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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Finox AG
ClinicalTrials.gov Identifier:
NCT01121666
First received: May 10, 2010
Last updated: March 16, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Infertility
Drug: Follitropin alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: 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

Further study details as provided by Finox AG:

Primary Outcome Measures:
  • Number of Oocytes Retrieved (Per Protocol Population) [ Time Frame: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment ] [ Designated as safety issue: No ]

    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) [ Time Frame: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 8 of stimulation ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 8 of stimulation and at the day of hCG administration (after max. 16 days of r-FSH treatment) ] [ Designated as safety issue: No ]
    The serum concentration of oestradiol was assessed at day 8 and the day of hCG administration.

  • Total Dose of r-hFSH Administered [ Time Frame: Day of hCG administration (after maximum 16 days of r-hFSH treatment) ] [ Designated as safety issue: No ]
    Total dose of r-hFSH required was assessed.

  • Quality of Oocytes Retrieved [ Time Frame: 34-36 hours after hCG administration ] [ Designated as safety issue: No ]
    Number of patients with ovum pick-up

  • Fertilisation Rate of Oocytes [ Time Frame: 1 day after ovum pick-up ] [ Designated as safety issue: No ]
    Fertilisation rate was assessed

  • Embryo Quality: Mean Number of Blastomeres [ Time Frame: Day 2 of OPU/fertilisation ] [ Designated as safety issue: No ]
    Main embryo quality parameter "mean number of blastomeres"

  • Number of Participants With Cryopreserved 2PNs, Embryos/Blastocysts [ Time Frame: Day 1, 2, 3 and 5 of OPU/fertilisation ] [ Designated as safety issue: No ]
  • Number of Days of r-hFSH Stimulation [ Time Frame: At the day of hCG administration, up to 16 days ] [ Designated as safety issue: No ]
    Mean duration of stimulation was assessed.

  • Number of Patients With Cycle Cancellation [ Time Frame: Until child birth/miscarriage, up to the end of the study ] [ Designated as safety issue: No ]
    Number of patients with cycle cancellation was assessed.

  • Number of Patients With Good Response [ Time Frame: Until child birth/miscarriage, up to the end of the study ] [ Designated as safety issue: No ]
    Good response was defined as "patients with an oocyte retrieval of four or more oocytes"

  • Implantation Rate [ Time Frame: Five to six weeks after oocyte retrieval ] [ Designated as safety issue: No ]
    Defined as fetal sac per embryo transferred.

  • Clinical Pregnancy Rate [ Time Frame: Five to six weeks after oocyte retrieval ] [ Designated as safety issue: No ]
    Presence of at least one intrauterine gestational sac.

  • Ongoing Pregnancy [ Time Frame: Ten weeks after embryo transfer ] [ Designated as safety issue: No ]
    Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.

  • Live Birth Rate [ Time Frame: After childbirth with questionnaire ] [ Designated as safety issue: No ]
    Patients with liveborn children

  • Embryo Quality: Absence of Multinucleation [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Main embryo quality parameter "absence of multinucleation" observed.

  • Quality of Oocytes Retrieved [ Time Frame: At day 4 and 5 ] [ Designated as safety issue: No ]
    Number of patients with transferred blastocysts

  • Quality of Oocytes Retrieved [ Time Frame: Day of embryo transfer, either 2, 3 or 5 days after oocyte retrieval ] [ Designated as safety issue: No ]
    Number of embryos per blastocysts transferred

  • Clinical Pregnancy Rate (Second Treatment Cycle) [ Time Frame: Five to six weeks after oocyte retrieval ] [ Designated as safety issue: No ]
    Presence of at least one intrauterine gestational sac.

  • Ongoing Pregnancy (Second Treatment Cycle) [ Time Frame: 10 weeks after embryo transfer ] [ Designated as safety issue: No ]
    Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer.

  • Quality of Oocytes Retrieved [ Time Frame: After oocyte retrieval, 34 to 36 hours after hCG administration ] [ Designated as safety issue: No ]
    The maturity of the cumulus oophorus was assessed.

  • Quality of Oocytes Retrieved [ Time Frame: After oocyte retrieval, 34 to 36 hours after hCG administration ] [ Designated as safety issue: No ]
    The nuclear maturity was assessed (Germinal vesicle, Metaphase I, Metaphase II).


Enrollment: 460
Study Start Date: June 2010
Study Completion Date: March 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gonal-f® (Follitropin alfa) Drug: Follitropin alfa
150IU per day subcutaneously for a maximum of 16 days
Experimental: AFOLIA-150 (Follitropin alfa) Drug: Follitropin alfa
150IU per day subcutaneously for a maximum of 16 days

  Eligibility

Ages Eligible for Study:   20 Years to 38 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121666

Locations
Austria
Kinderwunsch Institut Schenk GmbH
Graz, Austria
Landes-Frauenklinik und Kinderklinik Linz
Linz, Austria
AKH Vienna
Vienna, Austria, 1090
IVF Zentrum Döbling
Vienna, Austria, 11920
Privatspital Goldenes Kreuz
Wien, Austria
Denmark
Fertility Clinic
Copenhagen, Denmark, 2100
Copenhagen Fertility Center
Copenhagen, Denmark, 2400
Dansk Fertilitetsklinik
Frederiksberg, Denmark, 2000
Germany
Universitätsklinikum Bonn
Bonn, Germany, 53105
Universitäts-Frauenklinik
Heidelberg, Germany
Spain
Institut Universitari Dexeus
Barcelona, Spain, 08028
IVI Madrid
Madrid, Spain, 28023
Switzerland
University Hospital of Zurich
Zurich, Switzerland, 8091
United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom, SE1 9RT
Kings College Hospital
London, United Kingdom
St Barthlomew's Hospital
London, United Kingdom
Sponsors and Collaborators
Finox AG
Investigators
Principal Investigator: Bruno Imthurn University of Zurich
  More Information

Responsible Party: Finox AG
ClinicalTrials.gov Identifier: NCT01121666     History of Changes
Other Study ID Numbers: FIN3001  2010-019287-37 
Study First Received: May 10, 2010
Results First Received: February 17, 2016
Last Updated: March 16, 2016
Health Authority: Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic
Denmark: Danish Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Finox AG:
Assisted reproductive treatment
Superovulation
Follitropin alfa
r-hFSH
AFOLIA

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Follicle Stimulating Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016