Investigation of a Long-Acting Follicle Stimulating Hormone in Infertile Women Undergoing Assisted Reproductive Technology (ART)

Phase 2

Completed

Conditions: Infertility

Interventions: Drug: AS900672-Enriched 50 microgram (mcg)
Drug: AS900672-Enriched 100 mcg
Drug: AS900672-Enriched 150 mcg
Drug: Follitropin alfa 150 international unit (IU)
Drug: Recombinant human chorionic gonadotropin (r-hCG)

Registration Number: NCT00505752

Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 520

Inclusion Criteria

Not provided

Exclusion Criteria

Subject who require a starting dose of FSH greater than (>) 150 international unit per day (IU/day), in the opinion of the Investigator
Screening ultrasound demonstrating more than 12 follicles less than (<) 11 mm mean diameter in either ovary
Two or more previous ART cycles (consecutive or not) with poor response to gonadotrophin, defined as less than or equal to (=<)3 oocytes retrieved
Three or more previous consecutive ART cycles without a biochemical or clinical pregnancy
Previous failure of fertilization with ICSI
A previous ART attempt in which there were no adequate or motile sperm before or after the processing of ejaculated sperm
Previous severe OHSS
History or presence of tumors of the hypothalamus or pituitary gland
History or presence of ovarian, uterine or mammary cancer
History or presence of ovarian enlargement or cyst of unknown etiology, or presence of ovarian cyst >25 mm on the day of randomization
Presence of endometriosis Grade III - IV
Presence of uni- or bilateral hydrosalpinx
Abnormal gynecological bleeding of undetermined origin
Contraindication to being pregnant and/or carrying a pregnancy to term
History of >= 3 clinical or preclinical (absence of gestational sac) miscarriages due to any cause
Extra-uterine pregnancy within the 3 months prior to randomization
Clinically significant concurrent disease that would have compromised subject safety or interfered with the study assessments
Known infection with human immunodeficiency virus (HIV), hepatitis B or C virus in the female or male partner
Known allergy or hypersensitivity to human gonadotrophin preparations or to compounds that are structurally similar to any of the other medications administered during the study
Any medical condition, which in the judgment of the Investigator may have interfere with the absorption, distribution, metabolism or excretion of r-hFSH
Any active substance abuse or history of drug, medication or alcohol abuse within 5 years before screening
ART cycle and/or ovarian stimulation within 30 days prior to informed consent
Entered previously into this study or simultaneous participation in another clinical trial
Subject is a smoker consuming more than 5 cigarettes per day
In the opinion of the Investigator, either assisted hatching or pre-implantation genetic diagnosis is indicated for the subject
Planning to undergo experimental procedures such as blastomere biopsy, or
Any known autoimmune disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AS900672-Enriched 50 mcg	AS900672-Enriched 50 microgram (mcg)	-
AS900672-Enriched 50 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 100 mcg	AS900672-Enriched 100 mcg	-
AS900672-Enriched 100 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 150 mcg	AS900672-Enriched 150 mcg	-
AS900672-Enriched 150 mcg	Recombinant human chorionic gonadotropin (r-hCG)	-
Follitropin alfa 150 IU	Recombinant human chorionic gonadotropin (r-hCG)	-
AS900672-Enriched 50 mcg	Follitropin alfa 150 international unit (IU)	-
AS900672-Enriched 100 mcg	Follitropin alfa 150 international unit (IU)	-
AS900672-Enriched 150 mcg	Follitropin alfa 150 international unit (IU)	-
Follitropin alfa 150 IU	Follitropin alfa 150 international unit (IU)	-

Primary Outcome Measures

Name	Time	Method
Number of Fertilized Oocytes (2 Pronuclei [PN])	Ovum pick-up (OPU) day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 21 days}])	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Pregnancy	Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])	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.