Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as corifollitropin alfa (Org 36286), MK-8962, Elonva, Org 36286, SCH 900962, Org 36286 (corifollitropin alfa)
corifollitropin alfa · 11 trials · 5 indications
Participants underwent testicular ultrasound of left and right testes at pre-specified time points to measure TV. TV was measured as the sum of volumes of left and right testes. The linear mixed model with a fixed effect for baseline and Week 64 and a random effect for participant was used to calculate the mean change in log-transformed TV and associated 95% confidence intervals (CIs) from baseline to Week 64. The geometric mean ratio and its 95% CIs for TV were obtained by exponentiation. The ratio \> 1 indicated an increase in TV from baseline.
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was reported.
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE was reported.
Blood samples were collected at pre-specified time points to assess anti-CFA antibodies. The percentage of participants with anti-CFA antibodies after administration of CFA were reported.
Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.
Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.
The cumulative vital pregnancy rate was defined as the number of participants with at least 1 vital pregnancy in a controlled ovarian stimulation (COS) cycle in Base Study P06029 or a frozen-thawed embryo transfer (FTET) in Follow Up Study P06031, divided by the total number of participants in each Full Analysis Set (FAS) treatment group. A vital pregnancy was defined as an intrauterine pregnancy with fetal heart tones assessed at least 35 days (≥5 weeks) after embryo transfer (ET).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Corifollitropin alfa (CFA)+human Chorionic Gonadotropin (hCG) | EXPERIMENTAL | Participants received 100 μg (if body weight was ≤60 kg) or 150 μg (if body weight was \>60 kg) of CFA as a subcutaneous (SC) injection once every 2 weeks for 64 Weeks (Day 1, Week 0 through Week 64) and 500-5000 IU of hCG reconstituted with 1 ml of 0.9% sodium chloride solution, as a SC injection twice a week for 52 weeks (last day of Week 12 through Week 64). The total treatment duration was 64 Weeks. |
| Corifollitropin alfa 150 μg + hCG | EXPERIMENTAL | During a 16-week pretreatment phase, participants will receive twice-weekly subcutaneous (SC) injections of hCG 1500 or 3000 international units (IU). Eligible participants will then be enrolled in the combined treatment phase in which they will receive a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants will continue to receive twice-weekly hCG injections on the same schedule as the pretreatment phase. |
| Corifollitropin alfa 150 μg | EXPERIMENTAL | Participants in Base Study P06029 received a single injection of 150 ug corifollitropin alfa on Stimulation Day 1 and daily injections of placebo-recFSH from Stimulation Days 1 through 7. No medication or investigational product was administered in Follow-Up Study P06031. |
| recFSH 300 IU | ACTIVE_COMPARATOR | Participants in the reference group in Base Study P06029 received a single injection of placebo for corifollitropin alfa on Stimulation Day 1 and daily injections of 300 IU recFSH on Stimulation Days 1 through 7. No medication or investigational product was administered in Follow-Up Study P06031. |
| 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. |
| 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. |
| 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. |
| 150 µg Corifollitropin Alfa | EXPERIMENTAL | Participants 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_COMPARATOR | Participants 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. |
| Arm 1 | EXPERIMENTAL | 150 µg Org 36286 (corifollitropin alfa) |
| Arm 2 | EXPERIMENTAL | 100 µg Org 36286 (corifollitropin alfa) |
| 1 | EXPERIMENTAL | 60 µg Org 36286 (corifollitropin alfa) |
| 2 | EXPERIMENTAL | 120 µg Org 36286 (corifollitropin alfa) |
| 3 | EXPERIMENTAL | 180 µg Org 36286 (corifollitropin alfa) |
| 4 | ACTIVE_COMPARATOR | Follitropin beta injection |
| Org 36286 7.5 µg | EXPERIMENTAL | Org 36286 7.5 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. |
| Org 36286 15 µg | EXPERIMENTAL | Org 36286 15 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. |
| Org 36286 30 µg | EXPERIMENTAL | Org 36286 30 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. |
| Org 36286 60 µg | EXPERIMENTAL | Org 36286 60 µg administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. |
| Placebo | PLACEBO_COMPARATOR | Placebo to Org 36286 administered as a single subcutaneous injection on the day of the onset of a spontaneous or progestagen induced withdrawal bleeding or one to two days later. |
| Org 36286 120 μg + Puregon® 150 IU | EXPERIMENTAL | On Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 120 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm. |
| Org 36286 180 μg + Puregon® 150 IU | EXPERIMENTAL | Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 180 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm. |
| Org 36286 240 μg + Puregon® 150 IU | EXPERIMENTAL | Cycle Day 2 or Day 3, a single intra-abdominal injection of Org 36286 240 μg was administered to participants. On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm. |
| Puregon® 150 IU | ACTIVE_COMPARATOR | On stimulation Day 8, a daily subcutaneous dose of Puregon® 150 IU was administered up to and including the time of Pregnyl® administration as a single dose of 10,000 IU subcutaneously. The maximum treatment duration of Puregon® 150 IU was 19 days. Orgalutran® 0.25 mg was administered subcutaneously once daily up to and including the day of Pregnyl®, when the leading follicle reached a size of \>= 14 mm. |
| Org 36286 15 μg + Lyndiol® | EXPERIMENTAL | After a pill-free period of 7 days, participants took 1 oral tablet of Lyndiol® (50 μg ethinylestradiol + 2.5 mg lynestrenol) daily for a total period of at least 6 weeks to suppress endogenous gonadotropin secretion. After 3 weeks of Lyndiol® intake, participants received a single subcutaneous dose of Org 36286 15 μg. |
| Org 36286 30 μg + Lyndiol® | EXPERIMENTAL | After a pill-free period of 7 days, participants took 1 oral tablet of Lyndiol® (50 μg ethinylestradiol + 2.5 mg lynestrenol) daily for a total period of at least 6 weeks to suppress endogenous gonadotropin secretion. After 3 weeks of Lyndiol® intake, participants received a single subcutaneous dose of Org 36286 30 μg. |
| Org 36286 60 μg + Lyndiol® | EXPERIMENTAL | After a pill-free period of 7 days, participants took 1 oral tablet of Lyndiol® (50 μg ethinylestradiol + 2.5 mg lynestrenol) daily for a total period of at least 6 weeks to suppress endogenous gonadotropin secretion. After 3 weeks of Lyndiol® intake, participants received a single subcutaneous dose of Org 36286 60 μg. |
| Org 36286 120 μg + Lyndiol® | EXPERIMENTAL | After a pill-free period of 7 days, participants took 1 oral tablet of Lyndiol® (50 μg ethinylestradiol + 2.5 mg lynestrenol) daily for a total period of at least 6 weeks to suppress endogenous gonadotropin secretion. After 3 weeks of Lyndiol® intake, participants received a single subcutaneous dose of Org 36286 120 μg. |
| Name | Type | Description |
|---|---|---|
| Corifollitropin alfa | DRUG | CFA administered 100 μg (if body weight ≤60 kg) or 150 μg (if body weight \>60 kg) by SC injection, once every 2 weeks for 64 weeks (Day 1, Week 0 through Week 64). |
| hCG | DRUG | hCG 500-5000 IU reconstituted with 1 ml of 0.9% sodium chloride solution, as a SC injection twice a week for 52 weeks (last day of Week 12 through Week 64). |
| recFSH (follitropin beta) | BIOLOGICAL | Daily recFSH 300 IU administered under protocol P06029. |
| corifollitropin alfa (Org 36286) | DRUG | 100 µg corifollitropin alfa subcutaneous (SC) injection |
| gonadatropin releasing hormone (GnRH) antagonist (ganirelix) | DRUG | GnRH antagonist (ganirelix) administered SC at a dose of 0.25 mg/day |
| human chorion gonadatropin (hCG) | DRUG | hCG 5,000 IU or 10,000 IU administered SC |
| 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. |
| placebo-recFSH (follitropin alfa) | DRUG | Placebo-recFSH administered at the equivalent volume of 150 IU/day. |
| placebo-corifollitropin alfa | DRUG | Single SC injection of placebo-corifollitropin alfa administered on Day 2 or 3 of the menstrual cycle. |
| open-label recFSH | BIOLOGICAL | Open-label recFSH administered up to a maximum dose of 200 IU/day. |
| FSH | BIOLOGICAL | FSH administerd subcutaneously at a dose not to exceed 225 IU/day. |
| GnRH antagonist | BIOLOGICAL | GnRH antagonist administered subcutaneously at a dose of 0.25 mg/day. |
| (rec)hCG | BIOLOGICAL | (rec)hCG administered subcutaneously at a dose of 5,000-10,000 IU/250 µg. |
| RecFSH / Follitropin beta (Days 1 to 7) | BIOLOGICAL | Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7. |
| Placebo Corifollitropin alfa | DRUG | 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. |
| Placebo RecFSH / follitropin beta | DRUG | 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. |
| RecFSH / Follitropin beta (Days 8 to hCG) | BIOLOGICAL | From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG. |
| Ganirelix | DRUG | On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG |
| Org 36286 (corifollitropin alfa) | DRUG | A single dose of Org 36286 will be administered after down-regulation has been confirmed (E2 below 50 ng/L and P below 1.48 μg/L). The first group comprising subjects weighing \>= 50 kg will receive a dose of 150 μg Org 36286 (150 μg dose group). The second group comprising subjects weighing \<= 60 kg will receive a dose of 100 μg Org 36286 (100 μg dose group). |
| Follitropin beta injection | DRUG | Starting on Cycle Day 2, a fixed daily dose of 150 IU Puregon® SC was administered for the entire stimulation period up to and including the Day of hCG. Orgalutran® (0.25 mg) was administered once daily SC starting on Treatment Day 5 and given up to and including the day of hCG. The maximum total treatment duration was 19 days. |
| Org 36286 | DRUG | Org 36286 single-dose subcutaneous injection |
| Placebo | DRUG | Placebo to Org 36286 as a single-dose subcutaneous injection |
| Puregon® | DRUG | Subcutaneous Puregon® 150 IU |
| Orgalutran® | DRUG | Subcutaneous Orgalutran® 0.25 mg |
| Pregnyl® | DRUG | Subcutaneous Pregnyl® 10,000 IU |
| Lyndiol® | DRUG | Lyndiol® (50 μg ethinylestradiol + 2.5 mg lynestrenol) tablets orally once a day for 6 weeks. |
Inclusion Criteria: * Have legal representative who understands the study procedures, alternative treatments available and risks involved with the study, and voluntarily agrees to the individual's participation by giving written informed consent, and the individual has an age-appropriate understand...
Corifollitropin alfa is used for ovarian stimulation in infertility treatment, including in vitro fertilization, and for hypogonadotropic hypogonadism in males. It is also studied in fertilization and hypogonadism. It is given as a single injection to stimulate follicle growth in women undergoing assisted reproduction, and in combination with human chorionic gonadotropin in men with hypogonadotropic hypogonadism.
Corifollitropin alfa targets the follicle-stimulating hormone receptor (FSHR) as an agonist. By binding to and activating FSHR, it stimulates ovarian follicle growth in women and supports spermatogenesis in men with hypogonadotropic hypogonadism. This mechanism allows it to act as a long-acting follicle-stimulating hormone analog.
Corifollitropin alfa is developed by Organon & Co., which trades under the ticker OGN. Organon is the company responsible for its clinical development and potential commercialization.
Corifollitropin alfa is in Phase 2 of clinical development. It is an investigational drug and has not been approved by the FDA. The Phase 2 designation reflects ongoing research, though some trials have been completed.
Corifollitropin alfa has been studied in completed trials including NCT03019575 and NCT01709331 in adolescent and adult males with hypogonadotropic hypogonadism, and NCT01146418 and NCT00702845 in female infertility. These trials evaluated efficacy and safety in ovarian stimulation and hormone replacement settings.
Yes, corifollitropin alfa is also known as Org 36286. Both names refer to the same drug candidate developed by Organon & Co. for fertility and hypogonadism indications.