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InfertilityPhase 3EnsureNCT00702845

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)

A Phase 3 study testing corifollitropin alfa (Org 36286), recFSH (follitropin beta) and gonadatropin releasing hormone (GnRH) antagonist (ganirelix) in people with Infertility, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 36 years, women only
Conditions the study is for
Infertility
What is being tested?
corifollitropin alfa (Org 36286), recFSH (follitropin beta) and gonadatropin releasing hormone (GnRH) antagonist (ganirelix)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
397 participants
Where
No sites listed yet
Study dates
28 Dec 2006to 15 Nov 2007
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 36 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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);
Show all 24Show fewer
  • 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.

About this study

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 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.

Read the 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
Being tested
corifollitropin alfa (Org 36286), recFSH (follitropin beta), gonadatropin releasing hormone (GnRH) antagonist (ganirelix), human chorion gonadatropin (hCG), progesterone
Keywords
In vitro fertilization, Pharmacological effects of drugs, Hormones, Hormone Substitutes and Hormone Antagonists, Pharmacological Actions, Randomized, Multi-center, Multi-national, Double-blind, Active-controlled, Equivalence
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • corifollitropin alfa (Org 36286)Drug

    Also called Org 36286

    100 µg corifollitropin alfa subcutaneous (SC) injection

  • recFSH (follitropin beta)Drug

    Also called recFSH (Puregon/Follistim AQ Cartridge)

    150 IU recFSH SC injection

  • gonadatropin releasing hormone (GnRH) antagonist (ganirelix)Drug

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

  • human chorion gonadatropin (hCG)Drug

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

  • progesteroneBiological

    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)Drug

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

  • placebo-corifollitropin alfaDrug

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

  • open-label recFSHBiological

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

Study groups in NCT00702845
Study groupRoleWhat they receive
corifollitropin alfa 100 µgExperimentalParticipants 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.
Receives: Drug: corifollitropin alfa (Org 36286); Drug: gonadatropin releasing hormone (GnRH) antagonist (ganirelix); Drug: human chorion gonadatropin (hCG); Biological: progesterone; Drug: placebo-recFSH (follitropin alfa); Biological: open-label recFSH
recFSH 150 IUActive comparatorParticipants 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.
Receives: Drug: recFSH (follitropin beta); Drug: gonadatropin releasing hormone (GnRH) antagonist (ganirelix); Drug: human chorion gonadatropin (hCG); Biological: progesterone; Drug: placebo-corifollitropin alfa; Biological: open-label recFSH

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

Secondary outcomes (16)

  1. 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).

    Measured: One COS cycle (up to a maximum total duration of 19 stimulation days)

  2. 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).

    Measured: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)

  3. 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).

    Measured: One COS cycle (up to a maximum total duration of 19 stimulation days)

  4. 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.

    Measured: One COS cycle (up to a maximum total duration of 19 stimulation days)

  5. 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.

    Measured: Predose up to 2 weeks after ET (up to maximum of 6 weeks)

  6. 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.

    Measured: Predose up to 2 weeks after ET (up to maximum of 6 weeks)

  7. 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.

    Measured: Predose up to 2 weeks after ET (up to maximum of 6 weeks)

  8. 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.

    Measured: Predose up to 2 weeks after ET (up to maximum of 6 weeks)

  9. 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.

    Measured: Predose up to 2 weeks after ET (up to maximum of 6 weeks)

  10. 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.

    Measured: Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration)

  11. 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).

    Measured: Up to 36 hours after administration of hCG

  12. 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.

    Measured: Up to 10 weeks after ET

  13. 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.

    Measured: Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)

  14. 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%.

    Measured: Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)

  15. 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.

    Measured: Up to 10 weeks after ET (up to a maximum of 14 weeks)

  16. 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.

    Measured: Up to 10 weeks after ET (up to a maximum of 14 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2008 (estimated)
  2. Study start28 Dec 2006
  3. Primary completion7 Jul 2007
  4. Study completion15 Nov 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00702845
Sponsor's protocol ID
P05690
Other IDs
2006-003811-36, 107012
Acronym
Ensure
Status last verified
Feb 2022
First submitted
18 Jun 2008
Last updated
18 Jun 2024
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 20483664

  • 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.

    PubMed 26991902

  • 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.

    PubMed 26950065

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing corifollitropin alfa (Org 36286), recFSH (follitropin beta) and gonadatropin releasing hormone (GnRH) antagonist (ganirelix) in people with Infertility, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00702845, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.

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