Efficacy and Safety Study of a Single Injection of SCH 900962 Versus Daily recFSH Injections in Women Undergoing Controlled Ovarian Stimulation (Study P06029)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to show that a single injection of SCH 900962/MK-8962 is non-inferior to daily injections of recombinant follicle-stimulating hormone (recFSH) during the first week of ovarian stimulation in terms of the number of vital pregnancies (ie, presence of at least one fetus with heart activity as assessed by ultrasound at least 35 days after embryo transfer) in women aged 35 to 42 years undergoing controlled ovarian stimulation (COS) prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Official Title
-----------------
A Phase 3, Randomized, Double-blind, Active-controlled, Non-inferiority Trial to Investigate the Efficacy and Safety of a Single Injection of SCH 900962 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation (COS) Using Daily Recombinant FSH (recFSH) as a Reference in Women Aged 35 to 42 Years (Phase 3; Protocol No. P06029)

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Biological: SCH 900962 / Corifollitropin alfa / Org 36286
* Biological: RecFSH / follitropin beta
* Drug: Placebo for SCH 900962
* Drug: Placebo for recFSH


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent for trial P06029 as well as for the Frozen-Thawed Embryo Transfer (FTET) follow-up trial P06031, and for the pharmacogenetic analysis (if applicable). Female and >=35 to <=42 years of age with indication for COS and IVF/ICSI. Body weight ≥50.0 kg, body mass index (BMI) >=18.0 to <=32.0 kg/m2. Regular spontaneous menstrual cycle with variation not outside the 24-35 days. Ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed). Results of clinical laboratory tests, cervical smear, physical examination within normal limits or clinically acceptable to the investigator. Adhere to trial schedule. Exclusion Criteria: A recent history of/or any current endocrine abnormality. A history of ovarian hyper-response or ovarian hyperstimulation syndrome (OHSS). A history of/or current polycystic ovary syndrome. More than 20 basal antral follicles <11 mm (both ovaries combined) in the early follicular phase. Less than 2 ovaries or any other ovarian abnormality. Unilateral or bilateral hydrosalpinx. Intrauterine fibroids ≥5 cm or any clinically relevant pathology, which could impair embryo implantation or pregnancy continuation. More than three unsuccessful COS cycles for IVF/ICSI since the last established ongoing pregnancy (if applicable). A history of non- or low ovarian response to FSH/human menopausal gonadotropin (hMG) treatment. A history of recurrent miscarriage. FSH >15.0 IU/L or luteinizing hormone (LH) >12.0 IU/L during the early follicular phase. Positive for human immunodeficiency virus (HIV) or Hepatitis B. Contraindications for the use of gonadotropins or gonadotropin releasing hormone (GnRH) antagonists. A recent history of/or current epilepsy, thrombophilia, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary or auto-immune disease requiring regular treatment. Smoking or recently stopped smoking (ie, within the last 3 months prior to signing informed consent). A recent history or presence of alcohol or drug abuse. The participant or the sperm donor has known gene defects, genetic abnormalities, or abnormal karyotyping, relevant for the current indication or for the health of the offspring. Prior or concomitant medications disallowed by protocol.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 42 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single injection of 150 µg SCH 900962 (MK-8962)<br>Participants received a single injection of 150 ug SCH 900962 (MK-8962) on Stimulation Day 1 and 7 injections with placebo-recFSH from Stimulation Days 1-7 | Biological: SCH 900962 / Corifollitropin alfa / Org 36286<br>* SCH 900962 will be provided as ready-for-use prefilled syringes containing 150 μg corifollitropin alfa per 0.5 mL. On day 2 or 3 of the menstrual cycle, a single dose of 150 μg corifollitropin alfa will be administered by subcutaneous injection in the abdominal wall in the morning.<br>* Other names: MK-8962;Drug: Placebo for recFSH<br>* Supplied as identical ready-for-use solution, but without the active ingredient, in cartridges for subcutaneous injection with the Follistim Pen. Starting on day 2 or 3 of the menstrual cycle (=Stimulation Day 1), administration of placebo-recFSH will be done by daily injections in the abdominal wall in the morning for a period of 7 days.<br>|
| Active Comparator: Daily 300 IU recFSH<br>Participants received a single injection of placebo SCH 900962 (MK-8962) on Stimulation Day 1 and 7 injections of recFSH from Stimulation Days 1-7 | Biological: RecFSH / follitropin beta<br>* RecFSH will be provided as a ready-for-use solution in 900 IU cartridges for subcutaneous injection with the Follistim Pen. Starting on day 2 or 3 of the menstrual cycle (=Stimulation Day 1), administration of recFSH will be done in the morning by daily injections in the abdominal wall. A starting dose of 300 IU will be administered and fixed for at least 7 days.<br>* Other names: Follistim® AQ Cartridge;Drug: Placebo for SCH 900962<br>* Supplied as a pre-filled syringe containing an identical solution when compared to SCH 900962, however without the active ingredient corifollitropin alfa. On Day 2 or 3 of the menstrual cycle (=Stimulation Day 1), a single dose of placebo SCH 900962 is to be administered in the morning by subcutaneous injection in the abdominal wall.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Vital Pregnancy | Vital pregnancy was defined as the presence of at least 1 fetus with heart activity at least 35 days (≥5 weeks) after embryo transfer in the controlled ovarian stimulation (COS) treatment cycle | Vital pregnancy will be assessed by ultrasound at least 35 days after embryo transfer (with a timeframe of 35-42 days). Time from start of study treatment to embryo transfer is maximally 24 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Oocytes Retrieved Per Attempt | The number of cumulus oocyte-complexes retrieved was summarized per treatment group and per attempt (= per started COS cycle). | Maximally 21 days after the start of study treatment. | 
| Live Birth Rate | The live-birth rate is the percentage of participants with at least 1 live born infant after an ongoing pregnancy in the controlled ovarian stimulation (COS)treatment cycle relative to the number of participants treated. | Approximately nine months after embryo transfer | 
| Number of Participants With Moderate or Severe Ovarian Hyperstimulation Syndrome (OHSS) | Grade II (moderate OHSS) is characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea. Grade III (severe OHSS) is characterized by enlarged cystic ovaries (ovary size >10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm, may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause hemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena. | Up to approximately 1 month after oocyte pick-up | 
| Number of Participants Who Cancelled the Cycle Due to a (Serious) Adverse Event | The number of participants who started stimulation but did not undergo embryo transfer due to (S)AEs will be compared between the treatment groups. | Up to time of embryo transfer (maximum of 24 days after start of study drug) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Reproductive Techniques, Assisted, Follicle Stimulating Hormone, Human, Fertilization In Vitro