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

Infertility Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01687712
• Other study ID #: FIN3002
• Status: Completed
• Phase: Phase 3
• First received: September 3, 2012
• Last updated: October 31, 2017
• Start date: November 25, 2013
• Est. completion date: November 14, 2016

Study information

• Verified date: October 2017
• Source: Fertility Biotech AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1100
• Est. completion date: November 14, 2016
• Est. primary completion date: September 10, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Abington Reproductive Medicine	Abington	Pennsylvania
United States	Georgia Reproductive Specialists	Atlanta	Georgia
United States	Texas Fertility Center	Austin	Texas
United States	Center for Assisted Reproduction	Bedford	Texas
United States	Main Line Fertility Center	Bryn Mawr	Pennsylvania
United States	Shady Grove Fertility RSC, Chesterbrook, PA	Chesterbrook	Pennsylvania
United States	Fertility Centers of Illinois	Chicago	Illinois
United States	Institute for Reproductive Health	Cincinnati	Ohio
United States	HRC Fertility	Encino	California
United States	In Via Fertility Specialists	Hoffman Estate	Illinois
United States	Fertility Specialists of Houston	Houston	Texas
United States	Houston Fertility Institute	Houston	Texas
United States	Cooper Institute of Reproductive Hormonal Disorders, P.C.	Marlton	New Jersey
United States	Fertility Associates of Memphis	Memphis	Tennessee
United States	Reproductive Associates of Delaware	Newark	Delaware
United States	Jones Institute for Reproductive Medicine	Norfolk	Virginia
United States	University of Penn	Philadelphia	Pennsylvania
United States	Nevada Center for Reproductive Medicine	Reno	Nevada
United States	Shady Grove Fertility RSC	Rockville	Maryland
United States	FL Fertility Institution	Tampa	Florida
United States	Physicians Research Group	Tempe	Arizona
United States	Center of Reproducitve Medicine	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Fertility Biotech AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population	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.	Six weeks post embryo transfer
Primary	Clinical Pregnancy Rate After One Cycle of Treatment - PP Population	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.	Six weeks post embryo transfer
Secondary	Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1	The number of days of r-hFSH stimulation a subject received during Cycle 1.	Measured at discretionary visits between Days 9 and 15 after FSH starts
Secondary	Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1	The total dose of r-hFSH that subjects received during Cycle 1.	Measured at discretionary visits between Days 9 and 15 after FSH starts.
Secondary	Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1	The mean dose of r-hFSH that subjects received in a day during Cycle 1.	Measured at discretionary visits between Days 9 and 15 after FSH starts.
Secondary	Number of Oocytes Retrieved - Cycle 1	The number of oocytes retrieved per subject, following hCG administration in Cycle 1.	Visit 8, 34-36 hours after hCG administration
Secondary	Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1	Number of subjects reporting at least one dermal response to r-hFSH injection and number of subjects reporting no dermal responses.	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).
Secondary	Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1	Dermal response to r-hFSH injection as assessed by the investigator and categorized according to severity of reaction	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).
Secondary	Overall Summary of Adverse Events (AEs) - Cycle 1	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	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).
Secondary	Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1	Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.	Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Secondary	Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2	Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.	Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Secondary	Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3	Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included.	Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
Secondary	Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1	Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 1.	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).
Secondary	Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2	Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 2.	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).
Secondary	Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3	Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 3.	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).