Clinical trial NCT01687712: Phase III Study Comparing Efficacy and Safety of AFOLIA vs Gonal-f® RFF in Women (35 to 42) Undergoing IVF
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: IVF
In vitro fertilization
Controlled ovarian stimulation
Follitropin
AFOLIA
Finox
Lead sponsor: Fertility Biotech AG
Sponsor class: INDUSTRY
First posted: 2012-09-19
Enrollment: 1100
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population
timeFrame: Six weeks post embryo transfer
measure: Clinical Pregnancy Rate After One Cycle of Treatment - PP Population
timeFrame: Six weeks post embryo transfer
Secondary outcomes:
measure: Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1
timeFrame: Measured at discretionary visits between Days 9 and 15 after FSH starts
measure: Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1
timeFrame: Measured at discretionary visits between Days 9 and 15 after FSH starts.
measure: Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1
timeFrame: Measured at discretionary visits between Days 9 and 15 after FSH starts.
measure: Number of Oocytes Retrieved - Cycle 1
timeFrame: Visit 8, 34-36 hours after hCG administration
measure: Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1
timeFrame: 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).
measure: Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1
timeFrame: 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).
measure: Overall Summary of Adverse Events (AEs) - Cycle 1
timeFrame: 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).
measure: Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1
timeFrame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
measure: Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2
timeFrame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
measure: Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3
timeFrame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
measure: Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1
timeFrame: 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).
measure: Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2
timeFrame: 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).
measure: Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3
timeFrame: 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).
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Physicians Research Group
state: Arizona
city: Encino
country: United States
facility: HRC Fertility
state: California
city: Newark
country: United States
facility: Reproductive Associates of Delaware
state: Delaware
city: Tampa
country: United States
facility: FL Fertility Institution
state: Florida
city: Atlanta
country: United States
facility: Georgia Reproductive Specialists
state: Georgia
city: Chicago
country: United States
facility: Fertility Centers of Illinois
state: Illinois
city: Hoffman Estate
country: United States
facility: In Via Fertility Specialists
state: Illinois
city: Rockville
country: United States
facility: Shady Grove Fertility RSC
state: Maryland
city: Reno
country: United States
facility: Nevada Center for Reproductive Medicine
state: Nevada
city: Marlton
country: United States
facility: Cooper Institute of Reproductive Hormonal Disorders, P.C.
state: New Jersey
city: Cincinnati
country: United States
facility: Institute for Reproductive Health
state: Ohio
city: Abington
country: United States
facility: Abington Reproductive Medicine
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Main Line Fertility Center
state: Pennsylvania
city: Chesterbrook
country: United States
facility: Shady Grove Fertility RSC, Chesterbrook, PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Penn
state: Pennsylvania
city: Memphis
country: United States
facility: Fertility Associates of Memphis
state: Tennessee
city: Austin
country: United States
facility: Texas Fertility Center
state: Texas
city: Bedford
country: United States
facility: Center for Assisted Reproduction
state: Texas
city: Houston
country: United States
facility: Fertility Specialists of Houston
state: Texas
city: Houston
country: United States
facility: Houston Fertility Institute
state: Texas
city: Webster
country: United States
facility: Center of Reproducitve Medicine
state: Texas
city: Norfolk
country: United States
facility: Jones Institute for Reproductive Medicine
state: Virginia
Study officials:
affiliation: Fertility Biotech AG
name: Julian Jenkins, DM FRCOG
role: STUDY_DIRECTOR
References: