Multi-centre Study to Compare Efficacy and Safety of AFOLIA and Gonal-f in Women for Assisted Reproductive Treatment

Phase 3

Completed

• Conditions: Infertility
• Interventions: Drug: Follitropin alfa

• Registration Number: NCT01121666
• Lead Sponsor: Finox AG

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-05-10
• Study First Submitted QC: 2010-05-11
• Study First Posted: 2010-05-12
• Study Start: 2010-06
• Primary Completion: 2011-12
• Study Completion: 2013-03
• Results First Submitted: 2016-02-17
• Status Verified: 2016-03
• Results First Submitted QC: 2016-03-16
• Last Update Submitted: 2016-03-16
• Results First Posted: 2016-04-15
• Last Update Posted: 2016-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 460

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gonal-f® (Follitropin alfa)	Follitropin alfa	-
AFOLIA-150 (Follitropin alfa)	Follitropin alfa	-

Primary Outcome Measures

Name	Time	Method
Number of Oocytes Retrieved (Per Protocol Population)	34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment	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)	34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment	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

Name	Time	Method
Number and Size of Follicles ≥ 12 mm at Day 8 of Stimulation	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	Day 8 of stimulation and at the day of hCG administration (after max. 16 days of r-FSH treatment)	The serum concentration of oestradiol was assessed at day 8 and the day of hCG administration.
Total Dose of r-hFSH Administered	Day of hCG administration (after maximum 16 days of r-hFSH treatment)	Total dose of r-hFSH required was assessed.
Quality of Oocytes Retrieved	After oocyte retrieval, 34 to 36 hours after hCG administration	The nuclear maturity was assessed (Germinal vesicle, Metaphase I, Metaphase II).
Fertilisation Rate of Oocytes	1 day after ovum pick-up	Fertilisation rate was assessed
Embryo Quality: Mean Number of Blastomeres	Day 2 of OPU/fertilisation	Main embryo quality parameter "mean number of blastomeres"
Number of Participants With Cryopreserved 2PNs, Embryos/Blastocysts	Day 1, 2, 3 and 5 of OPU/fertilisation
Number of Days of r-hFSH Stimulation	At the day of hCG administration, up to 16 days	Mean duration of stimulation was assessed.
Number of Patients With Cycle Cancellation	Until child birth/miscarriage, up to the end of the study	Number of patients with cycle cancellation was assessed.
Number of Patients With Good Response	Until child birth/miscarriage, up to the end of the study	Good response was defined as "patients with an oocyte retrieval of four or more oocytes"
Implantation Rate	Five to six weeks after oocyte retrieval	Defined as fetal sac per embryo transferred.
Clinical Pregnancy Rate	Five to six weeks after oocyte retrieval	Presence of at least one intrauterine gestational sac.
Ongoing Pregnancy	Ten weeks after embryo transfer	Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.
Live Birth Rate	After childbirth with questionnaire	Patients with liveborn children
Embryo Quality: Absence of Multinucleation	Day 3	Main embryo quality parameter "absence of multinucleation" observed.
Clinical Pregnancy Rate (Second Treatment Cycle)	Five to six weeks after oocyte retrieval	Presence of at least one intrauterine gestational sac.
Ongoing Pregnancy (Second Treatment Cycle)	10 weeks after embryo transfer	Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.

Trial Locations

Locations (16)

Privatspital Goldenes Kreuz; 🇦🇹 Wien, Austria

IVF Zentrum Döbling; 🇦🇹 Vienna, Austria

University Hospital of Zurich; 🇨🇭 Zurich, Switzerland

Kinderwunsch Institut Schenk GmbH; 🇦🇹 Graz, Austria

Landes-Frauenklinik und Kinderklinik Linz; 🇦🇹 Linz, Austria

AKH Vienna; 🇦🇹 Vienna, Austria

Fertility Clinic; 🇩🇰 Copenhagen, Denmark

Copenhagen Fertility Center; 🇩🇰 Copenhagen, Denmark

Dansk Fertilitetsklinik; 🇩🇰 Frederiksberg, Denmark

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Institut Universitari Dexeus; 🇪🇸 Barcelona, Spain

Universitäts-Frauenklinik; 🇩🇪 Heidelberg, Germany

Kings College Hospital; 🇬🇧 London, United Kingdom

IVI Madrid; 🇪🇸 Madrid, Spain

St Barthlomew's Hospital; 🇬🇧 London, United Kingdom

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom