To Investigate Efficacy and Safety of a Single Injection of Org 36286 for Ovarian Stimulation Using Daily Recombinant FSH as Reference (Ensure)(P05690/MK-8962-001)

Organon

Status and phase: Completed; Phase 3

Conditions: Infertility

Treatments: Drug: human chorion gonadatropin (hCG); Biological: progesterone; Drug: placebo-recFSH (follitropin alfa); Drug: placebo-corifollitropin alfa; Drug: recFSH (follitropin beta); Drug: corifollitropin alfa (Org 36286); Drug: gonadatropin releasing hormone (GnRH) antagonist (ganirelix); Biological: open-label recFSH

Study type: Interventional

Funder types: Industry

Identifiers

NCT00702845

107012 (Other Identifier)

P05690

2006-003811-36 (EudraCT Number)

Details and patient eligibility

About

Clinical trial objectives are to investigate the efficacy and safety of a single injection of 100 μg Org 36286 in women weighing 60 kg or less to induce multifollicular development for controlled ovarian stimulation (COS), using daily recFSH as a reference.

Full description

This is a randomized, double-blind, active-controlled, equivalence clinical trial investigating the efficacy and safety of a new treatment regimen with Org 36286, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in COS for Assisted Reproductive Technology (ART). For this regimen, patients receive a single injection of Org 36286 and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group patients receive daily injections of recFSH up to the day of triggering final oocyte maturation. Equivalence between the two treatment groups in the number of oocytes retrieved is the primary objective of this trial.

Enrollment: 397 patients

Sex: Female

Ages: 18 to 36 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females of couples with an indication for COS and IVF or ICSI;
• >=18 and <= 36 years of age at the time of signing informed consent;
• Body weight <= 60 kg and BMI >= 18 and <= 32 kg/m^2;
• Normal menstrual cycle length: 24-35 days;
• Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed);
• Willing and able to sign informed consent.

Exclusion criteria

• History of/or any current (treated) endocrine abnormality;
• History of ovarian hyper-response or ovarian hyperstimulation syndrome

(OHSS);

• History of/or current polycystic ovary syndrome (PCOS);
• More than 20 basal antral follicles <11 mm (both ovaries combined) as measured on USS in the early follicular phase (menstrual cycle day 2-5);
• Less than 2 ovaries or any other ovarian abnormality (including endometrioma > 10 mm; visible on USS);
• Presence of unilateral or bilateral hydrosalphinx (visible on USS);
• Presence of any clinically relevant pathology affecting the uterine cavity or fibroids >= 5 cm;
• More than three unsuccessful IVF cycles since the last established ongoing

pregnancy (if applicable);

• History of non- or low ovarian response to FSH/hMG treatment;
• History of recurrent miscarriage (3 or more, even when unexplained);
• FSH > 12 IU/L or LH > 12 IU/L as measured by the local laboratory (sample taken during the early follicular phase: menstrual cycle day 2-5);
• Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase;
• Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts);
• Recent history of/or current epilepsy, HIV infection, diabetes, cardiovascular,

gastro-intestinal, hepatic, renal or pulmonary disease;

• Abnormal karyotyping of the patient or her partner (if karyotyping is performed);
• Smoking more than 5 cigarettes per day;
• History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
• Previous use of Org 36286;
• Use of hormonal preparations within 1 month prior to randomization;
• Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol;
• Administration of investigational drugs within three months prior to signing informed consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

397 participants in 2 patient groups

corifollitropin alfa 100 µg

Experimental group

Description:

Participants received a single subcutaneous (SC) injection of corifollitropin alfa 100 μg (Org 36286) on Day 2 or 3 of the menstrual cycle and daily placebo-recombinant Follicle Stimulating Hormone (recFSH) injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants also received open-label recFSH (up to 200 IU/day) from Stimulation Day 8 onwards, up to and including Day of Human Chorion Gonadotropin (hCG) administration. Participants also received Gonadotropin Releasing Hormone (GnRH) antagonist ganirelix (0.25 mg) once daily SC starting on Stimulation Day 5 up to and including the Day of hCG (10,000 or 5,000 IU/USP). Participants also received progesterone (at least 600 mg/day vaginally or 50 mg/day by intramuscular \[IM\] injection), starting on day of oocyte pick-up (OPU) and continuing for at least 6 weeks or up to menses.

Treatment:

Biological: open-label recFSH

Drug: gonadatropin releasing hormone (GnRH) antagonist (ganirelix)

Drug: corifollitropin alfa (Org 36286)

Drug: placebo-recFSH (follitropin alfa)

Biological: progesterone

Drug: human chorion gonadatropin (hCG)

recFSH 150 IU

Active Comparator group

Description:

Participants in the reference group received a single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle and daily SC recFSH 150 IU injections (7 total) from Stimulation Day 1 up to and including Stimulation Day 7. Participants also received open-label recFSH (up to 200 IU/day) from Stimulation Day 8 onwards, up to and including the day of hCG (10,000 or 5,000 IU/USP) administration. Participants also received the GnRH antagonist ganirelix (0.25 mg) once daily SC starting on Stimulation Day 5 up to and including the Day of hCG. Participants also received progesterone (at least 600 mg/day vaginally or 50 mg/day IM), starting on the day of OPU and continuing for at least 6 weeks or up to menses.

Treatment:

Biological: open-label recFSH

Drug: gonadatropin releasing hormone (GnRH) antagonist (ganirelix)

Drug: placebo-corifollitropin alfa

Drug: recFSH (follitropin beta)

Biological: progesterone

Drug: human chorion gonadatropin (hCG)