Recombinant FSH Investigation in the Treatment of Infertility With Assisted Reproductive Technology (ART) (RITA-1)
Study Details
Study Description
Brief Summary
This trial investigates the effects of FE 999049 compared to placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Follitropin delta
|
Drug: Follitropin delta
Follitropin delta
Other Names:
|
| Placebo Comparator: Placebo
|
Other: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Cumulative ongoing pregnancy rate after the fresh cycle and cryopreserved cycles initiated within 12 months from the start of controlled ovarian stimulation (COS) [8-9 weeks after transfer (up to approximately 16 months after start of stimulation)]
Secondary Outcome Measures
- Ongoing pregnancy rate in the fresh cycle and in the cryopreserved cycles [8-9 weeks after transfer (up to approximately 16 months after start of stimulation)]
- Time from start of controlled ovarian stimulation (COS) to ongoing pregnancy across the fresh and cryopreserved cycles [8-9 weeks after transfer (up to approximately 16 months after start of stimulation)]
- Ongoing implantation rate in the fresh cycle, the cryopreserved cycles and cumulatively [8-9 weeks after transfer (up to approximately 16 months after start of stimulation)]
- Clinical pregnancy rate in the fresh cycle, the cryopreserved cycles and cumulatively [5-6 weeks after transfer (up to approximately 15 months after start of stimulation)]
- Vital pregnancy rate in the fresh cycle, the cryopreserved cycles and cumulatively [5-6 weeks after transfer (up to approximately 15 months after start of stimulation)]
- Implantation rate in the fresh cycle, the cryopreserved cycles and cumulatively [5-6 weeks after transfer (up to approximately 15 months after start of stimulation)]
- Positive beta human chorionic gonadotropin (βhCG) rate in the fresh cycle, the cryopreserved cycles and cumulatively [10-14 days after transfer (up to approximately 14 months after start of stimulation)]
- Proportion of participants in the fresh cycle with triggering of final follicular maturation (with human chorionic gonadotropin [hCG], with gonadotropin-releasing hormone [GnRH] agonist, and in total), cycle cancellation and transfer cancellation [Up to 5 days after oocyte retrieval (up to 27 days after start of stimulation)]
- Number of follicles on stimulation day 5 [On stimulation day 5]
The total number of follicles and the number of follicles per size category will be reported
- Number of follicles at end-of-stimulation [At end-of-stimulation (up to 20 stimulation days)]
The total number of follicles and the number of follicles per size category will be reported
- Number of oocytes retrieved [On day of oocyte retrieval (up to 22 days after start of stimulation)]
- Proportion of participants with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved [On day of oocyte retrieval (up to 22 days after start of stimulation)]
- Number of metaphase II oocytes [On day of oocyte retrieval (up to 22 days after start of stimulation)]
- Number of fertilized oocytes and fertilization rate [On day 1 after oocyte retrieval (up to 23 days after start of stimulation)]
- Number of blastocysts on day 5 after oocyte retrieval [On day 5 after oocyte retrieval]
The number of blastocysts (total and good-quality) will be reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
- Endometrial thickness [On stimulation day 5 and at end-of-stimulation (up to 20 stimulation days)]
Mean endometrial thickness will be reported
- Echogenicity pattern [On stimulation day 5 and at end-of-stimulation (up to 20 stimulation days)]
The distribution of subjects with hypoechogenic, isoechogenic, or hyperechogenic endometrium will be reported
- Oocyte utilization rate [On day of oocyte retrieval upto 12 months after start of controlled ovarian stimulation (COS)]
- Oocyte efficiency index [8-9 weeks after transfer]
The oocyte efficiency index will be calculated based on the number of oocytes retrieved and the cumulative number of ongoing pregnancies
- Percentage of blastocysts surviving cryopreservation [0 hour (+0.5 hour) after thawing]
- Percentage of blastocysts with re-expansion after cryopreservation [2.5 hour (±0.5 hour) after thawing]
- Number of cryopreserved cycles initiated within 12 months from the start of controlled ovarian stimulation (COS), and number of cryopreserved cycles with blastocyst transfer [Up to 12 months after start of stimulation]
The total number of cryopreserved cycles initiated and the number of cryopreserved cycles with blastocyst transfer will be reported
- Circulating concentrations of anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, inhibin A and inhibin B [From screening to the day of oocyte retrieval (up to 22 days after start of stimulation)]
- Total gonadotropin dose [Up to 20 stimulation days]
- Number of stimulation days [Up to 20 stimulation days]
- Number of dose adjustments [Up to 20 stimulation days]
- Frequency and intensity of adverse events [From time of signing informed consent until the end-of-cycle visit in the fresh cycle (up to approximately 6 months)]
- Changes in circulating levels of clinical chemistry compared to baseline [From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)]
Measured by CHEM-20
- Changes in haematology parameters compared to baseline [From screening to the end-of-cycle visit in the fresh cycle (approximately 6 months)]
Measured by complete blood count (CBC)
- Frequency and intensity of injection site reactions (redness, pain, itching, swelling and bruising) assessed by the participant during the stimulation period [Up to 20 stimulation days]
- Proportion of participants with treatment-induced anti-FSH antibodies [Up to 28 days after end of the stimulation period]
- Frequency and intensity of immune-related adverse events [From time of signing informed consent until the end-of-cycle visit in the fresh cycle (approximately 6 months)]
- Proportion of participants with cycle cancellations due to an adverse event, including immune-related adverse events, or due to technical malfunctions of the administration pen [Up to 20 stimulation days]
- Proportion of participants with ovarian hyperstimulation syndrome (OHSS), overall and by grade, and proportion of participants with moderate/severe OHSS [≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation (late OHSS)]
- Proportion of participants hospitalized due to ovarian hyperstimulation syndrome (OHSS) and proportion of participants undergoing paracentesis due to OHSS [≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation (late OHSS)]
- Rate of multi-fetal gestation, biochemical pregnancy, spontaneous abortion, ectopic pregnancy (with and without medical/surgical intervention) and vanishing twins in the fresh cycle and in the cryopreserved cycles [Up to 8-9 weeks after transfer]
The percentage of subjects with each of these events will be reported.
- Technical malfunctions of the administration pen [Up to 20 stimulation days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Informed Consent Documents signed prior to any trial-related procedure.
-
In good physical and mental health in the judgement of the investigator.
-
Pre-menopausal females between the ages of 18 and 34 years. The subjects must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 34 years (up to the day before the 35th birthday) at the time of randomization.
-
Body mass index (BMI) between 17.5 and 38.0 kg/m2 (both inclusive) at screening.
-
Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor.
-
Documented history of infertility for at least 12 months before randomization (not applicable in case of tubal or severe male factor infertility, or when the use of donor sperm is indicated).
-
Regular menstrual cycles of 24-35 days (both inclusive).
-
Hysterosalpingography, hysteroscopy or saline infusion sonography, documenting a uterus consistent with expected normal function (e.g. no evidence of clinically interfering uterine fibroids defined as submucous fibroids of any size or intramural fibroids larger than 3 cm in diameter, no polyps and no congenital structural abnormalities which are associated with a reduced chance of pregnancy) at screening or within 1 year prior to screening.
-
Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of significant abnormality (e.g. enlarged ovaries which would contraindicate the use of gonadotropins) and normal adnexa (e.g. no hydrosalpinx) at screening. Both ovaries must be accessible for oocyte retrieval.
-
Early follicular phase (cycle day 2-4) serum levels of FSH between 1 and 15 IU/L (results obtained within 3 months prior to randomization).
-
Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests at screening or within 6 months prior to screening.
-
Willing to accept single blastocyst transfer in the fresh cycle and in the cryopreserved cycles initiated within 12 months from the start of COS using blastocysts obtained in this trial.
Exclusion Criteria:
-
More than one previous COS cycle for IVF/ICSI.
-
Known endometriosis stage III-IV (defined by the revised ASRM classification, 2012 ).
-
Known history of anovulation.
-
One or more follicles greater than or equal to 10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1.
-
Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy [excluding ectopic pregnancy] and before week 24 of pregnancy).
-
Known abnormal karyotype of subject or of her partner / sperm donor, as applicable, depending on source of sperm used for insemination in this trial. In case partner sperm will be used and the sperm production is severely impaired (concentration <1 million/mL), normal karyotype, including no Y-chromosome microdeletion, must be documented.
-
Any known clinically significant systemic disease (e.g. insulin-dependent diabetes).
-
Known inherited or acquired thrombophilia.
-
Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
-
Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of pharmacologically controlled sub-clinical hypothyroidism.
-
Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotropins.
-
Known moderate or severe impairment of renal or hepatic function.
-
Any abnormal finding of clinical chemistry, hematology, thyroid-stimulating hormone (TSH) or prolactin, or vital signs at screening, which is judged clinically significant by the investigator.
-
Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved).
-
Findings at the gynecological examination at screening which preclude gonadotropin stimulation or are associated with a reduced chance of pregnancy, e.g. congenital uterine abnormalities or retained intrauterine device.
-
Pregnancy (negative urinary pregnancy tests must be documented at screening and prior to randomization) or contraindication to pregnancy.
-
Known current active pelvic inflammatory disease.
-
Use of fertility modifiers during the last menstrual cycle before randomization, including dehydroepiandrosterone (DHEA), metformin or cycle programming with oral contraceptives, progestogen or estrogen preparations.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fertility Treatment Center | Tempe | Arizona | United States | 85284 |
| 2 | HRC Fertility | Encino | California | United States | 91436 |
| 3 | Center for Advanced Reproductive Services PC | Farmington | Connecticut | United States | 06032 |
| 4 | Reproductive Associates of Delaware | Newark | Delaware | United States | 19713 |
| 5 | Women's Medical Research Group, LLC | Clearwater | Florida | United States | 33759 |
| 6 | Center for Reproductive Medicine | Winter Park | Florida | United States | 32789 |
| 7 | Fertility Institute of Hawaii, INC | Honolulu | Hawaii | United States | 96814 |
| 8 | Fertility Centers of Illinois (RH) | Chicago | Illinois | United States | 60610 |
| 9 | InVia Fertility | Hoffman Estates | Illinois | United States | 60169 |
| 10 | Boston IVF | Waltham | Massachusetts | United States | 02451 |
| 11 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 12 | Reproductive Endocrinology Associates of Charlotte (REACH) S. Corporation | Charlotte | North Carolina | United States | 28207 |
| 13 | Carolina Conceptions | Raleigh | North Carolina | United States | 27607 |
| 14 | Institute for Reproductive Health | Cincinnati | Ohio | United States | 45209 |
| 15 | Abington Reproductive Medicine | Abington | Pennsylvania | United States | 19046 |
| 16 | Main Line Fertility Center | Bryn Mawr | Pennsylvania | United States | 19010 |
| 17 | Fertility Associates of Memphis, PLLC | Memphis | Tennessee | United States | 38120 |
| 18 | Center for Assisted Reproduction | Bedford | Texas | United States | 76022 |
| 19 | Houston Fertility Institute | Houston | Texas | United States | 77063 |
| 20 | Center of Reproductive Medicine | Webster | Texas | United States | 77598 |
| 21 | Utah Fertility Center | Pleasant Grove | Utah | United States | 84062 |
| 22 | Eastern Virginia Medical School | EVMS Obstetrics & Gynecology | Norfolk | Virginia | United States | 23507 |
| 23 | Seattle Reproductive Medicine WA | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Ferring Pharmaceuticals
Investigators
- Study Director: Global Clinical Compliance, Ferring Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 000001