A Study to Investigate the Efficacy and Safety of a Single Injection of Corifollitropin Alfa (Organon 36286) for Ovarian Stimulation Using Daily Recombinant Follicle Stimulating Hormone (FSH) as Reference (P05787)

In Vitro Fertilization Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Active-Controlled, Non-Inferiority Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation Using Daily Recombinant FSH as Reference

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00696800
• Other study ID #: P05787
• Secondary ID: 2004-004771-1138
• Status: Completed
• Phase: Phase 3
• Start date: June 27, 2006
• Est. completion date: January 15, 2008

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the efficacy and safety of a single injection of 150 μg Corifollitropin Alfa (Organon 36286) to induce multifollicular development for controlled ovarian stimulation using daily recombinant FSH (recFSH) as a reference. The primary hypothesis is that a single injection of Corifollitropin Alfa is non-inferior to daily treatment with recFSH in initiating multifollicular growth.

Description:

This is a randomized, double-blind, active-controlled, non-inferiority clinical trial investigating the efficacy and safety of a new treatment regimen with Corifollitropin Alfa, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in controlled ovarian stimulation for Assisted Reproductive Technology (ART). For this regimen, participants receive a single injection of Corifollitropin Alfa and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group participants receive daily injections of recFSH up to the day of triggering final oocyte maturation. Non-inferiority in ongoing pregnancy rates (assessed at least 10 weeks after embryo transfer) will be the primary endpoint for this trial. The number of oocytes retrieved will be analyzed as co-primary endpoint.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1509
• Est. completion date: January 15, 2008
• Est. primary completion date: November 19, 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 36 Years

Eligibility

Inclusion Criteria:

• Females of couples with an indication for Controlled Ovarian Stimulation (COS) and in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI);

• >=18 and <=36 years of age at the time of signing informed consent;

• Body weight > 60 and <=90 kg and body mass index (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 ultrasound scan (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/ human menopausal gonadotropin (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, human immunodeficiency virus (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.

Related Conditions & MeSH terms

• In Vitro Fertilization

Intervention

Drug:
• Corifollitropin alfa
On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection of 150 µg (0.5 mL) Corifollitropin Alfa was administered in the abdominal wall.

Biological:
• RecFSH / Follitropin beta (Days 1 to 7)
Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.

Drug:
• Placebo Corifollitropin alfa
Pre-filled syringe containing an identical solution when compared to Corifollitropin Alfa. On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection was administered in the abdominal wall.
• Placebo RecFSH / follitropin beta
Identical ready-for-use solution, but without the active ingedient, supplied in cartridges for SC injection with the Follistim Pen. Daily SC injections were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.

Biological:
• RecFSH / Follitropin beta (Days 8 to hCG)
From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG.

Drug:
• Ganirelix
On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG

Biological:
• hCG
When 3 follicles >= 17 mm were observed by USS, a single dose of 10,000 IU/USP hCG was administered; or, for those at risk for Ovarian Hyperstimulation Syndrome (OHSS), a lower dose of 5,000 IU/USP
• Progesterone
On the day of OPU, luteal phase support was started by administering micronized progesterone of at least 600 mg/day vaginally, or at least 50 mg/day intramuscular (IM), which continued for at least 6 weeks, or up to menses.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate)	An ongoing pregnancy is a fetus with heart activity at least 10 weeks after embryo transfer as assessed by Ultrasound Scan (USS) or Doppler or is confirmed by live birth. The ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy after embryo transfer, divided by the total number of participants who started treatment. Calculations were made per attempt, meaning that participants who did not have embryo transfers were considered not pregnant.	Assessed at least 10 weeks after embryo transfer (up to 1 year)
Primary	Mean Number of Oocytes Retrieved	Up to 36 hours after receiving hCG, cumulus-oocyte-complexes were retrieved. Mean numbers retrieved were calculated per attempt, meaning that if a participant did not reach this stage in In Vitro Fertilization (IVF) treatment, zero values were imputed.	Up to 36 hours after administration of hCG (up to 1 year)
Secondary	Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 1	The amount of recFSH administered for a participant to reach 3 follicles >= 17 mm, starting from treatment Day 1 onwards.	From Day 1 to day of hCG treatment (up to 1 year)
Secondary	Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 8	The amount of recFSH administered for a participant to reach 3 follicles >= 17 mm, starting from treatment Day 8 onwards.	From Day 8 to Day of hCG treatment (up to 1 year)
Secondary	Serum FSH Levels During Stimulation	Mean serum FSH are presented over one Controlled Ovarian Stimulation (COS) cycle: from Day 1 (Pre-dose) up to the day of hCG treatment.	Up to day of hCG treatment (up to 1 year)
Secondary	Serum Luteinizing Hormone (LH) Levels During Stimulation	Mean serum LH levels are presented over one COS cycle: from Day 1 (Pre-dose) up to the day of hCG treatment.	Up to day of hCG treatment (up to 1 year)
Secondary	Serum Estradiol (E2) Levels During Stimulation	Mean serum E2 levels are presented over one COS cycle: from Day 1 (Pre-dose) up to the day of hCG treatment.	Up to day of hCG treatment (up to 1 year)
Secondary	Serum Progesterone (P) Levels During Stimulation	Mean serum P levels are presented over one COS cycle: from Day 1 (Pre-dose) up to day of hCG treatment	Up to day of hCG treatment (up to 1 year)
Secondary	Serum Inhibin-B Levels During Stimulation	Mean serum Inhibin-B levels are presented over one COS cycle: from Day 1 (Pre-dose) up to day of hCG treatment	Up to day of hCG treatment (up to 1 year)
Secondary	Number of Follicles Categorized by Size on Stimulation Day 1	Ovaries were assessed during stimulation by ultrasonographic investigation (USS), and the mean number of follicles are categorized by their size.	On Day 1 of treatment (up to 1 year)
Secondary	Number of Follicles Categorized by Size on Stimulation Day 5	Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size.	On Day 5 of treatment (up to 1 year)
Secondary	Number of Follicles Categorized by Size on Stimulation Day 8	Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size.	On Day 8 of treatment (up to 1 year)
Secondary	Number of Follicles Categorized by Size on the Day of hCG	Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size.	Day of HCG treatment (up to 1 year)
Secondary	Number of Cumulus-oocyte-complexes	Prior to IVF the mean number of cumulus-oocyte-complexes used for IVF was assessed	Up to 36 hours after administration of hCG (up to 1 year)
Secondary	Number of Oocytes Assessed Prior to Intracytoplasmic Sperm Injection (ICSI)	The number of oocytes used for ICSI was assessed, and categorized based on their quality	Up to 36 hours after administration of hCG (up to 1 year)
Secondary	Percentage of Fertilized Oocytes (Fertilization Rate)	The fertilization rate is 100 times the number of fertilized 2 pro-nuclei (2PN) oocytes obtained, divided by the number of oocytes fertilized by IVF or ICSI	Up to 18 hours after start of fertilization (up to 1 year)
Secondary	Number of Embryos Obtained on Day 3 Categorized by Quality	Embryos obtained on Day 3 were categorized by their qualiity as follows: Grade 1: excellent: No fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 2: good: < 20% fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 3: fair: 20-50% fragmentation and/or less than 6 cells and/or multinucleation (if observed). Other Grade: Embryos that do not qualify as Grades 1, 2 or 3. Grades 1 and 2 are considered good quality.	Post fertilization Day 3 (up to 1 year)
Secondary	Number of Embryos Transferred on Day 3	After fertilization, the mean number of embryos transferred on Day 3 were assessed. Total and good quality embryos are presented, with good quality embryos, Grades 1 and 2, defined as the following: Grade 1: excellent: No fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 2: good: < 20% fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account.	Post fertilization Day 3 (up to 1 year)
Secondary	Percentage of Gestational Sacs (Implantation Rate)	The implantation rate is 100 times the number of gestational sacs assessed by USS after embryo transfer, divided by the number of embryos transferred.	Up to 6 weeks after embryo transfer (up to 1 year)
Secondary	Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Clinical Pregnancy	The miscarriage rate is 100 times the number of miscarriages, divided by the number of clinical pregnancies assessed by USS. A clinical pregnancy is the presence of at least one gestational sac or confirmed by live birth.	Up to day of miscarriage (up to 1 year)
Secondary	Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Vital Pregnancy	The miscarriage rate is 100 times the number of miscarriages, divided by the number of vital pregnancies assessed by USS. A vital pregnancy is the presence of at least one fetus with heart activity.	Up to day of miscarriage (up to 1 year)
Secondary	Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Attempt	Biochemical pregnancy was assessed by measuring serum or urinary hCG. Per attempt means that if a participant did not reach the stage of pregnancy assessment zero values were imputed. The pregnancy rate is 100 times the number of participants with pregnancies detected, divided by the number of participants assessed.	Two weeks after embryo transfer (up to 1 year)
Secondary	Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Embryo Transfer	Biochemical pregnancy was assessed for participants who had embryo transfer by measuring serum or urinary hCG. The pregnancy rate is 100 times the number of participants with pregnancies detected, divided by the number of participants assessed.	Two weeks after embryo transfer (up to 1 year)