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)

NCT00702845 | Completed Phase 3 Results

• 3 other identifiers: P056902006-003811-36107012
• Study Type: interventional
• Target: 397
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Infertility

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (16)

• Total Dose of recFSH Administered

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

• Total Dose of recFSH Administered From Day 8 Onwards

  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

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

• Total Duration of Stimulation (Days)

  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)

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

Study Arms (2)

corifollitropin alfa 100 µg

EXPERIMENTAL

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.

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 IU

ACTIVE COMPARATOR

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.

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

Interventions

corifollitropin alfa (Org 36286) DRUG

100 µg corifollitropin alfa subcutaneous (SC) injection

Also known as: Org 36286

corifollitropin alfa 100 µg

recFSH (follitropin beta) DRUG

150 IU recFSH SC injection

Also known as: recFSH (Puregon/Follistim AQ Cartridge)

recFSH 150 IU

gonadatropin releasing hormone (GnRH) antagonist (ganirelix) DRUG

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

corifollitropin alfa 100 µg; recFSH 150 IU

human chorion gonadatropin (hCG) DRUG

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

corifollitropin alfa 100 µg; recFSH 150 IU

progesterone BIOLOGICAL

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.

corifollitropin alfa 100 µg; recFSH 150 IU

placebo-recFSH (follitropin alfa) DRUG

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

corifollitropin alfa 100 µg

placebo-corifollitropin alfa DRUG

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

recFSH 150 IU

open-label recFSH BIOLOGICAL

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

corifollitropin alfa 100 µg; recFSH 150 IU

Eligibility Criteria

• Age: 18 Years - 36 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

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 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);

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (3)

• 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.

  PMID: 20483664 RESULT

• 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.

  PMID: 26991902 DERIVED

• 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.

  PMID: 26950065 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

follicle stimulating hormone, human, with HCG C-terminal peptide; follitropin beta; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; ganirelix; Progesterone; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chorionic Gonadotropin; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

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 18, 2008
• First Posted: June 20, 2008
• Study Start: December 28, 2006
• Primary Completion: July 7, 2007
• Study Completion: November 15, 2007
• Last Updated: June 18, 2024
• Results First Posted: April 27, 2015

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share