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Phase III Study Comparing Efficacy and Safety of AFOLIA vs Gonal-f® RFF in Women (35 to 42) Undergoing IVF

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01687712
First Posted: September 19, 2012
Last Update Posted: December 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Fertility Biotech AG
  Purpose
The purpose of this study is to show that AFOLIA, a recombinant manufactured human follicle stimulating hormone (r-hFSH) has a similar efficacy and safety profile compared to Gonal-f® RFF.

Condition Intervention Phase
Infertility Drug: AFOLIA Drug: Gonal-f® RFF Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Investigator and Assessor Blinded 1:1 Randomized, Parallel-group Multicenter Study to Compare Efficacy and Safety of Two r-hFSH Formulations (AFOLIA vs Gonal-f® RFF) in Normal Ovulatory Women 35 to 42 Years Old Undergoing in Vitro Fertilization

Further study details as provided by Fertility Biotech AG:

Primary Outcome Measures:
  • Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population [ Time Frame: Six weeks post embryo transfer ]
    Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the ITT population of the respective treatment arm.

  • Clinical Pregnancy Rate After One Cycle of Treatment - PP Population [ Time Frame: Six weeks post embryo transfer ]
    Clinical pregnancy was defined as presence of at least one intrauterine gestational sac and fetal heart activity as demonstrated by vaginal ultrasound at six weeks (42 +/- 1 day) post ET (Visit 11). The clinical pregnancy rate is the proportion of subjects who achieve clinical pregnancy, relative to the number of patients in the PP population of the respective treatment arm.


Secondary Outcome Measures:
  • Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1 [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts ]
    The number of days of r-hFSH stimulation a subject received during Cycle 1.

  • Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1 [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts. ]
    The total dose of r-hFSH that subjects received during Cycle 1.

  • Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1 [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts. ]
    The mean dose of r-hFSH that subjects received in a day during Cycle 1.

  • Number of Oocytes Retrieved - Cycle 1 [ Time Frame: Visit 8, 34-36 hours after hCG administration ]
    The number of oocytes retrieved per subject, following hCG administration in Cycle 1.

  • Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1 [ Time Frame: Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH Start through to Day 16 after start of FSH (16 days). ]
    Number of subjects reporting at least one dermal response to r-hFSH injection and number of subjects reporting no dermal responses.

  • Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1 [ Time Frame: Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH through to Day 16 after start of FSH (16 days). ]
    Dermal response to r-hFSH injection as assessed by the investigator and categorized according to severity of reaction

  • Overall Summary of Adverse Events (AEs) - Cycle 1 [ Time Frame: Measured from the start of FSH treatment through to either the end FSH treatment + 30 days (up to 46 days) or to the last Telephone Follow-up / Live Birth Questionnaire on pregnancy outcome (if applicable) (up to 10 months). ]

    Summary of AEs, including the number of subjects experiencing to following during Cycle 1:

    At least one AE At least one treatment related AE At least one serious AE At least one AE leading to discontinuation of study drug At least one AE due to pregnancy complication


  • Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1 [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]
    Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.

  • Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2 [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]
    Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.

  • Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3 [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]
    Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.

  • Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1 [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]
    Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 1.

  • Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2 [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]
    Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 2.

  • Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3 [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]
    Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 3.


Enrollment: 1100
Actual Study Start Date: November 25, 2013
Study Completion Date: November 14, 2016
Primary Completion Date: September 10, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AFOLIA
One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Drug: AFOLIA
225IU subcutaneously, starting at the day of successful down-regulation for the first 5 days, followed by a treatment period with an increased dose until the point of ovulation induction has been reached
Other Name: Follitropin-alfa
Active Comparator: Gonal-f® RFF
One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Drug: Gonal-f® RFF
225IU subcutaneously, starting at the day of successful down-regulation for the first 5 days, followed by a treatment period with an increased dose until the point of ovulation induction has been reached
Other Name: Follitropin-alfa

Detailed Description:
Comparison of the clinical pregnancy rate in the AFOLIA group compared to the US approved Gonal-f® RFF Redi-ject group as the primary endpoint. Comparison of the number and size of follicles, the number of cycle cancellation, the hormone parameters and adverse events in the AFOLIA group compared to the Gonal-f® RFF group as secondary endpoints.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 35 to 42 years of age
  • Indication for controlled ovarian stimulation and IVF or intracytoplasmic sperm injection (ICSI)
  • Regular menstrual cycles (25-35 days)
  • History of a maximum of two fresh cycle treatments in the present series of assisted reproductive technologies (ART) at the day of first screening (thawed cycles are not subject to that criteria)
  • Body mass index (BMI) ≥18 and ≤38 kg/m2
  • Basal FSH <12 IU/L (cycle day 2-5)
  • Antral follicle count (AFC) ≥ 10 to ≤20 follicles with a diameter of <11mm (sum of both ovaries) as measured on ultrasound (US) in the early follicular phase (menstrual cycle day 2-5)
  • Documented history of infertility due to any of the following factors: tubal factor, mild endometriosis (American Society for Reproductive Medicine [ASRM] stage 1-2), male factor, unexplained infertility
  • Presence of both ovaries by ultrasonography and normal uterine cavity (confirmed by hysterosalpingography, saline infusion sonography or hysteroscopy within 6 months before randomization)
  • Male partner with semen analysis that is at least adequate for ICSI within 6 months prior to patient beginning down-regulation (invasive or surgical sperm retrieval, donor and/or cryopreserved sperm may be used)
  • Willingness to participate in the study and to comply with the study protocol
  • Signed informed consent prior to screening

Exclusion Criteria:

  • Presence of pregnancy
  • History of or active polycystic ovary syndrome (PCOS)
  • AFC >20 follicles with a diameter of <11 mm (both ovaries combined) as measured on US in the early follicular phase (menstrual cycle day 2-5)
  • History of >2 unsuccessful fresh ART retrieval cycles
  • Presence of uncontrolled endocrine disorder
  • Previous history or presence of severe OHSS
  • Intrauterine fibroids ≥5 cm or otherwise clinically relevant pathology that could impair embryo implantation or pregnancy continuation
  • History of recurrent spontaneous abortion (3 or more, even when unexplained)
  • Presence of severe endometriosis (ASRM stage 3 or stage 4) or hydrosalpinx
  • Neoplasia, including tumors of the hypothalamus and pituitary gland
  • Abnormal bleeding of undetermined origin
  • 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 medications (GnRH agonist, Ovidrel®, and Crinone 8%®)
  • History of poor response to gonadotropin treatment (defined as fewer than 5 oocytes retrieved in a previous attempt)
  • Any hormonal treatment within 1 month before the start of the FSH treatment, with the exception of levothyroxine)
  • Egg donor
  • Administration of other investigational products within the previous month
  • Clinically abnormal findings at Visit 1
  • Concomitant participation in another study protocol
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01687712


Locations
United States, Arizona
Physicians Research Group
Tempe, Arizona, United States, 85284
United States, California
HRC Fertility
Encino, California, United States, 91436
United States, Delaware
Reproductive Associates of Delaware
Newark, Delaware, United States, 19713
United States, Florida
FL Fertility Institution
Tampa, Florida, United States, 33759
United States, Georgia
Georgia Reproductive Specialists
Atlanta, Georgia, United States, 30342
United States, Illinois
Fertility Centers of Illinois
Chicago, Illinois, United States, 60610
In Via Fertility Specialists
Hoffman Estate, Illinois, United States, 60169
United States, Maryland
Shady Grove Fertility RSC
Rockville, Maryland, United States, 20850
United States, Nevada
Nevada Center for Reproductive Medicine
Reno, Nevada, United States, 89519
United States, New Jersey
Cooper Institute of Reproductive Hormonal Disorders, P.C.
Marlton, New Jersey, United States, 08053
United States, Ohio
Institute for Reproductive Health
Cincinnati, Ohio, United States, 45209
United States, Pennsylvania
Abington Reproductive Medicine
Abington, Pennsylvania, United States, 19001
Main Line Fertility Center
Bryn Mawr, Pennsylvania, United States, 19010
Shady Grove Fertility RSC, Chesterbrook, PA
Chesterbrook, Pennsylvania, United States, 19087
University of Penn
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Fertility Associates of Memphis
Memphis, Tennessee, United States, 38120
United States, Texas
Texas Fertility Center
Austin, Texas, United States, 78731
Center for Assisted Reproduction
Bedford, Texas, United States, 75022
Fertility Specialists of Houston
Houston, Texas, United States, 77054
Houston Fertility Institute
Houston, Texas, United States, 77063
Center of Reproducitve Medicine
Webster, Texas, United States, 77598
United States, Virginia
Jones Institute for Reproductive Medicine
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Fertility Biotech AG
Investigators
Study Director: Julian Jenkins, DM FRCOG Fertility Biotech AG
  More Information

Responsible Party: Fertility Biotech AG
ClinicalTrials.gov Identifier: NCT01687712     History of Changes
Other Study ID Numbers: FIN3002
First Submitted: September 3, 2012
First Posted: September 19, 2012
Results First Submitted: September 20, 2017
Results First Posted: October 18, 2017
Last Update Posted: December 5, 2017
Last Verified: October 2017

Keywords provided by Fertility Biotech AG:
IVF
In vitro fertilization
Controlled ovarian stimulation
Follitropin
AFOLIA
Finox

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