A Phase III, Randomized, Double-blind, Active-controlled, Equivalence Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of 100 µg Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation (COS) Using Daily Recombinant FSH (recFSH) as a Reference
Overview
- Phase
- Phase 3
- Intervention
- corifollitropin alfa (Org 36286)
- Conditions
- Infertility
- Sponsor
- Organon and Co
- Enrollment
- 397
- Primary Endpoint
- Number of Cumulus-oocyte-complexes Retrieved, Per Attempt
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
This is a randomized, double-blind, active-controlled, equivalence clinical trial investigating the efficacy and safety of a new treatment regimen with Org 36286, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in COS for Assisted Reproductive Technology (ART). For this regimen, patients receive a single injection of Org 36286 and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group patients receive daily injections of recFSH up to the day of triggering final oocyte maturation. Equivalence between the two treatment groups in the number of oocytes retrieved is the primary objective of this trial.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •History of/or any current (treated) endocrine abnormality;
- •History of ovarian hyper-response or ovarian hyperstimulation syndrome
- •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;
Arms & Interventions
corifollitropin alfa 100 µg
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.
Intervention: corifollitropin alfa (Org 36286)
corifollitropin alfa 100 µg
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.
Intervention: gonadatropin releasing hormone (GnRH) antagonist (ganirelix)
corifollitropin alfa 100 µg
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.
Intervention: human chorion gonadatropin (hCG)
corifollitropin alfa 100 µg
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.
Intervention: progesterone
corifollitropin alfa 100 µg
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.
Intervention: placebo-recFSH (follitropin alfa)
corifollitropin alfa 100 µg
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.
Intervention: open-label recFSH
recFSH 150 IU
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.
Intervention: recFSH (follitropin beta)
recFSH 150 IU
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.
Intervention: gonadatropin releasing hormone (GnRH) antagonist (ganirelix)
recFSH 150 IU
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.
Intervention: human chorion gonadatropin (hCG)
recFSH 150 IU
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.
Intervention: progesterone
recFSH 150 IU
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.
Intervention: placebo-corifollitropin alfa
recFSH 150 IU
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.
Intervention: open-label recFSH
Outcomes
Primary Outcomes
Number of Cumulus-oocyte-complexes Retrieved, Per Attempt
Time Frame: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
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.
Secondary Outcomes
- 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))
- Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)(Predose up to 2 weeks after ET (up to maximum of 6 weeks))
- Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)(Predose up to 2 weeks after ET (up to maximum of 6 weeks))
- Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection)(Predose up to 2 weeks after ET (up to maximum of 6 weeks))
- Serum Inhibin-B Levels (Restricted to Participants With hCG Injection)(Predose up to 2 weeks after ET (up to maximum of 6 weeks))
- Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration(Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration))
- Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only)(Up to 36 hours after administration of hCG)
- Fertilization Rate(Up to 10 weeks after ET)
- Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI)(Post fertilization Day 3 (up to a maximum of 2 days after hCG administration))
- Implantation Rate for Participants With ET(Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks))
- Number of Participants With Miscarriages(Up to 10 weeks after ET (up to a maximum of 14 weeks))
- Number of Participants With Pregnancies(Up to 10 weeks after ET (up to a maximum of 14 weeks))