In Vitro FertilizationPhase 3NCT00696800
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)
A Phase 3 study testing Corifollitropin alfa, RecFSH / Follitropin beta (Days 1 to 7) and RecFSH / Follitropin beta (Days 8 to hCG) in people with In Vitro Fertilization, run by Organon and Co.
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. Read more about this study
- Who is it for?
- Ages 18 to 36 years, women only
- Conditions the study is for
- In Vitro Fertilization
- What is being tested?
- Corifollitropin alfa, RecFSH / Follitropin beta (Days 1 to 7) and RecFSH / Follitropin beta (Days 8 to hCG)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,509 participants
- Where
- No sites listed yet
- Study dates
- 27 Jun 2006to 15 Jan 2008
- 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 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.
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 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);
Show all 22Show 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/ 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.
About this study
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
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.
Read the detailed 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.
- Conditions
- In Vitro Fertilization
- Being tested
- Corifollitropin alfa, RecFSH / Follitropin beta (Days 1 to 7), Placebo Corifollitropin alfa, Placebo RecFSH / follitropin beta, RecFSH / Follitropin beta (Days 8 to hCG)
- Keywords
- Infertility, Pharmacological effect of drugs, Hormones, Hormone substitutes and hormone antagonists, Pharmacological actions, Randomized, Multi-center, Multi-national, Double-blind, Active-controlled, Non-inferiority
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Corifollitropin alfaDrug
Also called MK-8962, SCH 900962, Org 36286
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.
RecFSH / Follitropin beta (Days 1 to 7)Biological
Also called Puregon / Follistim AQ Cartridge
Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
Placebo Corifollitropin alfaDrug
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 betaDrug
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.
RecFSH / Follitropin beta (Days 8 to hCG)Biological
Also called Puregon / Follistim AQ Cartridge
From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG.
GanirelixDrug
Also called Orgalutran/ Ganirelix Acetate Injection
On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG
hCGBiological
Also called Pregnyl / urinary 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
ProgesteroneBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 150 µg Corifollitropin Alfa | Experimental | Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses. Receives: Drug: Corifollitropin alfa; Drug: Placebo RecFSH / follitropin beta; Biological: RecFSH / Follitropin beta (Days 8 to hCG); Drug: Ganirelix; Biological: hCG; Biological: Progesterone |
| 200 IU recFSH | Active comparator | Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses. Receives: Biological: RecFSH / Follitropin beta (Days 1 to 7); Drug: Placebo Corifollitropin alfa; Biological: RecFSH / Follitropin beta (Days 8 to hCG); Drug: Ganirelix; Biological: hCG; Biological: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Assessed at least 10 weeks after embryo transfer (up to 1 year)
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.
Measured: Up to 36 hours after administration of hCG (up to 1 year)
Secondary outcomes (21)
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.
Measured: From Day 1 to day of hCG treatment (up to 1 year)
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.
Measured: From Day 8 to Day of hCG treatment (up to 1 year)
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.
Measured: Up to day of hCG treatment (up to 1 year)
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.
Measured: Up to day of hCG treatment (up to 1 year)
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.
Measured: Up to day of hCG treatment (up to 1 year)
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
Measured: Up to day of hCG treatment (up to 1 year)
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
Measured: Up to day of hCG treatment (up to 1 year)
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.
Measured: On Day 1 of treatment (up to 1 year)
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.
Measured: On Day 5 of treatment (up to 1 year)
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.
Measured: On Day 8 of treatment (up to 1 year)
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.
Measured: Day of HCG treatment (up to 1 year)
Number of Cumulus-oocyte-complexes
Prior to IVF the mean number of cumulus-oocyte-complexes used for IVF was assessed
Measured: Up to 36 hours after administration of hCG (up to 1 year)
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
Measured: Up to 36 hours after administration of hCG (up to 1 year)
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
Measured: Up to 18 hours after start of fertilization (up to 1 year)
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.
Measured: Post fertilization Day 3 (up to 1 year)
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.
Measured: Post fertilization Day 3 (up to 1 year)
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.
Measured: Up to 6 weeks after embryo transfer (up to 1 year)
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.
Measured: Up to day of miscarriage (up to 1 year)
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.
Measured: Up to day of miscarriage (up to 1 year)
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.
Measured: Two weeks after embryo transfer (up to 1 year)
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.
Measured: Two weeks after embryo transfer (up to 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2008 (estimated)
- Study start27 Jun 2006
- Primary completion19 Nov 2007
- Study completion15 Jan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for In Vitro FertilizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 1,509 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696800
- Sponsor's protocol ID
- P05787
- Other IDs
- 2004-004771-11, 38819, 8962-011, 2004
- Status last verified
- Feb 2022
- First submitted
- 11 Jun 2008
- Last updated
- 20 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016 Nov;31(11):2554-2560. doi: 10.1093/humrep/dew213. Epub 2016 Sep 12.
PubMed 27619773Zandvliet 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 26991902Griesinger 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 26950065Broekmans FJ, Verweij PJ, Eijkemans MJ, Mannaerts BM, Witjes H. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2014 Aug;29(8):1688-97. doi: 10.1093/humrep/deu090. Epub 2014 Jun 5.
PubMed 24903202Leader A, Devroey P, Witjes H, Gordon K. Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the Engage trial. Reprod Biol Endocrinol. 2013 Jun 11;11:52. doi: 10.1186/1477-7827-11-52.
PubMed 23758821Fauser BC, Alper MM, Ledger W, Schoolcraft WB, Zandvliet A, Mannaerts BM; Engage Investigators. Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF. Reprod Biomed Online. 2010 Nov;21(5):593-601. doi: 10.1016/j.rbmo.2010.06.032. Epub 2010 Jun 30.
PubMed 20843746Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC; ENGAGE Investigators. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009 Dec;24(12):3063-72. doi: 10.1093/humrep/dep291. Epub 2009 Aug 14.
PubMed 19684043
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00696800
- Acronym / sponsor ID
- P05787
- Conditions
- In Vitro Fertilization
- Keywords
- Infertility, Pharmacological effect of drugs, Hormones, Hormone substitutes and hormone antagonists, Pharmacological actions, Randomized, Multi-center, Multi-national
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,509 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2006 (actual)
- Primary completion
- 19 Nov 2007 (actual)
- Study completion
- 15 Jan 2008 (actual)
- First posted
- 13 Jun 2008 (estimated)
- Results
- Posted 21 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 150 µg Corifollitropin Alfa | Experimental | Drug: Corifollitropin alfa, Drug: Placebo RecFSH / follitropin beta, Biological: RecFSH / Follitropin beta (Days 8 to hCG), Drug: Ganirelix, Biological: hCG, Biological: ProgesteroneParticipants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles >= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses. |
| 200 IU recFSH | Active comparator | Biological: RecFSH / Follitropin beta (Days 1 to 7), Drug: Placebo Corifollitropin alfa, Biological: RecFSH / Follitropin beta (Days 8 to hCG), Drug: Ganirelix, Biological: hCG, Biological: ProgesteroneParticipants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles >= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses. |
Who may qualify
- Ages
- 18 to 36 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (22 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Corifollitropin alfaAlso: MK-8962, SCH 900962, Org 36286On 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. | Drug | 150 µg Corifollitropin Alfa |
| RecFSH / Follitropin beta (Days 1 to 7)Also: Puregon / Follistim AQ CartridgeDaily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7. | Biological | 200 IU recFSH |
| Placebo Corifollitropin alfaPre-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. | Drug | 200 IU recFSH |
| Placebo RecFSH / follitropin betaIdentical 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. | Drug | 150 µg Corifollitropin Alfa |
| RecFSH / Follitropin beta (Days 8 to hCG)Also: Puregon / Follistim AQ CartridgeFrom Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG. | Biological | 150 µg Corifollitropin Alfa, 200 IU recFSH |
| GanirelixAlso: Orgalutran/ Ganirelix Acetate InjectionOn Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG | Drug | 150 µg Corifollitropin Alfa, 200 IU recFSH |
| hCGAlso: Pregnyl / urinary hCGWhen 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 | Biological | 150 µg Corifollitropin Alfa, 200 IU recFSH |
| ProgesteroneOn 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. | Biological | 150 µg Corifollitropin Alfa, 200 IU recFSH |
Primary outcome
Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate)
Time frame: Assessed at least 10 weeks after embryo transfer (up to 1 year)
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.
Mean Number of Oocytes Retrieved
Time frame: Up to 36 hours after administration of hCG (up to 1 year)
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.
21 secondary outcomes
Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 1
Time frame: From Day 1 to day of hCG treatment (up to 1 year)
Median Amount of Recombinant FSH Needed to Induce Multifollicular Development Starting at Day 8
Time frame: From Day 8 to Day of hCG treatment (up to 1 year)
Serum FSH Levels During Stimulation
Time frame: Up to day of hCG treatment (up to 1 year)
Serum Luteinizing Hormone (LH) Levels During Stimulation
Time frame: Up to day of hCG treatment (up to 1 year)
Serum Estradiol (E2) Levels During Stimulation
Time frame: Up to day of hCG treatment (up to 1 year)
Serum Progesterone (P) Levels During Stimulation
Time frame: Up to day of hCG treatment (up to 1 year)
Serum Inhibin-B Levels During Stimulation
Time frame: Up to day of hCG treatment (up to 1 year)
Number of Follicles Categorized by Size on Stimulation Day 1
Time frame: On Day 1 of treatment (up to 1 year)
Number of Follicles Categorized by Size on Stimulation Day 5
Time frame: On Day 5 of treatment (up to 1 year)
Number of Follicles Categorized by Size on Stimulation Day 8
Time frame: On Day 8 of treatment (up to 1 year)
Number of Follicles Categorized by Size on the Day of hCG
Time frame: Day of HCG treatment (up to 1 year)
Number of Cumulus-oocyte-complexes
Time frame: Up to 36 hours after administration of hCG (up to 1 year)
Number of Oocytes Assessed Prior to Intracytoplasmic Sperm Injection (ICSI)
Time frame: Up to 36 hours after administration of hCG (up to 1 year)
Percentage of Fertilized Oocytes (Fertilization Rate)
Time frame: Up to 18 hours after start of fertilization (up to 1 year)
Number of Embryos Obtained on Day 3 Categorized by Quality
Time frame: Post fertilization Day 3 (up to 1 year)
Number of Embryos Transferred on Day 3
Time frame: Post fertilization Day 3 (up to 1 year)
Percentage of Gestational Sacs (Implantation Rate)
Time frame: Up to 6 weeks after embryo transfer (up to 1 year)
Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Clinical Pregnancy
Time frame: Up to day of miscarriage (up to 1 year)
Percentage of Participants With a Miscarriage (Miscarriage Rate) Per Vital Pregnancy
Time frame: Up to day of miscarriage (up to 1 year)
Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Attempt
Time frame: Two weeks after embryo transfer (up to 1 year)
Percentage of Participants With a Biochemical Pregnancy (Pregnancy Rate) Per Embryo Transfer
Time frame: Two weeks after embryo transfer (up to 1 year)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27619773Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016 Nov;31(11):2554-2560. doi: 10.1093/humrep/dew213. Epub 2016 Sep 12.
- Derived from this study: PubMed 26991902Zandvliet 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.
- Derived from this study: PubMed 26950065Griesinger 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.
- Derived from this study: PubMed 24903202Broekmans FJ, Verweij PJ, Eijkemans MJ, Mannaerts BM, Witjes H. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2014 Aug;29(8):1688-97. doi: 10.1093/humrep/deu090. Epub 2014 Jun 5.
- Derived from this study: PubMed 23758821Leader A, Devroey P, Witjes H, Gordon K. Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the Engage trial. Reprod Biol Endocrinol. 2013 Jun 11;11:52. doi: 10.1186/1477-7827-11-52.
- Derived from this study: PubMed 20843746Fauser BC, Alper MM, Ledger W, Schoolcraft WB, Zandvliet A, Mannaerts BM; Engage Investigators. Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF. Reprod Biomed Online. 2010 Nov;21(5):593-601. doi: 10.1016/j.rbmo.2010.06.032. Epub 2010 Jun 30.
- Derived from this study: PubMed 19684043Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC; ENGAGE Investigators. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009 Dec;24(12):3063-72. doi: 10.1093/humrep/dep291. Epub 2009 Aug 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Corifollitropin alfa, RecFSH / Follitropin beta (Days 1 to 7) and RecFSH / Follitropin beta (Days 8 to hCG) in people with In Vitro Fertilization, 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 22 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 20 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 21 Aug 2014). 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?
Percentage of Participants With an Ongoing Pregnancy (Ongoing Pregnancy Rate) (time frame: Assessed at least 10 weeks after embryo transfer (up to 1 year)). The study lists 2 primary outcomes in all. 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 NCT00696800, which also lists 7 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 20 Jun 2024.