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)

Infertility Clinical Trial

— Ensure  

Official title:

A Phase III, Randomized, Double-blind, Active-controlled, Equivalence Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of 100 µg Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation (COS) Using Daily Recombinant FSH (recFSH) as a Reference

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00702845
• Other study ID #: P05690
• Secondary ID: 2006-003811-3610
• Status: Completed
• Phase: Phase 3
• Start date: December 28, 2006
• Est. completion date: November 15, 2007

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: November 15, 2007
• Est. primary completion date: July 7, 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 36 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• corifollitropin alfa (Org 36286)
100 µg corifollitropin alfa subcutaneous (SC) injection
• recFSH (follitropin beta)
150 IU recFSH SC injection
• gonadatropin releasing hormone (GnRH) antagonist (ganirelix)
GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day
• human chorion gonadatropin (hCG)
hCG 5,000 IU or 10,000 IU administered SC

Biological:
• 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.

Drug:
• placebo-recFSH (follitropin alfa)
Placebo-recFSH administered at the equivalent volume of 150 IU/day.
• placebo-corifollitropin alfa
Single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle.

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & Publications (1)

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. Erratum In: Reprod — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
Secondary	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).	One COS cycle (up to a maximum total duration of 19 stimulation days)
Secondary	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).	Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)
Secondary	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).	One COS cycle (up to a maximum total duration of 19 stimulation days)
Secondary	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.	One COS cycle (up to a maximum total duration of 19 stimulation days)
Secondary	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.	Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Secondary	Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)	Blood samples for assessment of serum LH 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.	Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Secondary	Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)	Blood samples for assessment of serum E2 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.	Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Secondary	Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection)	Blood samples for assessment of serum P 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.	Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Secondary	Serum Inhibin-B Levels (Restricted to Participants With hCG Injection)	Blood samples for assessment of serum inhibin-B 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.	Predose up to 2 weeks after ET (up to maximum of 6 weeks)
Secondary	Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration	For each participant, the number of follicles =11 mm, =15 mm, and =17 mm, documented by ultrasonography on defined days during the treatment cycle, was calculated.	Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration)
Secondary	Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only)	The number of oocytes used for ICSI was assessed and categorized based on their quality (i.e., metaphase I oocytes, metaphase II oocytes, and germinal vesicles stage oocytes).	Up to 36 hours after administration of hCG
Secondary	Fertilization Rate	Fertilization rate, defined as 100 times the ratio of the number of fertilized 2 pronuclei (PN) oocytes obtained and the number of oocytes incubated, was tabulated for each treatment group.	Up to 10 weeks after ET
Secondary	Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI)	Embryo quality was rated Grade 1, 2, 3, or other. Grade 1 represented excellent quality; Grade 2 good quality; Grade 3 fair quality. "Other" grade embryos were those that did not qualify as Grade 1, 2, or 3.	Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)
Secondary	Implantation Rate for Participants With ET	The implantation rate was defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan (USS) after ET divided by the number of embryos transferred (per participant), maximized to 100%.	Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)
Secondary	Number of Participants With Miscarriages	A miscarriage, also known as a "spontaneous abortion," was defined as the loss of a fetus without induction or instrumentation.	Up to 10 weeks after ET (up to a maximum of 14 weeks)
Secondary	Number of Participants With Pregnancies	A Biochemical Pregnancy was defined as a pregnancy proven by a biochemical pregnancy test. (Participants not having a positive biochemical pregnancy test result, but with an ultrasound showing at least one gestational sac were counted as having a biochemical pregnancy.) A Clinical Pregnancy was defined as the presence of at least one gestational sac as assessed by an USS scan. A Vital Pregnancy was considered the presence of at least one fetus with heart activity as assessed by USS. An Ongoing Pregnancy was defined as the presence of at least one fetus with heart activity at least 10 weeks after ET as assessed by USS or Doppler, or confirmed by live birth.	Up to 10 weeks after ET (up to a maximum of 14 weeks)