This is a Phase 2, interventional, prospective, multi-center, randomized, assessor-blind, active-comparator, dose-finding study to evaluate a new investigational long-acting follicle stimulating hormone (FSH) in infertile women who are undergoing an assisted reproductive technology (ART) procedure (In vitro fertilization/Intra cytoplasmic sperm injection \[IVF/ICSI\]). This study will compare 3 doses of the investigational drug versus a currently marketed drug follitropin alfa (Gonal-f® revised formulation female \[RFF\] Pen) in regards to the number of fertilized oocytes.
Infertile women who are candidates for ART will be prospectively screened for enrollment at 24 clinical trial sites in the United States and Argentina. Enrolled subjects will start treatment using oral contraceptives (OCP) and will then receive a Gonadotropin releasing hormone (GnRH)-agonist (leuprolide acetate) for pituitary desensitization. Once down-regulation is achieved, the subjects will be randomized in a 1:1:1:1 ratio to begin ovarian stimulation with one of 3 doses of AS900672-Enriched or with follitropin alfa (Gonal-f®) daily injections. Subjects will be recruited to the four study arms in parallel. Beginning on S1, the subjects will receive either a single injection of AS900672-Enriched or start daily injections of follitropin alfa. The subjects' response to treatment will be monitored by ovarian ultrasound and E2 levels. On S6, subjects randomized to AS900672-Enriched may begin receiving supplemental follitropin alfa 150 IU, according to the each subject's ovarian response, and subjects randomized to follitropin alfa 150 IU daily injections will continue treatment at the same dose. Recombinant human chorionic gonadotropin (r-hCG, Ovidrel®) will be administered to subjects meeting response criteria and who are not at risk for ovarian hyperstimulation syndrome (OHSS). Oocyte retrieval will occur within 34-38 hours after r-hCG administration and subjects will begin luteal phase support using vaginal progesterone (Crinone® 8 percent or Prochieve® 8 percent) the following day. Fertilization will be done by conventional IVF or ICSI. Embryo transfer will occur in accordance with the specific requirements of each subject and the clinical trial site's standard practice, with the exception that a maximum of two embryos at the cleavage or blastocyst stage may be transferred. Subjects who undergo embryo transfer will be assessed for pregnancy and a follow-up visit will be performed 15-20 days post r-hCG administration. Subjects with a positive pregnancy test will undergo a confirmatory ultrasound evaluation at Day 35 - 42 post r-hCG. Additionally, all subjects recruited at certain trial centers will participate in a pharmacokinetic (PK) sub-study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
520
Single injection of AS900672-Enriched (hyperglycosylated recombinant human follicle stimulating hormone \[r-hFSH\]), 50 mcg will be administered subcutaneously on Stimulation Day 1 (S1). Duration of treatment cycle will be up to adequate follicular response or maximum of 21 days.
Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 100 mcg will be administered subcutaneously on S1. Duration of treatment cycle will up to adequate follicular response or maximum of 21 days.
Single injection of AS900672-Enriched (hyperglycosylated r-hFSH), 150 mcg will be administered subcutaneously on S1. Duration of treatment cycle will up to adequate follicular response or maximum of 21 days.
Follitropin alfa (Gonal-f®) 150 IU will be administered subcutaneously once daily from S1 up to Stimulation Day 21 (S21) based upon ovarian response, until recombinant human chorionic gonadotropin (r-hCG) administration day. Subjects who will be receiving AS900672-Enriched 50, 100 and 150 mcg will also receive daily dose of follitropin alfa 150 IU subcutaneously from Stimulation Day 6 (S6) up to S21. Duration of treatment cycle will be up to adequate follicular response or maximum of 21 days.
Recombinant human chorionic gonadotropin (r-hCG) will be administered as a single dose of 250 mcg subcutaneously, when follicular response is adequate (that is, at least 1 follicle with a diameter of greater than or equal to \[\>=\] 18 millimeter \[mm\], two or more additional follicles with a diameter of \>= 16 mm, and Estradiol \[E2\] levels will approximately 150 picogram per milliliter \[pg/mL\] per mature follicle).
Local US Medical Information Office
Rockland, Massachusetts, United States
Number of Fertilized Oocytes (2 Pronuclei [PN])
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN.
Time frame: Ovum pick-up (OPU) day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
Percentage of Participants With Clinical Pregnancy
Clinical pregnancy was defined as the presence of one or more fetal sacs with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination.
Time frame: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
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