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

Infertility Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01922193
• Other study ID #: 000089
• Status: Completed
• Phase: Phase 3
• First received: July 24, 2013
• Last updated: June 15, 2015
• Start date: October 2013
• Est. completion date: April 2015

Study information

• Verified date: June 2015
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 263
• Est. completion date: April 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 39 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Highly Purified Urofollitropin
for injection
• Recombinant Human Follitropin Alfa
for injection

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Sun Yat-sen Memorial Hospital Sun Yat-sen University	Guangzhou	Guangdong
China	The third Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu
China	ShengJing Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical College of HUST Tongji Medical College Huazhong University of Science & Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of retrieved oocytes per cycle		About 36 hours post hCG (human chorionic gonadotrophin)	No
Secondary	The follicles development		At day 5 of FSH preparation stimulation and the day of hCG administration	No
Secondary	The fertilization rate		20h (± 1h) after insemination	No
Secondary	Implantation rate		5-6 weeks post embryo transfer	No
Secondary	Cycle cancellation rate		36 hours post hCG	No
Secondary	The positive serum ß-hCG/hCG rate		13-15 days after embryo transfer	No
Secondary	The clinical pregnancy rate	Regardless of fetal heart beat	5-6 weeks after embryo transfer	No
Secondary	The clinical pregnancy rate	With fetal heart beat	5-6 weeks after embryo transfer	No
Secondary	The ongoing pregnancy rate		10-11 weeks after embryo transfer	No
Secondary	Total gonadotropin dose administered and the duration of gonadotropin treatment		Up to day 16 (in the stimulation period)	No
Secondary	Serum E2 (Estradiol) concentrations		On the day of hCG administration	No
Secondary	Frequency and severity of adverse events		Expected maximum of 7 months	Yes
Secondary	Frequency and severity of injection site reactions	Injection site reactions (in terms of "redness", "pain", "itching", "swelling" and "bruising")	Day 1 up to day 16 of the controlled ovarian stimulation period	Yes