Clinical trial NCT01144416: Efficacy and Safety Study of a Single Injection of SCH 900962 Versus Daily recFSH Injections in Women Undergoing Controlled Ovarian Stimulation (Study P06029)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: Reproductive Techniques, Assisted
Follicle Stimulating Hormone, Human
Fertilization In Vitro
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2010-06-15
Enrollment: 1424
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants With a Vital Pregnancy
timeFrame: 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 outcomes:
measure: Number of Oocytes Retrieved Per Attempt
timeFrame: Maximally 21 days after the start of study treatment.
measure: Live Birth Rate
timeFrame: Approximately nine months after embryo transfer
measure: Number of Participants With Moderate or Severe Ovarian Hyperstimulation Syndrome (OHSS)
timeFrame: Up to approximately 1 month after oocyte pick-up
measure: Number of Participants Who Cancelled the Cycle Due to a (Serious) Adverse Event
timeFrame: Up to time of embryo transfer (maximum of 24 days after start of study drug)
Other outcomes:
Locations:
Study officials:
References:
citation: Boostanfar R, Shapiro B, Levy M, Rosenwaks Z, Witjes H, Stegmann BJ, Elbers J, Gordon K, Mannaerts B; Pursue investigators. Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization. Fertil Steril. 2015 Jul;104(1):94-103.e1. doi: 10.1016/j.fertnstert.2015.04.018. Epub 2015 May 21.
citation: Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016 Nov;31(11):2554-2560. doi: 10.1093/humrep/dew213. Epub 2016 Sep 12.
citation: Zandvliet AS, Prohn M, de Greef R, van Aarle F, McCrary Sisk C, Stegmann BJ. Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation. Br J Clin Pharmacol. 2016 Jul;82(1):74-82. doi: 10.1111/bcp.12939. Epub 2016 May 31.
citation: Oehninger S, Nelson SM, Verweij P, Stegmann BJ. Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation in IVF/ICSI cycles. Reprod Biol Endocrinol. 2015 Oct 31;13:117. doi: 10.1186/s12958-015-0113-1.