Female Infertility
Conditions
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.
Interventions
DRUGRecombinant Human Follicle Stimulating Hormone 900 IU (66.0 μg) / 1.5mL Solution for Injection in Prefilled Pen
fixed-dose of 225 IU/day, subcutaneous (SC), daily, for 5 days. further dosage will be adjusted till adequate follicular development.
Sponsors
Bharat Serums and Vaccines Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The assessor including the investigator, outcoume assessor (sonography, embyrologist) shall be blinded.
Intervention model description
This is a Randomized, Parallel-group, Multi-Center, Assessor-blind Phase 3 Study.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 39 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of oocytes retrieved | Oocyte pick up - up to ~ 34 to 36 hours after human chorionic gonadotropin (hCG) administration | Number of oocytes retrieved |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing Pregnancy rate | 11±1 weeks after ET | Ongoing pregnancy rate |
| Cycle cancellation rate | 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 | Cycle cancellation rate |
| Total Doseof r-hFSH | at end of stimulation up to 20 days | Total dose of r-hFSH (in IU) required for ovarian stimulation; |
| Number of Days of r-hFSH stimulation | at end of stimulation up to 20 days | Number of days of r-hFSH stimulation |
| Number of subject Change in Dosage | post Day 6 till end of stimulation up to 20 days | Proportion of subjects requiring change in dose |
| Hormonal Investigation | Day 6 | Estradiol, Luteinizing, Progesterone, and inhibin b levels |
| Follicle size on Day 6 | Day 6 | Number of follicles with size \<11mm, Number of follicles with size 11- 14 mm, Number of follicles with size15 mm, Number of follicles with size16 mm, Number of follicles with size17 mm and Number of follicles with size ≥18 mm |
| Follicle size at HCG administration | Day of hCG administration anytime upto 3 weeks | Number of follicles with size \<11mm, Number of follicles with size 11- 14 mm, Number of follicles with size15 mm, Number of follicles with size16 mm, Number of follicles with size17 mm and Number of follicles with size ≥18 mm mm) |
| Clinical pregnancy rate | 4 weeks after embryo transfer (ET) | Clinical pregnancy rate |
| Endometrium at HCG administration | day of hCG injection (anytime upto 3 weeks) | Endometrial thickness (mm) |
| Evaluation of immunogenicity (antibody) of r-hFSH | Baseline, 4 weeks and 12 weeks | Evaluation of immunogenicity of r-hFSH, comparison of antibody titre against r-hFSH in both groups |
| Number of Matured oocytes | Oocyte pick up ~ 34 to 36 hours after hCG administration | Proportion of matured oocytes |
| Number of good quality embryos | ET day (up to 8 weeks) | Number of good quality embryos |
| Number of Adverse events | 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 | Number of treatment-emergent adverse events (TEAE) reported |
| Specific adverse events | Day 1 of Stimulation till ~12 weeks after ET | The number of patients with ovarian hyperstimulation syndrome (OHSS) reported |
| Exploratory | End of stimulation up to 20 days | Ease of use of Pen - comparison of total score of Questionnaire to user of rhFSH pen |
| Endometrium thickness | day 6 | Endometrial thickness (mm) |
Countries
India
Outcome results
None listed