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 and Co397 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

397

Conditions

Infertility

Interventions

corifollitropin alfa (Org 36286)DRUG

100 µg corifollitropin alfa subcutaneous (SC) injection

recFSH (follitropin beta)DRUG

150 IU recFSH SC injection

gonadatropin releasing hormone (GnRH) antagonist (ganirelix)DRUG

GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 36 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of Cumulus-oocyte-complexes Retrieved, Per Attempt

The primary efficacy parameter was defined as the number of cumulus-oocyte-complexes retrieved from participants in a controlled ovarian stimulation (COS) cycle for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). For participants who did not have cumulus-oocyte-complex retrieval, the number retrieved was set to zero.

Time frame: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)

Secondary Outcomes

Total Dose of recFSH Administered

Total dose of recFSH (IU) administered was defined as the total amount of recFSH needed by participants to reach the criterion for administration of hCG (at least 3 follicles \>=17mm).

Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)

Total Dose of recFSH Administered From Day 8 Onwards

Total dose of recFSH (IU) needed from Stimulation Day 8 onwards to reach the criterion for administration of hCG (at least 3 follicles \>=17mm).

Time frame: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)

Number of Days Treated With recFSH

Numbers of days treated with recFSH was defined as the total number of days participants received recFSH (excluding coasting days) until they reached the criterion for administration of hCG (at least 3 follicles \>=17mm).

Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)

Total Duration of Stimulation (Days)

Total duration of stimulation was defined as the number of days from first drug administration up to and including the Day of hCG administration.

Time frame: One COS cycle (up to a maximum total duration of 19 stimulation days)

Data from ClinicalTrials.gov

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hCG 5,000 IU or 10,000 IU administered SC

progesteroneBIOLOGICAL

Progesterone was started on the day of oocyte pick-up (OPU) and continued for at least 6 weeks or up to menses. Participants received at least 600 mg/day vaginally or 50 mg/day IM.

placebo-recFSH (follitropin alfa)DRUG

Placebo-recFSH administered at the equivalent volume of 150 IU/day.

placebo-corifollitropin alfaDRUG

Single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle.

open-label recFSHBIOLOGICAL

Open-label recFSH administered up to a maximum dose of 200 IU/day.

Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection)

Blood samples for assessment of serum FSH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET.