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

NCT01687712 | Completed Phase 3 Results

• 1 other identifier: FIN3002
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 22

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.

Conditions

Infertility

Keywords

IVF; In vitro fertilization; Controlled ovarian stimulation; Follitropin; AFOLIA; Finox

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (13)

• Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1

  Measured at discretionary visits between Days 9 and 15 after FSH starts

• Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1

  Measured at discretionary visits between Days 9 and 15 after FSH starts.

• Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1

  Measured at discretionary visits between Days 9 and 15 after FSH starts.

• Number of Oocytes Retrieved - Cycle 1

  Visit 8, 34-36 hours after hCG administration

• Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1

  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).

Study Arms (2)

AFOLIA

EXPERIMENTAL

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

Gonal-f® RFF

ACTIVE COMPARATOR

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

Interventions

AFOLIA DRUG

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

Also known as: Follitropin-alfa

AFOLIA

Gonal-f® RFF DRUG

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

Also known as: Follitropin-alfa

Gonal-f® RFF

Eligibility Criteria

• Age: 35 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fertility Biotech AG: lead

Study Sites (22)

Physicians Research Group

Tempe, Arizona, 85284, United States

Location

HRC Fertility

Encino, California, 91436, United States

Location

Reproductive Associates of Delaware

Newark, Delaware, 19713, United States

Location

FL Fertility Institution

Tampa, Florida, 33759, United States

Location

Georgia Reproductive Specialists

Atlanta, Georgia, 30342, United States

Location

Fertility Centers of Illinois

Chicago, Illinois, 60610, United States

Location

In Via Fertility Specialists

Hoffman Estate, Illinois, 60169, United States

Location

Shady Grove Fertility RSC

Rockville, Maryland, 20850, United States

Location

Nevada Center for Reproductive Medicine

Reno, Nevada, 89519, United States

Location

Cooper Institute of Reproductive Hormonal Disorders, P.C.

Marlton, New Jersey, 08053, United States

Location

Institute for Reproductive Health

Cincinnati, Ohio, 45209, United States

Location

Abington Reproductive Medicine

Abington, Pennsylvania, 19001, United States

Location

Main Line Fertility Center

Bryn Mawr, Pennsylvania, 19010, United States

Location

Shady Grove Fertility RSC, Chesterbrook, PA

Chesterbrook, Pennsylvania, 19087, United States

Location

University of Penn

Philadelphia, Pennsylvania, 19104, United States

Location

Fertility Associates of Memphis

Memphis, Tennessee, 38120, United States

Location

Texas Fertility Center

Austin, Texas, 78731, United States

Location

Center for Assisted Reproduction

Bedford, Texas, 75022, United States

Location

Fertility Specialists of Houston

Houston, Texas, 77054, United States

Location

Houston Fertility Institute

Houston, Texas, 77063, United States

Location

Center of Reproducitve Medicine

Webster, Texas, 77598, United States

Location

Jones Institute for Reproductive Medicine

Norfolk, Virginia, 23507, United States

Location

MeSH Terms

Conditions

Infertility

Interventions

Glycoprotein Hormones, alpha Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chorionic Gonadotropin; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Executive VP of Regulatory Affairs
• Organization: Fertility Biotech AG

maria.vazquez@fertilitybiotech.com

Study Officials

• Julian Jenkins, DM FRCOG

  Fertility Biotech AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2012
• First Posted: September 19, 2012
• Study Start: November 25, 2013
• Primary Completion: September 10, 2015
• Study Completion: November 14, 2016
• Last Updated: December 5, 2017
• Results First Posted: October 18, 2017

Record last verified: 2017-10

Locations

US (22)