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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00696878
First received: June 11, 2008
Last updated: April 6, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
In Vitro Fertilization
Drug: Corifollitropin alfa
Biological: FSH
Biological: GnRH antagonist
Biological: (rec)hCG
Drug: Progesterone
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Uncontrolled Trial to Assess the Non-immunogenicity and Safety of Org 36286 in Patients Undergoing Repeated Controlled Ovarian Stimulation Cycles Using a Multiple Dose GnRH Antagonist Protocol

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Clinically Relevant Immunogenicity [ Time Frame: Pre-dose (Stimulation Day 1) and up to approximately 40 days post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 30 minutes post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 30 minutes post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 30 minutes post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 30 minutes post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: 30 minutes post dose in each treatment cycle ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With AEs [ Time Frame: Up to approximately 26 months after first dose of corifollitropin alfa ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Serious AEs (SAEs) [ Time Frame: Up to approximately 26 months after first dose of corifollitropin alfa ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Moderate to Severe Ovarian Hyperstimulation Syndrome (OHSS) [ Time Frame: Up to approximately 1 month after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Amount of (Rec)FSH Needed From Stimulation Day 8 Onwards to Reach the Criterion for Administration of (Rec)hCG [ Time Frame: Stimulation Day 8 to day of (rec)hCG administration (approximately Stimulation Day 10), within a treatment cycle ] [ Designated as safety issue: No ]
    Beginning on Stimulation Day 8 of each treatment cycle, (rec)FSH was administered daily until the criteria for administration of (rec)hCG (presence of 3 follicles ≥17 mm documented by ultrasonography) was reached. The total amount of (rec)FSH administered in each participant to reach the criteria for (rec)hCG administration was calculated.

  • 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 [ Time Frame: Stimulation Day 1 in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Stimulation Day 1 in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Stimulation Day 1 in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Stimulation Day 5 or 6 in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    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.

  • 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 2 [ Time Frame: Stimulation Day 5 or 6 in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    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.

  • 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 3 [ Time Frame: Stimulation Day 5 or 6 in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    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.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 1 [ Time Frame: Stimulation Day 8 in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    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.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 2 [ Time Frame: Stimulation Day 8 in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    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.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Stimulation Day 8 During Treatment Cycle 3 [ Time Frame: Stimulation Day 8 in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    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.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 1 [ Time Frame: Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 2 [ Time Frame: Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

  • Number of Follicles ≥11 mm, ≥15 mm and ≥17 mm Documented by Ultrasonography Performed in the Participant on Day of (Rec)hCG Administration During Treatment Cycle 3 [ Time Frame: Day of (rec)hCG administration (approximately Stimulation Day 10) in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    For each participant, the number of follicles ≥11 mm, ≥15 mm and ≥17 mm documented by ultrasonography on the day of (rec)hCG administration during the treatment cycle was recorded.

  • Number of Oocytes Retrieved in a Participant Among Entire Study Population [ Time Frame: Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), within a treatment cycle ] [ Designated as safety issue: No ]
    Oocyte retrieval, also known as oocyte pick-up, is a technique used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The number of oocytes retrieved, per participant, is summarized.

  • Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 1 [ Time Frame: Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 1. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

  • Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 2 [ Time Frame: Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 2. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

  • Quality of Oocytes Assessed Prior to Planned ICSI in Treatment Cycle 3 [ Time Frame: Day of oocyte pick-up, 34-36 hours after (rec)hCG administration (approximately Stimulation Day 10), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    This measure summarizes results of assessment of the quality of oocytes performed following oocyte retrieval, among participants scheduled for ICSI in Treatment Cycle 3. For oocytes obtained from each participant, the number in each of 3 stages of oocyte development were determined. The earliest phase is the germinal vesicles stage, during which the immature oocyte appears as a large vesicular nucleus. Metaphase I is an intermediate stage during which the vesicles have broken down and the polar body has not yet formed; the oocyte is still immature. Metaphase II is the mature oocyte and is indicated by the presence of the polar body. Rating of quality for usefulness in ICSI follows the order metaphase II (best quality), metaphase I (lesser quality) and germinal vesicles stage (poorest quality). Only metaphase II oocytes can be fertilized. Metaphase I oocytes can develop in vitro to metaphase II oocytes. Germinal vesicles stage oocytes are the least useful for ICSI procedures.

  • Number of Fertilized Oocytes Obtained in Treatment Cycle 1 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of pronuclei (PN) present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained in Treatment Cycle 2 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained in Treatment Cycle 3 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 1 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 2 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Frozen in Treatment Cycle 3 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ICSI procedure that were cryopreserved (frozen) for possible later use, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 1 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 2 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Number of Fertilized Oocytes Obtained That Were Used for Embryo Development in Treatment Cycle 3 [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    This measure presents the number of fertilized oocytes obtained per participant from the IVF or ISCI procedure that were used for embryo development, by category of number of PN present: 0 PN, 1 PN, 2 PN, ≥3 PN, other (fertilized oocyte that was not placed in PN category). Normal fertilized ooctyes have 2 pronuclei (2 PN).

  • Fertilization Rate [ Time Frame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle ] [ Designated as safety issue: No ]
    The fertilization rate (in percent) is defined as 100 times the ratio of the number of fertilized 2 PN oocytes obtained and the number of oocytes that was used for fertilization, per participant.

  • Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 1 [ Time Frame: Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 2 [ Time Frame: Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number and Quality of Embryos Obtained at Day 3 After Oocyte Pick-up in Treatment Cycle 3 [ Time Frame: Day 3 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    At Day 3 after oocyte pick-up, embryos obtained from IVF or ISCI process for each participant were counted and quality was assessed. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number of Embryos Transferred [ Time Frame: At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), within a treatment cycle ] [ Designated as safety issue: No ]
    ET is the procedure in which one or more embryos are placed in the uterus. The number of embryos transferred, per participant, is summarized.

  • Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 1 [ Time Frame: At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 2 [ Time Frame: At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number of Participants by Category of Number of Good Quality Embryos Transferred in Treatment Cycle 3 [ Time Frame: At ET, Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    The number of embryos transferred, for each participant, by category of number of "good quality" embryos transferred, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 1 [ Time Frame: Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 2 [ Time Frame: Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Number and Quality of Embryos Obtained That Were Frozen in Treatment Cycle 3 [ Time Frame: Day 3 or Day 5 after oocyte pick-up (34-36 hours after [rec]hCG administration [approximately Stimulation Day 10]), in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    The number of embryos that were cryopreserved (frozen) for possible later use, for each participant, overall and by embryo quality categories, is summarized. Quality was rated as Grade 1, 2 or 3, or "other grade", with Grade 1 representing the best quality. The 2 highest quality grades (Grade 1 + 2) were combined into a summary category of "good quality."

  • Implantation Rate for Participants With ET [ Time Frame: Approximately 5-6 weeks after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    The implantation rate (in percent) is defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan after ET divided by the number of embryos transferred per participant.

  • Number of Participants With Biochemical Pregnancy, Clinical Pregnancy, Vital Pregnancy and Ongoing Pregnancy in Any of Treatment Cycles 1, 2 or 3 [ Time Frame: ≥14 days (for biochemical pregnancy), 5-6 weeks (for clinical pregnancy), 5-6 weeks to 10 weeks (for vital pregnancy) and 10 weeks up to 9 months (for ongoing pregnancy) after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    Biochemical pregnancy: Pregnancy proven by a biochemical pregnancy test using urine samples or serum samples collected at least 14 days after ET. Participants not having a positive biochemical pregnancy test result, but with an ultrasound scan showing at least one gestational sac were counted as having a biochemical pregnancy. Clinical pregnancy: Presence of at least one gestational sac as assessed by ultrasound scan. Vital pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

  • Number of Participants With Singleton and Multiple Ongoing Pregnancy in Any of Treatment Cycles 1, 2 or 3 [ Time Frame: 10 weeks up to 9 months after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    Singleton pregnancy is a pregnancy in which one fetus develops in the uterus. Multiple pregnancy is a pregnancy in which more than one fetus develops simultaneously in the uterus. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

  • Number of Participants With Miscarriage Among Participants With Clinical Pregnancy in Any of Treatment Cycles 1, 2 or 3 [ Time Frame: 5-6 weeks up to 9 months after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    Miscarriage: Loss of the fetus without induction or instrumentation, also known as "spontaneous abortion." Clinical pregnancy: Presence of at least one gestational sac as assessed by ultrasound scan.

  • Number of Participants With Miscarriage Among Participants With Vital Pregnancy in Any of Treatment Cycles 1, 2 or 3 [ Time Frame: 5-6 weeks up to 9 months after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    Miscarriage: Loss of the fetus without induction or instrumentation, also known as "spontaneous abortion." Vital pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan.

  • Number of Participants With Ectopic Pregnancy Among Participants With Biochemical Pregnancy in Any of Treatment Cycles 1, 2 or 3 [ Time Frame: From 2 weeks up to approximately 5-6 weeks after ET, within a treatment cycle ] [ Designated as safety issue: No ]
    Ectopic pregnancy: A pregnancy in which the embryo attaches itself in a place other than inside the uterus. The most common site for an ectopic pregnancy is within one of the two fallopian tubes. Biochemical pregnancy: Pregnancy proven by a biochemical pregnancy test using urine samples or serum samples collected at least 14 days after ET. Participants not having a positive biochemical pregnancy test result, but with an ultrasound scan showing at least one gestational sac were counted as having a biochemical pregnancy.

  • Number of Participants With Ongoing Pregnancy in Any FTET Cycle [ Time Frame: 10 weeks up to 9 months after ET within an FTET cycle ] [ Designated as safety issue: No ]
    After the first and after the second treatment cycle (i.e., a cycle in which corifollitropin alfa was administered for ovarian stimulation), participants could continue with a maximum of three FTET cycles before starting the following treatment cycle. This measure summarizes the number of participants with ongoing pregnancy following ET within an FTET cycle. Ongoing pregnancy: Presence of at least one fetus with heart activity as assessed by ultrasound scan at least 10 weeks after ET, or confirmed by live birth.

  • Cumulative Ongoing Pregnancy Rate: Percentage of Participants With Ongoing Pregnancy in Treatment Cycles 1, 2 or 3, or in Any FTET Cycle, or Who Had Ongoing Pregnancy That Was a Spontaneous Pregnancy [ Time Frame: Up to approximately 26 months after first dose of corifollitropin alfa ] [ Designated as safety issue: No ]
    The ongoing pregnancy rate, cumulative over the entire study (in percent), is defined as 100 times the number of participants who had an ongoing pregnancy in Treatment Cycles 1, 2 or 3, or in any FTET cycle, or who had a spontaneous ongoing pregnancy, divided by the total number of participants who were administered corifollitropin alfa in the study. A participant could only be represented once in the count of ongoing pregnancies for determination of cumulative ongoing pregnancy rate. After the first and after the second treatment cycle (i.e., a cycle in which corifollitropin alfa was administered for ovarian stimulation), participants could continue with a maximum of three FTET cycles before starting the following treatment cycle. A spontaneous pregnancy is a pregnancy that was not considered to have resulted from ET in a treatment cycle or FTET cycle.

  • Serum Follicle Stimulating Hormone (FSH) Levels in Treatment Cycle 1 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum FSH Levels in Treatment Cycle 2 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum FSH Levels in Treatment Cycle 3 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum FSH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Luteinizing Hormone (LH) Levels in Treatment Cycle 1 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum LH Levels in Treatment Cycle 2 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum LH Levels in Treatment Cycle 3 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum LH were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Estradiol Levels in Treatment Cycle 1 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Estradiol Levels in Treatment Cycle 2 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Estradiol Levels in Treatment Cycle 3 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum estradiol were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Progesterone Levels in Treatment Cycle 1 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Progesterone Levels in Treatment Cycle 2 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Progesterone Levels in Treatment Cycle 3 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum progesterone were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Inhibin-B Levels in Treatment Cycle 1 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 1 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Inhibin-B Levels in Treatment Cycle 2 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 2 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.

  • Serum Inhibin-B Levels in Treatment Cycle 3 [ Time Frame: Pre-dose (Stimulation Day 1) through 2 weeks after ET in Treatment Cycle 3 ] [ Designated as safety issue: No ]
    Blood samples for assessment of serum inhibin-B were taken pre-dose (Stimulation Day 1), Stimulation Day 5 or 6 (prior to first GnRH antagonist administration), Stimulation Day 8, day of (rec)hCG administration, day of ET and 2 weeks after ET.


Enrollment: 682
Study Start Date: September 2006
Study Completion Date: May 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Corifollitropin alfa 150 µg
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
Corifollitropin alfa 150 µg administered as a single subcutaneous dose.
Other Names:
  • Org 36286
  • SCH 900962
  • MK-8962
Biological: FSH
FSH administerd subcutaneously at a dose not to exceed 225 IU/day.
Biological: GnRH antagonist
GnRH antagonist administered subcutaneously at a dose of 0.25 mg/day.
Biological: (rec)hCG
(rec)hCG administered subcutaneously at a dose of 5,000-10,000 IU/250 µg.
Drug: Progesterone
Progesterone administered vaginally at a dose of at least 600 mg/day.

Detailed Description:

This trial is designed as an open-label, uncontrolled, repeated cycle trial to assess the non-immunogenicity and safety of corifollitropin alfa in participants undergoing repeated COS cycles for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) using a multiple dose GnRH antagonist protocol. The trial period per participant will cover 1, 2 or 3 COS treatment cycles and no more than three (in-between two stimulation cycles) Frozen-Thawed Embryo Transfer (FTET) cycles following either or both of the first two treatment cycles. In each stimulation cycle, participants receive a single injection of corifollitropin alfa and one week later, treatment is continued with a daily dose of any FSH-containing preparation up to the day of (rec)hCG administration for final oocyte maturation. Assessment of anti-corifollitropin alfa antibodies and local tolerance after corifollitropin alfa injection are important safety endpoints in this trial.

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • Use of hormonal preparations within 1 month prior to screening;
  • Administration of investigational drugs within three months prior to signing informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696878

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00696878     History of Changes
Other Study ID Numbers: P05714, MK-8962-007, 38825, 2004-004966-34
Study First Received: June 11, 2008
Results First Received: April 6, 2015
Last Updated: April 6, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: National Health Surveillance Agency
Chile: Instituto de Salud Pública de Chile
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: German Institute of Medical Documentation and Information
Hungary: National Institute of Pharmacy
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency
United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Infertility
Pharmacological effects of drugs
Hormones, Hormone Substitutes and Hormone Antagonists
Pharmacological Actions
Multi-center

Additional relevant MeSH terms:
Progesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Progestins

ClinicalTrials.gov processed this record on May 25, 2015