Corifollitropin Alfa in Participants Undergoing Repeated Controlled Ovarian Stimulation (COS) Cycles Using a Multiple Dose Gonadatropin Releasing Hormone (GnRH) Antagonist Protocol (Study 38825)(P05714)

NCT00696878 | Completed Phase 3 Results

• 4 other identifiers: P05714MK-8962-007388252004-004966-34
• Study Type: interventional
• Target: 682
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of the trial is to assess the non-immunogenicity and safety of corifollitropin alfa (also known as Org 36286, SCH 900962 and MK-8962) in participants undergoing repeated COS cycles using a multiple dose GnRH antagonist protocol.

Conditions

In Vitro Fertilization

Keywords

Infertility; Pharmacological effects of drugs; Hormones, Hormone Substitutes and Hormone Antagonists; Pharmacological Actions; Multi-center

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With Clinically Relevant Immunogenicity

  Serum samples obtained pre-dose and at 2 weeks after embryo transfer (ET), or at cycle discontinuation and 2-3 weeks after cycle discontinuation if cycle was stopped before ET was performed, were analyzed for presence of anti-corifollitropin alfa antibodies using screening and confirmatory tests. If a participant was confirmed to have anti-corifollitropin alfa antibody present in a post dose sample according to these tests, review of adverse events (AEs) in the participant was performed. The sample was also tested to evaluate whether the antibody appeared to have neutralizing activity that would interfere with the study drug biological effect. A participant was determined to have clinically relevant immunogenicity if the participant had a confirmed post dose anti-corifollitropin alfa antibody test result accompanied by clinical signs of immunogenicity (e.g., hypersensitivity reaction), considering also the results of the test for neutralizing activity of any antibody present.

  Pre-dose (Stimulation Day 1) and up to approximately 40 days post dose in each treatment cycle

• Local Tolerance at Injection Site: Number of Participants With no Event of Itching and With Mild, Moderate and Severe Itching in Any of 3 Treatment Cycles

  At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of itching. A participant with an event was counted once in this analysis.

  30 minutes post dose in each treatment cycle

• Local Tolerance at Injection Site: Number of Participants With no Event of Pain and With Mild, Moderate and Severe Pain in Any of 3 Treatment Cycles

  At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of pain. A participant with an event was counted once in this analysis.

  30 minutes post dose in each treatment cycle

• Local Tolerance at Injection Site: Number of Participants With no Event of Redness and With Mild, Moderate and Severe Redness in Any of 3 Treatment Cycles

  At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of redness. A participant with an event was counted once in this analysis.

  30 minutes post dose in each treatment cycle

• Local Tolerance at Injection Site: Number of Participants With no Event of Swelling and With Mild, Moderate and Severe Swelling in Any of 3 Treatment Cycles

  At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results for the assessment of swelling. A participant with an event was counted once in this analysis.

  30 minutes post dose in each treatment cycle

• Local Tolerance at Injection Site Overall Summary: Number of Participants With no Local Tolerance Event (Itching, Pain, Redness or Swelling) and With a Mild, Moderate and Severe Local Tolerance Event in Any of 3 Treatment Cycles

  At 30 minutes after dosing in each treatment cycle, the corifollitropin alfa injection site was assessed for the presence of itching, pain, redness and swelling, each of which was scored as none (no event), mild, moderate or severe. This measure reports results considering the occurrence of any of the defined local tolerance events. A participant with an event was counted once in this analysis.

  30 minutes post dose in each treatment cycle

• Number of Participants With AEs

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  Up to approximately 26 months after first dose of corifollitropin alfa

• Number of Participants With Serious AEs (SAEs)

  An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. SAEs that occurred in fetuses or infants during the study period are included in this summary of SAEs, and are allocated to the associated study participant who was administered corifollitropin alfa.

  Up to approximately 26 months after first dose of corifollitropin alfa

• Number of Participants With Moderate to Severe Ovarian Hyperstimulation Syndrome (OHSS)

  OHSS was classified on study based on a slightly modified WHO Scientific Group (1973) classification: Grade I (mild) = characterized by excessive steroid secretion and ovarian enlargement (5-7 cm). Abdominal discomfort, including abdominal pain, is present. Grade II (moderate) = characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea. Grade III (severe) = characterized by enlarged cystic ovaries (ovary size \>10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause haemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena.

  Up to approximately 1 month after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle

Secondary Outcomes (60)

• Amount of (Rec)FSH Needed From Stimulation Day 8 Onwards to Reach the Criterion for Administration of (Rec)hCG

  Stimulation Day 8 to day of (rec)hCG administration (approximately Stimulation Day 10), within a treatment cycle

• Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 1

  Stimulation Day 1 in Treatment Cycle 1

• Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 2

  Stimulation Day 1 in Treatment Cycle 2

• Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 1 During Treatment Cycle 3

  Stimulation Day 1 in Treatment Cycle 3

• Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 5 or 6 During Treatment Cycle 1

  Stimulation Day 5 or 6 in Treatment Cycle 1

Study Arms (1)

Corifollitropin alfa 150 µg

EXPERIMENTAL

Up to 3 COS cycles (also called treatment cycles) were performed, each including the following: A single injection of 150 µg corifollitropin alfa was administered on Day 2 or 3 of the menstrual cycle (Stimulation Day 1). Administration of GnRH antagonist (0.25 mg/day) started on Stimulation Day 5 or 6 and continued through day of administration of recombinant Human Chorion Gonadotropin (\[rec\]hCG) (5,000-10,000 IU/250 µg). Administration of (rec)hCG occurred when 3 follicles ≥17 mm were observed on ultrasound scan (USS). Daily dosing with Follicle Stimulating Hormone (FSH) (not to exceed 225 IU/day) began on Stimulation Day 8 and continued up to day of (rec)hCG administration. Progesterone for luteal phase support was administered starting on the day of oocyte pick-up (34-36 hours after \[rec\]hCG) and continued for approximately 6 weeks. After COS cycles 1 and 2, Frozen-Thawed Embryo Transfer cycles (up to 3 after each COS cycle) could occur.

Drug: Corifollitropin alfa; Biological: FSH; Biological: GnRH antagonist; Biological: (rec)hCG; Drug: Progesterone

Interventions

Corifollitropin alfa DRUG

Corifollitropin alfa 150 µg administered as a single subcutaneous dose.

Also known as: Org 36286, SCH 900962, MK-8962

Corifollitropin alfa 150 µg

FSH BIOLOGICAL

FSH administerd subcutaneously at a dose not to exceed 225 IU/day.

Corifollitropin alfa 150 µg

GnRH antagonist BIOLOGICAL

GnRH antagonist administered subcutaneously at a dose of 0.25 mg/day.

Corifollitropin alfa 150 µg

(rec)hCG BIOLOGICAL

(rec)hCG administered subcutaneously at a dose of 5,000-10,000 IU/250 µg.

Corifollitropin alfa 150 µg

Progesterone DRUG

Progesterone administered vaginally at a dose of at least 600 mg/day.

Corifollitropin alfa 150 µg

Eligibility Criteria

• Age: 18 Years - 39 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 \<=39 years of age at the time of signing informed consent;
• Body weight \> 60 kg and body mass index (BMI) \>=18 and \<=29 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 history of ovarian hyperstimulation syndrome (OHSS);
• History of or current polycystic ovary syndrome (PCOS);
• More than 20 basal antral follicles (size: \<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 hydrosalpinx (visible on USS);
• More than three unsuccessful COS cycles since the last established ongoing pregnancy (if applicable);
• History of non- or low ovarian response to FSH/human menopausal gonadotrophin (hMG) treatment;
• FSH \> 12 IU/L or luteinizing hormone (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, including abnormal cervical smear (Papanicolaou \[PAP\]\>=III, cervical intraepithelial neoplasia \[CIN\]\>=1);
• Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts) or GnRH antagonists (e.g. hypersensitivity, pregnancy/lactation);
• Recent history of or current epilepsy, human immunodeficiency virus (HIV) infection, thrombophilia, diabetes or cardiovascular, gastro-intestinal, hepatic, renal, or pulmonary disease;
• Abnormal karyotyping of the participant or her partner (if karyotyping is performed);
• History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
• Previous use of corifollitropin alfa;

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (4)

• 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

• Rombauts L, Lambalk CB, Schultze-Mosgau A, van Kuijk J, Verweij P, Gates D, Gordon K, Griesinger G. Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin-releasing hormone antagonist protocol. Fertil Steril. 2015 Oct;104(4):884-890.e2. doi: 10.1016/j.fertnstert.2015.06.027. Epub 2015 Jul 15.

  PMID: 26187300 DERIVED

• Norman RJ, Zegers-Hochschild F, Salle BS, Elbers J, Heijnen E, Marintcheva-Petrova M, Mannaerts B; Trust Investigators. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity. Hum Reprod. 2011 Aug;26(8):2200-8. doi: 10.1093/humrep/der163. Epub 2011 May 27.

  PMID: 21622693 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

follicle stimulating hormone, human, with HCG C-terminal peptide; LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; Progesterone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 13, 2008
• Study Start: September 26, 2006
• Primary Completion: February 17, 2009
• Study Completion: May 15, 2009
• Last Updated: June 18, 2024
• Results First Posted: April 23, 2015

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share