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)

NCT ID: NCT00702845

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 397 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-28
• Study Completion Date: 2007-11-15

Brief Summary

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.

Detailed 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.

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

corifollitropin alfa 100 µg

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.

Group Type: EXPERIMENTAL

corifollitropin alfa (Org 36286)

Intervention Type: DRUG

100 µg corifollitropin alfa subcutaneous (SC) injection

gonadatropin releasing hormone (GnRH) antagonist (ganirelix)

Intervention Type: DRUG

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

human chorion gonadatropin (hCG)

Intervention Type: DRUG

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

progesterone

Intervention Type: BIOLOGICAL

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)

Intervention Type: DRUG

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

open-label recFSH

Intervention Type: BIOLOGICAL

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

recFSH 150 IU

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.

Group Type: ACTIVE_COMPARATOR

recFSH (follitropin beta)

Intervention Type: DRUG

150 IU recFSH SC injection

gonadatropin releasing hormone (GnRH) antagonist (ganirelix)

Intervention Type: DRUG

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

human chorion gonadatropin (hCG)

Intervention Type: DRUG

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

progesterone

Intervention Type: BIOLOGICAL

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-corifollitropin alfa

Intervention Type: DRUG

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

open-label recFSH

Intervention Type: BIOLOGICAL

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

Interventions

corifollitropin alfa (Org 36286)

100 µg corifollitropin alfa subcutaneous (SC) injection

Intervention Type: DRUG

recFSH (follitropin beta)

150 IU recFSH SC injection

Intervention Type: DRUG

gonadatropin releasing hormone (GnRH) antagonist (ganirelix)

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

Intervention Type: DRUG

human chorion gonadatropin (hCG)

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

Intervention Type: DRUG

progesterone

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.

Intervention Type: BIOLOGICAL

placebo-recFSH (follitropin alfa)

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

Intervention Type: DRUG

placebo-corifollitropin alfa

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

Intervention Type: DRUG

open-label recFSH

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Org 36286; recFSH (Puregon/Follistim AQ Cartridge)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 36 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Organon and Co

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Corifollitropin alfa Ensure Study Group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online. 2010 Jul;21(1):66-76. doi: 10.1016/j.rbmo.2010.03.019. Epub 2010 Mar 28.

Reference Type: RESULT

PMID: 20483664 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26991902 (View on PubMed)

Griesinger G, Verweij PJ, Gates D, Devroey P, Gordon K, Stegmann BJ, Tarlatzis BC. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol. PLoS One. 2016 Mar 7;11(3):e0149615. doi: 10.1371/journal.pone.0149615. eCollection 2016.

Reference Type: DERIVED

PMID: 26950065 (View on PubMed)

Other Identifiers

2006-003811-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

107012

Identifier Type: OTHER

Identifier Source: secondary_id

P05690

Identifier Type: -

Identifier Source: org_study_id