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) (Ensure)

February 1, 2022 updated by: Organon and Co

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 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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

397

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 34 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
100 µg corifollitropin alfa subcutaneous (SC) injection
Other Names:
  • Org 36286
GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day
hCG 5,000 IU or 10,000 IU administered SC
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 administered at the equivalent volume of 150 IU/day.
Open-label recFSH administered up to a maximum dose of 200 IU/day.
Active Comparator: 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.
GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day
hCG 5,000 IU or 10,000 IU administered SC
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.
Open-label recFSH administered up to a maximum dose of 200 IU/day.
150 IU recFSH SC injection
Other Names:
  • recFSH (Puregon/Follistim AQ Cartridge)
Single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Cumulus-oocyte-complexes Retrieved, Per Attempt
Time Frame: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Dose of recFSH Administered
Time Frame: One COS cycle (up to a maximum total duration of 19 stimulation days)
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)
Total Dose of recFSH Administered From Day 8 Onwards
Time Frame: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)
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)
Number of Days Treated With recFSH
Time Frame: One COS cycle (up to a maximum total duration of 19 stimulation days)
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)
Total Duration of Stimulation (Days)
Time Frame: One COS cycle (up to a maximum total duration of 19 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)
Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection)
Time Frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
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)
Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)
Time Frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
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)
Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)
Time Frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
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)
Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection)
Time Frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
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)
Serum Inhibin-B Levels (Restricted to Participants With hCG Injection)
Time Frame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
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)
Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration
Time Frame: Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including 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)
Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only)
Time Frame: Up to 36 hours after administration of hCG
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
Fertilization Rate
Time Frame: Up to 10 weeks after ET
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
Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI)
Time Frame: Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)
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)
Implantation Rate for Participants With ET
Time Frame: Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)
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)
Number of Participants With Miscarriages
Time Frame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
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)
Number of Participants With Pregnancies
Time Frame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 28, 2006

Primary Completion (Actual)

July 7, 2007

Study Completion (Actual)

November 15, 2007

Study Registration Dates

First Submitted

June 18, 2008

First Submitted That Met QC Criteria

June 19, 2008

First Posted (Estimate)

June 20, 2008

Study Record Updates

Last Update Posted (Actual)

February 3, 2022

Last Update Submitted That Met QC Criteria

February 1, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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