Evaluation of Efficacy and Safety of Highly Purified Urofollitropin in Chinese Females Undergoing an Assisted Reproductive Technology (ART) Program

• ClinicalTrials.gov Identifier: NCT01922193
• Recruitment Status: Completed
• First Posted: August 14, 2013
• Last Update Posted: June 16, 2015
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

Tracking Information

• First Submitted Date: July 24, 2013
• First Posted Date: August 14, 2013
• Last Update Posted Date: June 16, 2015
• Study Start Date: October 2013
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 13, 2013): The number of retrieved oocytes per cycle [ Time Frame: About 36 hours post hCG (human chorionic gonadotrophin) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 23, 2013)

• The follicles development [ Time Frame: At day 5 of FSH preparation stimulation and the day of hCG administration ]
• The fertilization rate [ Time Frame: 20h (± 1h) after insemination ]
• Implantation rate [ Time Frame: 5-6 weeks post embryo transfer ]
• Cycle cancellation rate [ Time Frame: 36 hours post hCG ]
• The positive serum β-hCG/hCG rate [ Time Frame: 13-15 days after embryo transfer ]
• The clinical pregnancy rate [ Time Frame: 5-6 weeks after embryo transfer ]
  Regardless of fetal heart beat
• The clinical pregnancy rate [ Time Frame: 5-6 weeks after embryo transfer ]
  With fetal heart beat
• The ongoing pregnancy rate [ Time Frame: 10-11 weeks after embryo transfer ]
• Total gonadotropin dose administered and the duration of gonadotropin treatment [ Time Frame: Up to day 16 (in the stimulation period) ]
• Serum E2 (Estradiol) concentrations [ Time Frame: On the day of hCG administration ]
• Frequency and severity of adverse events [ Time Frame: Expected maximum of 7 months ]
• Frequency and severity of injection site reactions [ Time Frame: Day 1 up to day 16 of the controlled ovarian stimulation period ]
  Injection site reactions (in terms of "redness", "pain", "itching", "swelling" and "bruising")

Original Secondary Outcome Measures (submitted: August 13, 2013)

• The follicles development [ Time Frame: At day 5 of FSH preparation stimulation and the day of hCG administration ]
• The fertilization rate [ Time Frame: 20h (± 1h) after insemination ]
• Implantation rate [ Time Frame: 5-6 weeks post embryo transfer ]
• Cycle cancellation rate [ Time Frame: 36 hours post hCG ]
• The positive serum β-hCG rate [ Time Frame: 13-15 days after embryo transfer ]
• The clinical pregnancy rate [ Time Frame: 5-6 weeks after embryo transfer ]
  Regardless of fetal heart beat
• The clinical pregnancy rate [ Time Frame: 5-6 weeks after embryo transfer ]
  With fetal heart beat
• The ongoing pregnancy rate [ Time Frame: 10-11 weeks after embryo transfer ]
• Total gonadotropin dose administered and the duration of gonadotropin treatment [ Time Frame: Up to day 16 (in the stimulation period) ]
• Serum E2 (Estradiol) concentrations [ Time Frame: On the day of hCG administration ]
• Frequency and severity of adverse events [ Time Frame: Expected maximum of 7 months ]
• Frequency and severity of injection site reactions [ Time Frame: Day 1-5 of the controlled ovarian stimulation period ]
  Injection site reactions (in terms of "redness", "pain", "itching", "swelling" and "bruising")

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Efficacy and Safety of Highly Purified Urofollitropin in Chinese Females Undergoing an Assisted Reproductive Technology (ART) Program
• Official Title: A Randomized, Assessor-blinded, Parallel Group, Multi-center, Non-inferiority Study Investigating the Efficacy and Safety of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection in Controlled Ovarian Stimulation in Chinese Females Undergoing an Assisted Reproductive Technology (ART) Program
• Brief Summary: Evaluate the efficacy and safety of of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection in Chinese Females Undergoing an Assisted Reproductive Technology (ART) Program.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Infertility

Intervention

• Drug: Highly Purified Urofollitropin
  for injection
  Other Name: Bravelle®
• Drug: Recombinant Human Follitropin Alfa
  for injection
  Other Name: Gonal-F®

Study Arms

• Experimental: Test Group
  Intervention: Drug: Highly Purified Urofollitropin
• Active Comparator: Control Group
  Intervention: Drug: Recombinant Human Follitropin Alfa

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 26, 2015): 263
• Original Estimated Enrollment (submitted: August 13, 2013): 200
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent form, prior to screening evaluations
• In good physical and mental health
• Chinese Females between the ages of 20-39 years.
• Body mass index (BMI) is ≥ 18.5 and < 28 kg/m2
• Female diagnosed for at least one year (i.e., before screening) with tubal infertility, unexplained infertility, male factor infertility
• Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory

• Documented evidence of at least one of the following within ninety (90) days prior to down regulation treatment:

  • mid-luteal phase serum progesterone level > 5ng/mL, or
  • late luteal phase endometrial biopsy with < 3 days lag, or
  • biphasic basal body temperature chart, or
  • mid-cycle urinary LH (Luteinizing hormone)surge
• Early follicular phase (day 2-3), serum levels of FSH within limits (1-12IU/L)(results obtained within 90 days prior to down regulation treatment)
• LH, PRL (prolactin), E2 (Estradiol), P (progesterone), total testosterone levels within normal range for the clinical laboratory or considered not clinically significant by the investigator (results obtained within 90 days prior to down regulation treatment)
• TSH (thyrotropin) levels within normal limits for the clinical laboratory or considered not clinically significant by the investigator, or secondary to exogenous thyroid medication (results obtained within 90 days prior to down regulation treatment)
• Negative serum Human Immunodeficiency Virus (HIV) antibody, and TPPA (Treponema Pallidum antibodies)/ RPR (Rapid Plasma Reagin) tests (results obtained within 90 days prior to down regulation treatment)
• Early follicular phase total antral follicle (diameter 2-10 mm) count ≥ 6 and ≤ 25 for both ovaries combined (results obtained within 3 months prior to down regulation treatment)
• Transvaginal ultrasound documenting presence and adequate visualisation of both ovaries, uterus and adnexa without evidence of significant abnormality (e.g.no endometrioma greater than 3 cm, no ovarian cysts > 35 mm or enlarged ovaries which would contraindicate the use of down regulation treatment, no hydrosalpinx) within ninety (90) days prior to down regulation treatment
• Hysterosalpingography, hysteroscopy, saline infusion sonography or transvaginal ultrasound documenting a uterus consistent with expected normal function (e.g.no evidence of clinically interfering uterine fibroids defined as submucous or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are incompatible with pregnancy) within 1 year prior to down regulation treatment. This also includes women who have been diagnosed with any of the above medical conditions but have had them surgically corrected.
• A minimum of one cycle without treatment with fertility modifiers (e.g., oral contraceptives) during the last menstrual cycle before down regulation treatment
• Willing to accept a maximum of two embryos transferred in the fresh cycle
• Willing to use an adequate barrier method of contraception or refrain from intercourse from 2 weeks before start of down regulation and throughout the down regulation period

Exclusion Criteria:

• Any pregnancy within last three (3) months prior to screening
• Known past or current thrombophlebitis or thromboembolism including venous thrombosis disease and active or recent arterial thrombosis disease
• Three or more controlled ovarian stimulation cycles for IVF/ICSI (In vitro fertilization/Intracytoplasmic sperm injection) prior to screening
• Previous IVF or ART failure related to a sperm/fertilization problem which resulted in unsuccessful fertilization and no related medical conditions improved
• Known history of poor ovarian response in a previous controlled ovarian stimulation cycle for IVF/ICSI
• Known history of excessive ovarian response in a previous controlled ovarian stimulation cycle for IVF/ICSI
• Known severe OHSS (Ovarian hyperstimulating syndrome) in a previous controlled ovarian stimulation cycle.
• Known history of polycystic ovary disease (PCOD) associated with anovulation
• Known endometriosis
• Known abnormal results of cervical examination of clinical significance obtained within 1 year prior to screening
• Abnormal vaginal bleeding of undetermined origin
• Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus
• Known current active pelvic inflammatory disease
• Known history of recurrent miscarriage
• Known malformations of the sexual organs incompatible with pregnancy
• According to the judgment of the investigator, abnormal laboratory value of renal or hepatic function is clinically significant
• Known current (3 months prior to screening) or past (1 year prior to screening) abuse of alcohol or drugs, and/or current or past smoking habit of more than 10 cigarettes per day
• Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) which can compromise participation in the trial with the exception of controlled thyroid function disease
• Known history of chemotherapy (except for gestational conditions) or radiotherapy
• According to the judgment of the investigator, abnormal laboratory value is clinically relevant
• Use of any non-registered investigational drugs during 3 months before screening or previous participation in the study

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 20 Years to 39 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01922193
• Other Study ID Numbers: 000089
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ferring Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Ferring Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Development Support; Ferring Pharmaceuticals

• PRS Account: Ferring Pharmaceuticals
• Verification Date: June 2015