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

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Follitropin Epsilon; Drug: Follitropin Alfa

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Glycotope Investigational Site
  • Berlin, Germany, 14050
    • Glycotope Investigational Site
  • Bielefeld, Germany, 33619
    • Glycotope Investigational Medical Director
  • Düsseldorf, Germany, 40219
    • Glycotope Investigational Site
  • Heidelberg, Germany, 69115
    • Glycotope Investigational Site
  • Lübeck, Germany, 23538
    • Glycotope Investigational Site
• Hungary
  • Budapest, Hungary, 1125
    • Glycotope Investigational Site
  • Tapolca, Hungary, 8300
    • Glycotope Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Glycotope GmbH
• Investigators: Study Director: Study Director, Glycotope GmbH

Publications and helpful links

General Publications

• Griesinger G, Dietrich B, Stöckl 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 30, 2013

Study Registration Dates

• First Submitted: January 23, 2013
• First Submitted That Met QC Criteria: February 15, 2013
• First Posted (Estimate): February 18, 2013

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: in-vitro fertilization; reproductive disorder
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: GEXGP24201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No