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 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
4 other identifiers
interventional
1,509
0 countries
N/A
Brief 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. The primary hypothesis is that a single injection of Corifollitropin Alfa is non-inferior to daily treatment with recFSH in initiating multifollicular growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2006
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 27, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 19, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
January 15, 2008
CompletedFirst Submitted
Initial submission to the registry
June 11, 2008
CompletedFirst Posted
Study publicly available on registry
June 13, 2008
CompletedResults Posted
Study results publicly available
August 21, 2014
CompletedJune 20, 2024
February 1, 2022
1.4 years
June 11, 2008
August 6, 2014
June 5, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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.
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
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
From Day 8 to Day of hCG treatment (up to 1 year)
Serum FSH Levels During Stimulation
Up to day of hCG treatment (up to 1 year)
Serum Luteinizing Hormone (LH) Levels During Stimulation
Up to day of hCG treatment (up to 1 year)
Serum Estradiol (E2) Levels During Stimulation
Up to day of hCG treatment (up to 1 year)
- +16 more secondary outcomes
Study Arms (2)
150 µg Corifollitropin Alfa
EXPERIMENTALParticipants 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 COMPARATORParticipants 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.
Interventions
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.
Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7.
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.
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.
From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG.
On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of 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
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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);
- 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;
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Organon and Colead
Related Publications (7)
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.
PMID: 27619773DERIVEDZandvliet 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: 26991902DERIVEDGriesinger 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: 26950065DERIVEDBroekmans 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.
PMID: 24903202DERIVEDLeader 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.
PMID: 23758821DERIVEDFauser 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.
PMID: 20843746DERIVEDDevroey 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.
PMID: 19684043DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 11, 2008
First Posted
June 13, 2008
Study Start
June 27, 2006
Primary Completion
November 19, 2007
Study Completion
January 15, 2008
Last Updated
June 20, 2024
Results First Posted
August 21, 2014
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share