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

Study Overview
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Brief Summary
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The aim of the current study was the determination of the recommended standard treatment dose of FSH-GEX(TM) in women undergoing intracytoplasmic sperm injection (ICSI) treatment as assessed by follicle growth.

Detailed Description
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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.

Official Title
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A Phase II, Multicentre, Multinational, Randomised, Assessor-Blind Trial to Investigate the Efficacy and Safety of Various Dosages of FSH-GEX™ in Comparison With 150 IU Gonal-f® in Women Undergoing ICSI Treatment

Conditions
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Infertility

Intervention / Treatment
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* Drug: Follitropin Epsilon
* Drug: Follitropin Alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment 1<br>Follitropin Epsilon 52.5 IU quaque die (QD) s.c. | Drug: Follitropin Epsilon<br> <br> * Other names: FSH-GEX(TM);|
| Experimental: treatment 2<br>Follitropin Epsilon 75 IU QD s.c. | Drug: Follitropin Epsilon<br> <br> * Other names: FSH-GEX(TM);|
| Experimental: treatment 3<br>Follitropin Epsilon 112.5 IU QD s.c. | Drug: Follitropin Epsilon<br> <br> * Other names: FSH-GEX(TM);|
| Experimental: treatment 4<br>Follitropin Epsilon 150 IU QD s.c. | Drug: Follitropin Epsilon<br> <br> * Other names: FSH-GEX(TM);|
| Experimental: treatment 5<br>Follitropin Epsilon 150 IU quaque altera die (QAD) s.c. | Drug: Follitropin Epsilon<br> <br> * Other names: FSH-GEX(TM);|
| Active Comparator: treatment 6<br>Follitropin alfa 150 IU QD s.c. | Drug: Follitropin Alfa<br> <br> * Other names: Gonal-f(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of follicles | 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) | day of hCG injection; variable timeframe; up to 18 days for maximum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Follicular response | 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 | every second day up to hCG injection; variable timeframe; up to 18 days for maximum | 
| Cumulus-oocyte-complexes | Number of retrieved cumulus-oocyte-complexes | at oocyte retrieval; 32 - 36 hours after hCG injection | 
| Oocytes retrieved | Number of oocytes retrieved (metaphase II) | at oocyte retrieval; 32 - 36 hours after hCG injection | 
| Two pronuclei oocytes | Number of two pronuclei (2PN) oocytes one day after follicle puncture | one day after oocyte retrieval | 
| Biochemical pregnancy rate | Based on positive β-hCG pregnancy test | 14 to 20 days after oocyte retrieval | 
| Clinical pregnancy rate | Based on clinical or ultrasound parameters (gestational sac, foetal heart beat | approx. 4 to 6 weeks after last FSH dose | 
| Implantation rate | Number of foetal sacs on sonography divided by number of embryos transferred per embryo transfer | approx. 4 to 6 weeks after last FSH dose | 
| Estradiol and inhibin B serum levels | Concentration of Estradiol and Inhibin B in Serum after FSH stimulation | every second day up to hCG injection; variable timeframe; up to 18 days maximum | 
| Adverse events, ovarian hyperstimulation syndrome, anti-drug-antibodies, overall tolerability | Incidence of adverse events, ovarian hyperstimulation syndrome, anti-drug-antibodies, overall tolerability | up to 4 to 6 weeks after last FSH dose | 
| Number of doses and total dose of FSH | The total dose is the amount of FSH-GEX(TM) or Gonal-f® administered to each patient during the stimulation period | variable timeframe; up to 18 days for maximum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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in-vitro fertilization, reproductive disorder