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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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)

Short name Ensure

NCTNCT00702845 (opens ClinicalTrials.gov in a new tab)Other idP05690Other id2006-003811-36Other id107012
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
397 participants (actual)
Sponsor
Organon and Co · Industry
Design
Randomized · Double masking
Countries
Not stated
Start
28 Dec 2006
Primary completion
7 Jul 2007
Completion
15 Nov 2007
First posted
20 Jun 2008 (estimated)
Last update posted
18 Jun 2024
Conditions
Infertility

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
200620072008
  1. Ph 3

    Ensure

    NCT00702845

    28 Dec 2006 to 15 Nov 2007

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • corifollitropin alfa (Org 36286)Drug
  • recFSH (follitropin beta)Drug
  • gonadatropin releasing hormone (GnRH) antagonist (ganirelix)Drug
  • human chorion gonadatropin (hCG)Drug
  • progesteroneBiological
  • placebo-recFSH (follitropin alfa)Drug
  • placebo-corifollitropin alfaDrug
  • open-label recFSHBiological

Arms2

  • 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.

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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)

    Registry description

    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.

Secondary outcomes(16)

  1. Total Dose of recFSH Administered

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

    Registry description

    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).

  2. 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)

    Registry description

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

  3. Number of Days Treated With recFSH

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

    Registry description

    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).

  4. Total Duration of Stimulation (Days)

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

    Registry description

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

  5. 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)

    Registry description

    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.

  6. 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)

    Registry description

    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.

  7. 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)

    Registry description

    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.

  8. 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)

    Registry description

    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.

  9. 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)

    Registry description

    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.

  10. 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)

    Registry description

    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.

  11. 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

    Registry description

    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).

  12. Fertilization Rate

    Time frame · Up to 10 weeks after ET

    Registry description

    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.

  13. 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)

    Registry description

    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.

  14. Implantation Rate for Participants With ET

    Time frame · Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)

    Registry description

    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%.

  15. Number of Participants With Miscarriages

    Time frame · Up to 10 weeks after ET (up to a maximum of 14 weeks)

    Registry description

    A miscarriage, also known as a "spontaneous abortion," was defined as the loss of a fetus without induction or instrumentation.

  16. Number of Participants With Pregnancies

    Time frame · Up to 10 weeks after ET (up to a maximum of 14 weeks)

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)

Number of Cumulus-oocyte-complexes Retrieved, Per Attempt

GroupValue (Number of cumulus-oocyte-complexes)Spread
100 μg Corifollitropin Alfa13.37.3
150 IU recFSH10.65.9
Secondary and other outcome results(7)
Secondary outcomeMedian· One COS cycle (up to a maximum total duration of 19 stimulation days)

Total Dose of recFSH Administered

GroupValue (International Unit (IU))
100 μg Corifollitropin Alfa300.0
150 IU recFSH1350.0
Secondary outcomeMedian· 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 Administered From Day 8 Onwards

GroupValue (International Unit (IU))
100 μg Corifollitropin Alfa300.0
150 IU recFSH275.0
Secondary outcomeMedian· One COS cycle (up to a maximum total duration of 19 stimulation days)

Number of Days Treated With recFSH

GroupValue (Days)
100 μg Corifollitropin Alfa2.0
150 IU recFSH9.0
Secondary outcomeMedian· One COS cycle (up to a maximum total duration of 19 stimulation days)

Total Duration of Stimulation (Days)

GroupValue (Days)
100 μg Corifollitropin Alfa9.0
150 IU recFSH9.0
Secondary outcomeMedian· Predose up to 2 weeks after ET (up to maximum of 6 weeks)

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

GroupValue (IU/L)Spread
100 μg Corifollitropin Alfa6.461.84
150 IU recFSH6.511.89
Secondary outcomeMedian· Predose up to 2 weeks after ET (up to maximum of 6 weeks)

Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)

GroupValue (IU/L)Spread
100 μg Corifollitropin Alfa4.461.81
150 IU recFSH4.121.94
Secondary outcomeMedian· Predose up to 2 weeks after ET (up to maximum of 6 weeks)

Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)

GroupValue (pmol/L)Spread
100 μg Corifollitropin Alfa118.1753.18
150 IU recFSH120.3871.07

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
100 μg Corifollitropin AlfaParticipants received a single SC injection of corifollitropin alfa 100 μg (Org 36286) on Day 2 or 3 of the menstrual cycle and daily placebo-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 hCG administration. Participants also received 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 IM), starting on day of OPU and continuing for at least 6 weeks or up to menses.–20 / 268107 / 268
150 IU recFSHParticipants 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.–9 / 12955 / 129

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultCorifollitropin 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. PMID 20483664
  • DerivedZandvliet 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. PMID 26991902
  • DerivedGriesinger 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. PMID 26950065

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 36 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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