Recombinant Follicle-stimulating Hormone in Treatment for Infertility

A Randomized, Parallel-group, Multi-Center, Assessor-blind Phase 3 Study to Compare the Efficacy, Safety and Ease of Use of Two Follicle Stimulating Hormone -Human Recombinant (r-hFSH) 900 IU (66.0 μg) / 1.5mL Solution for Injection in Prefilled Pen (Foligraf®- Manufactured by BSV and Gonal-f® Manufactured by Merck Serono) in Subjects Undergoing Controlled Ovarian Stimulation for Assisted Reproductive Technology

This is a randomized multi-centre, assessor-blind, parallel-group study to be conducted in 250 women in the age group of 20 to 39 years (both inclusive), who are indicated to undergo COS as part of assisted reproductive technology (ART). The participant will receive r-hFSH, fixed-dose for 5 days, and day 6 onwards the dose may be adjusted for a single cycle of COS followed by ART procedures, and post-ART follow-up for ongoing pregnancy.

The primary and secondary outcomes will be captured on days as per protocol. Adverse events will be noted for safety evaluation.

Inclusion Criteria:

• Subject has indication ART using COS.

• Subject has regular menstrual cycle of 21-35 days.

• Subject has one of the following:

  1. FSH level <10 IU/L and Estradiol levl <80 pg/mL at day 2 or 3
  2. Anti-mullerian hormone (AMH) level between 1 to 3.5 ng/mL during the menstrual cycle

• Subject has an antral follicle count (AFC) of 10- 25, follicle ≤10 mm in diameter before ovarian stimulation

• Subject has a BMI ≥18 and <30 kg/m2

• Subject has results of clinical laboratory tests within normal reference range

• Subject and her partner are willing to provide written informed consent and comply

Exclusion Criteria Details Subject has history of >2 failed ART cycles

• Subject with history of any endocrine abnormality, with documented hormone levels outside the reference range, which are clinically relevant, at screening

• Subject with a history of ovarian hyper-response (i.e., previous COS cycle with >25 follicles of ≥11 mm in diameter on USG) or OHSS

• Subject with documented polycystic ovarian syndrome (PCOS) at the time of screening

• Subject with only one ovary or ovarian abnormality (including endometrioma >10 mm; visible on USG), at screening

• Subject with documented severe endometriosis (American Society of Reproductive Medicine stage 3 or stage 4) or hydrosalpinx, at screening

• Subject with submucosal fibroids ≥5 cm or any other clinically relevant pathology, which could impair embryo implantation or pregnancy continuation, at screening

• Subject with a history of extrauterine pregnancy within 3 months of screening

• Subject with history of poor response to gonadotropin treatment (retrieval of <4 oocytes) in the previous ART cycle

• Subject with history of ≥3 miscarriages, at any time prior to screening

• Subject who has tested positive for Human Immunodeficiency Virus, Hepatitis B or Hepatitis C at screening

• Subject known to be allergic, hypersensitive, or intolerant to any of the preparations of r hFSH or its excipients, that will be used in the study

• Subject with contraindications to the use of gonadotropins (e.g., tumours, undiagnosed vaginal bleeding, or ovarian cysts) or gonadotropin-releasing hormone (GnRH) antagonists

• Subject with a history of epilepsy, thrombophilia, cardiovascular, gastrointestinal, hepatic, renal, pulmonary, auto-immune disease, or any active infection, requiring treatment which at the investigator's discretion might interfere with the study

• Subject with history of malignancy

• Subject who smokes or has stopped smoking within the last 3 months prior to screening

• Subject with history of alcohol or drug abuse within 12 months prior to screening

• Subject who has received any treatment listed below within 5 half-lives prior to screening:

  1. Any agent(s) known to affect ovulation (e.g., neuroleptics);
  2. Drugs known or suspected to be teratogenic in nature.