Clinical trial NCT05266924: Recombinant Follicle-stimulating Hormone in Treatment for Infertility
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Female Infertility
Lead sponsor: Bharat Serums and Vaccines Limited
Sponsor class: INDUSTRY
First posted: 2022-03-04
Enrollment: 250
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Randomized, Parallel-group, Multi-Center, Assessor-blind Phase 3 Study.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of oocytes retrieved
timeFrame: Oocyte pick up - up to ~ 34 to 36 hours after human chorionic gonadotropin (hCG) administration
Secondary outcomes:
measure: Clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer (ET)
measure: Ongoing Pregnancy rate
timeFrame: 11±1 weeks after ET
measure: Cycle cancellation rate
timeFrame: at Stimulation phase up to 20 days, oocyte pick up up to ~ 34 to 36 hours after hCG administration, ET anytime up to 8 weeks
measure: Total Doseof r-hFSH
timeFrame: at end of stimulation up to 20 days
measure: Number of Days of r-hFSH stimulation
timeFrame: at end of stimulation up to 20 days
measure: Number of subject Change in Dosage
timeFrame: post Day 6 till end of stimulation up to 20 days
measure: Hormonal Investigation
timeFrame: Day 6
measure: Follicle size on Day 6
timeFrame: Day 6
measure: Follicle size at HCG administration
timeFrame: Day of hCG administration anytime upto 3 weeks
measure: Endometrium thickness
timeFrame: day 6
measure: Endometrium at HCG administration
timeFrame: day of hCG injection (anytime upto 3 weeks)
measure: Number of Matured oocytes
timeFrame: Oocyte pick up ~ 34 to 36 hours after hCG administration
measure: Number of good quality embryos
timeFrame: ET day (up to 8 weeks)
measure: Number of Adverse events
timeFrame: Baseline, 1st day of stimulation, day 6 , end of stimulation up to 20 days, hCG administration, oocyte pick up ~ 34 to 36 hours after hCG administration, ET up to 8 weeks, clinical pregnancy (after 4 weeks of ET), ~12 weeks after ET
measure: Specific adverse events
timeFrame: Day 1 of Stimulation till ~12 weeks after ET
measure: Exploratory
timeFrame: End of stimulation up to 20 days
measure: Evaluation of immunogenicity (antibody) of r-hFSH
timeFrame: Baseline, 4 weeks and 12 weeks
Other outcomes:
Locations:
city: Varanasi
country: India
facility: Om Research Center Om Surgical Center and Maternity Home
state: Uttar Pradesh
Study officials:
References: