search
Back to results

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

Primary Purpose

Infertility

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
AFOLIA
Gonal-f® RFF
Sponsored by
Fertility Biotech AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring IVF, In vitro fertilization, Controlled ovarian stimulation, Follitropin, AFOLIA, Finox

Eligibility Criteria

35 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Physicians Research Group
  • HRC Fertility
  • Reproductive Associates of Delaware
  • FL Fertility Institution
  • Georgia Reproductive Specialists
  • Fertility Centers of Illinois
  • In Via Fertility Specialists
  • Shady Grove Fertility RSC
  • Nevada Center for Reproductive Medicine
  • Cooper Institute of Reproductive Hormonal Disorders, P.C.
  • Institute for Reproductive Health
  • Abington Reproductive Medicine
  • Main Line Fertility Center
  • Shady Grove Fertility RSC, Chesterbrook, PA
  • University of Penn
  • Fertility Associates of Memphis
  • Texas Fertility Center
  • Center for Assisted Reproduction
  • Fertility Specialists of Houston
  • Houston Fertility Institute
  • Center of Reproducitve Medicine
  • Jones Institute for Reproductive Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

AFOLIA

Gonal-f® RFF

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
Number of Oocytes Retrieved - Cycle 1
The number of oocytes retrieved per subject, following hCG administration in Cycle 1.
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.
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
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 3, 2012
Last Updated
October 31, 2017
Sponsor
Fertility Biotech AG
search

1. Study Identification

Unique Protocol Identification Number
NCT01687712
Brief Title
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
November 25, 2013 (Actual)
Primary Completion Date
September 10, 2015 (Actual)
Study Completion Date
November 14, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fertility Biotech AG

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
IVF, In vitro fertilization, Controlled ovarian stimulation, Follitropin, AFOLIA, Finox

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1100 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julian Jenkins, DM FRCOG
Organizational Affiliation
Fertility Biotech AG
Official's Role
Study Director
Facility Information:
Facility Name
Physicians Research Group
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
Facility Name
HRC Fertility
City
Encino
State/Province
California
ZIP/Postal Code
91436
Country
United States
Facility Name
Reproductive Associates of Delaware
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
FL Fertility Institution
City
Tampa
State/Province
Florida
ZIP/Postal Code
33759
Country
United States
Facility Name
Georgia Reproductive Specialists
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Fertility Centers of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60610
Country
United States
Facility Name
In Via Fertility Specialists
City
Hoffman Estate
State/Province
Illinois
ZIP/Postal Code
60169
Country
United States
Facility Name
Shady Grove Fertility RSC
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Nevada Center for Reproductive Medicine
City
Reno
State/Province
Nevada
ZIP/Postal Code
89519
Country
United States
Facility Name
Cooper Institute of Reproductive Hormonal Disorders, P.C.
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Name
Institute for Reproductive Health
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45209
Country
United States
Facility Name
Abington Reproductive Medicine
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Main Line Fertility Center
City
Bryn Mawr
State/Province
Pennsylvania
ZIP/Postal Code
19010
Country
United States
Facility Name
Shady Grove Fertility RSC, Chesterbrook, PA
City
Chesterbrook
State/Province
Pennsylvania
ZIP/Postal Code
19087
Country
United States
Facility Name
University of Penn
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Fertility Associates of Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Texas Fertility Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Center for Assisted Reproduction
City
Bedford
State/Province
Texas
ZIP/Postal Code
75022
Country
United States
Facility Name
Fertility Specialists of Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Facility Name
Houston Fertility Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77063
Country
United States
Facility Name
Center of Reproducitve Medicine
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
Jones Institute for Reproductive Medicine
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs