure: Embryo Quality: Absence of Multinucleation
timeFrame: Day 3
measure: Quality of Oocytes Retrieved
timeFrame: At day 4 and 5
measure: Quality of Oocytes Retrieved
timeFrame: Day of embryo transfer, either 2, 3 or 5 days after oocyte retrieval
measure: Clinical Pregnancy Rate (Second Treatment Cycle)
timeFrame: Five to six weeks after oocyte retrieval
measure: Ongoing Pregnancy (Second Treatment Cycle)
timeFrame: 10 weeks after embryo transfer
measure: Quality of Oocytes Retrieved
timeFrame: After oocyte retrieval, 34 to 36 hours after hCG administration
measure: Quality of Oocytes Retrieved
timeFrame: After oocyte retrieval, 34 to 36 hours after hCG administration
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Kinderwunsch Institut Schenk GmbH
city: Linz
country: Austria
facility: Landes-Frauenklinik und Kinderklinik Linz
city: Vienna
country: Austria
facility: AKH Vienna
city: Vienna
country: Austria
facility: IVF Zentrum Döbling
city: Wien
country: Austria
facility: Privatspital Goldenes Kreuz
city: Copenhagen
country: Denmark
facility: Fertility Clinic
city: Copenhagen
country: Denmark
facility: Copenhagen Fertility Center
city: Frederiksberg
country: Denmark
facility: Dansk Fertilitetsklinik
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Heidelberg
country: Germany
facility: Universitäts-Frauenklinik
city: Barcelona
country: Spain
facility: Institut Universitari Dexeus
city: Madrid
country: Spain
facility: IVI Madrid
city: Zurich
country: Switzerland
facility: University Hospital of Zurich
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: St Barthlomew's Hospital
Study officials:
affiliation: University of Zurich
name: Bruno Imthurn
role: PRINCIPAL_INVESTIGATOR
References: