Efficacy and Safety of FSH-GEX™ in Comparison With 150 IU Gonal-f®

This was a phase II, randomized, assessor-blind, comparator-controlled, multiple dose study in women undergoing ICSI treatment.

The primary objective of the study was the determination of the recommended standard treatment dose of FSH-GEX™ as assessed by follicle growth dynamics in women between 18 and 37 years of age who were undergoing intracytoplasmic sperm injection treatment.

• Follitropin Epsilon (Drug), also known as FSH-GEX(TM)
• Follitropin Alfa (Drug), also known as Gonal-f(R)

Primary outcomes

• Number of follicles [day of hCG injection; variable timeframe; up to 18 days for maximum]: The number of follicles with a diameter of ≥ 12 mm on the day of human chorionic gonadotropin (hCG) injection after stimulation with follicle stimulating hormone (FSH)

Secondary outcomes

• Follicular response [every second day up to hCG injection; variable timeframe; up to 18 days for maximum]: For each ovary the number of follicles were classified and summarised as follows: mean diameter 8.0 - 9.9 mm, 10.0 - 11.9 mm, 12.0 - 13.9 mm, 14.0 - 15.9 mm, 16.0 - 17.9 mm, 18.0 - 19.9 mm, and >19.9 mm as determined by transvaginal ultrasonography
• Cumulus-oocyte-complexes [at oocyte retrieval; 32 - 36 hours after hCG injection]: Number of retrieved cumulus-oocyte-complexes
• Oocytes retrieved [at oocyte retrieval; 32 - 36 hours after hCG injection]: Number of oocytes retrieved (metaphase II)
• Two pronuclei oocytes [one day after oocyte retrieval]: Number of two pronuclei (2PN) oocytes one day after follicle puncture
• Biochemical pregnancy rate [14 to 20 days after oocyte retrieval]: Based on positive β-hCG pregnancy test
• Clinical pregnancy rate [approx. 4 to 6 weeks after last FSH dose]: Based on clinical or ultrasound parameters (gestational sac, foetal heart beat
• Implantation rate [approx. 4 to 6 weeks after last FSH dose]: Number of foetal sacs on sonography divided by number of embryos transferred per embryo transfer
• Estradiol and inhibin B serum levels [every second day up to hCG injection; variable timeframe; up to 18 days maximum]: Concentration of Estradiol and Inhibin B in Serum after FSH stimulation
• Adverse events, ovarian hyperstimulation syndrome, anti-drug-antibodies, overall tolerability [up to 4 to 6 weeks after last FSH dose]: Incidence of adverse events, ovarian hyperstimulation syndrome, anti-drug-antibodies, overall tolerability
• Number of doses and total dose of FSH [variable timeframe; up to 18 days for maximum]: The total dose is the amount of FSH-GEX(TM) or Gonal-f® administered to each patient during the stimulation period

Other outcomes

• Ongoing pregnancy rate [10 weeks after gestation]: A pregnancy is considered an ongoing pregnancy if pregnancy can be confirmed for more than 10 weeks after gestation.
• Life birth rate [up to nine month after embryo transfer]: The live birth rate will be calculated as the total number of live births divided by the number of randomised patients

Sex: Female, ages: 18 Years to 37 Years

Inclusion Criteria:

* Female patient for whom ICSI treatment is justified
* Serum follicle-stimulating hormone concentration
* Anti-mullerian hormone concentration
* Antral follicle count
* Body mass index and body weight
* Presence of both ovaries
* Regular spontaneous cycles between 21 and 35 days in length
* Normal uterine cavity as assessed by transvaginal sonography at Screening
* Willing and able to comply with the protocol
* Willing and able to provide written informed consent

Exclusion Criteria:

* Patients who had more than two unsuccessful previous assisted reproduction technology cycles before inclusion into the study
* Previous poor responders
* Patients with previous hyperstimulation syndrome or cycle cancellation because of imminent hyperstimulation syndrome
* Patients with a history of or current polycystic ovarian morphology syndrome
* Patients with a history of or current endometriosis III or IV
* Presence of ovarian cyst at Screening
* Any contraindication to becoming pregnant
* History of ≥ 3 clinical or preclinical miscarriages
* Abnormal cervical smear, Papanicolaou \[PAP\] score ≥ 3
* Any history of malignant cancer other than in situ breast or skin cancer requiring local excision
* Any endocrine abnormalities requiring treatment
* Any clinically significant systematic disease
* Any known infection with human immunodeficiency virus, hepatitis B or C
* History of thrombosis or other risk factors including any coagulation abnormality leading to an increased risk of clotting
* Family history of genetic risk factors concerning pregnancy or birth
* Use of concomitant medication, which in the opinion of the investigator might interfere with ICSI preparation procedures
* Active smoking
* Any active substance abuse of drugs, medications or alcohol within the last five years
* Patients in an institution by official or court order
* Patients who are unable or unwilling to provide informed consent
* Any participation in another clinical trial within the last 60 days before randomisation
* Previous FSH-GEX™ administration.
* Known hypersensitivity to any component of the investigational and non investigational products used in this study

• Results publication: Griesinger G, Dietrich B, Stockl L, Eckert K, Goletz S, Tandler-Schneider A. Fully human glyco-optimized recombinant FSH (follitropin epsilon) - a randomized, comparator-controlled phase II clinical trial. Reprod Biomed Online. 2020 Feb;40(2):331-341. doi: 10.1016/j.rbmo.2019.09.003. Epub 2019 Sep 16. PMID 31982355

• Study Director, Study director, Glycotope GmbH