Ignite Creation Date:
2024-05-06 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 2:21 PM
Study NCT ID:
NCT05173597
Status:
RECRUITING
Last Update Posted:
2023-11-21
First Post:
2021-11-18
Brief Title:
Real-world Evidence on Follitropin Delta Individual Dosing
Sponsor:
University of Luebeck
Organization:
University of Luebeck
Study Overview
Official Title:
The Performance of an Individual Dosing Regimen of Follitropin Delta for Controlled Ovarian Stimulation for IVF in a Real-word Setting a Non-interventional Observational Study
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
As part of the in vitro fertilisation treatment ovarian stimulation is routinely performed For this purpose FSH preparations are used Follitropin delta is a FSH preparation that is approved for a wide range of applications and is dosed individually according to body weight and serum anti-Müllerian hormone AMH Body weight is used to estimate the distribution volume of the glycoprotein FD in the patient and is thus a proxy of exposure The AMH is used to estimate the ovarian reserve and thus the number of follicles in the ovaries that can be recruited by Follitropin delta stimulation An algorithm is used for individual dosing The aim of individual dosing is to reduce the probability of an under or overreaction of the ovaries to FSH therapy
In contrast to phase III registration studies patients with severe overweight and underweight as well as very high and very low AMH values and associated disorders of the menstrual cycle and oocyte maturation are also found in the reality of care The performance of the dosing algorithm and thus the results of ovarian stimulation in these subgroups of patients have so far been insufficiently investigated in the phase III registration trials
In the present study no statistical hypothesis will be tested The study is descriptive by design and the analyses are descriptive and exploratory NIS is chosen in order to explore how the individualized dosing regimen of REKOVELLE performs in routine clinical practice and to investigate the effectiveness and safety of REKOVELLE under real-world conditions This is a monocentric prospective non-interventional cohort study conducted in normal care setting in a fertility clinic that will collect information from 850 women undergoing up to two cycles of IVF or ICSI treatment with controlled ovarian stimulation with REKOVELLE
In contrast to phase III registration studies patients with severe overweight and underweight as well as very high and very low AMH values and associated disorders of the menstrual cycle and oocyte maturation are also found in the reality of care The performance of the dosing algorithm and thus the results of ovarian stimulation in these subgroups of patients have so far been insufficiently investigated in the phase III registration trials
In the present study no statistical hypothesis will be tested The study is descriptive by design and the analyses are descriptive and exploratory NIS is chosen in order to explore how the individualized dosing regimen of REKOVELLE performs in routine clinical practice and to investigate the effectiveness and safety of REKOVELLE under real-world conditions This is a monocentric prospective non-interventional cohort study conducted in normal care setting in a fertility clinic that will collect information from 850 women undergoing up to two cycles of IVF or ICSI treatment with controlled ovarian stimulation with REKOVELLE
Detailed Description:
Infertility is often defined as the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse Many factors age gynaecological problems life style factors can cause infertility and may involve the male the female or both
Global estimates suggest that the 12-month prevalence rate of infertility ranged from 35 to 167 in developed countries with a median prevalence of 9 worldwide for women aged 20 - 44 years A recent study estimated that 19 of child-seeking women aged 20 - 44 years experienced primary infertility unable to have a live birth and 105 secondary infertility at least one live birth The proportion of infertile couples seeking any infertility medical care ranges from 51 in less developed countries to 56 in developed countries and 22 actually received infertility treatment
Among fertility treatment controlled ovarian stimulation COS with recombinant or urinary follicle stimulating hormone FSH and human menotropin gonadotropin hMG aims to obtain an adequate number of competent oocytes to be used for assisted reproductive technologies ART such as an in vitro fertilisation IVF or intracytoplasmic sperm injection ICSI with minimum risks for the woman
The ovarian response is influenced by the dose of gonadotropin but there is a large variability across patients for the same dose of gonadotropin A standard starting dose of gonadotropin in women with a low ovarian reserve may result in a poor ovarian response In women with a high ovarian reserve the same dose may result in an excessive response and therefore increases the risk of complications such as the ovarian hyperstimulation syndrome OHSS OHSS is a rare but critical complication associated with gonadotropin use Severe OHSS occurs in approximately 14 of all COS cycles
Individualizing COS regimens is therefore crucial to ensure an appropriate dosing from the start of stimulation in order to reduce the risk of cycle cancellation due to poor response and minimize the iatrogenic risks due to an excessive responseThe use of biomarkers which can predict ovarian response to exogenous FSH stimulation has been extensively investigated Among the different biomarkers the serum level of anti-müllerian hormone AMH is currently considered as the most robust marker of the ovarian reserve In addition AMH serum levels shows relative stability and consistency during the menstrual cycle and can therefore be measured at any time of the menstrual cycle
In December 2016 Ferring received Marketing Authorisation approval from the European Commission for follitropin delta FE 999049 under the trade name REKOVELLE a new human recombinant FSH rFSH The indication is Controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies ART such as an in vitro fertilisation IVF or intracytoplasmic sperm injection ICSI cycle This is the first rFSH treatment to be administered with an individualised dosing regimen based on a womans serum AMH level as well as her body weight
This individualised dosing regimen was established in a phase-2 AMH-stratified trial conducted in 265 IVFICSI patients using pharmacokinetic PK and pharmacodynamic PD modelling and simulation A robust assay was developed in collaboration with Roche Diagnostics to ensure a reliable assessment of AMH levels at the standards intended for companion diagnostics
The efficacy and safety of Follitropin Delta was first evaluated in the ESTHER-1 Evidence- based Stimulation Trial with Human rFSH in Europe and Rest of World phase-3 trial which compared the individualized Follitropin Delta dosing based on AMH level and body weight with conventional Follitropin Alfa Gonal-F dosing Patients who did not achieve an ongoing pregnancy could continue in the ESTHER-2 phase-3 trial which evaluated the immunogenicity in repeated COS cycles The results of the phase-3 trials showed that individualized Follitropin Delta was non-inferior to conventional Follitropin Alfa for ongoing pregnancy and ongoing implantationrates Overall women treated with individualized Follitropin Delta dosing reached more frequently the prespecified optimum oocyte yield 8-14 oocytes with fewer cases of extreme ovarian responses and a reduced need for OHSS preventive measures
The phase III clinical program has demonstrated that REKOVELLE is an effective and well-tolerated treatment for controlled ovarian stimulation Nevertheless while clinical trials provide crucial information about drug efficacy and safety under controlled conditions in a selected group of patients broader information is needed to explore how the individualized dosing regimen of REKOVELLE is used in routine clinical practice and to investigate the effectiveness and safety of REKOVELLE under real-world conditions
Global estimates suggest that the 12-month prevalence rate of infertility ranged from 35 to 167 in developed countries with a median prevalence of 9 worldwide for women aged 20 - 44 years A recent study estimated that 19 of child-seeking women aged 20 - 44 years experienced primary infertility unable to have a live birth and 105 secondary infertility at least one live birth The proportion of infertile couples seeking any infertility medical care ranges from 51 in less developed countries to 56 in developed countries and 22 actually received infertility treatment
Among fertility treatment controlled ovarian stimulation COS with recombinant or urinary follicle stimulating hormone FSH and human menotropin gonadotropin hMG aims to obtain an adequate number of competent oocytes to be used for assisted reproductive technologies ART such as an in vitro fertilisation IVF or intracytoplasmic sperm injection ICSI with minimum risks for the woman
The ovarian response is influenced by the dose of gonadotropin but there is a large variability across patients for the same dose of gonadotropin A standard starting dose of gonadotropin in women with a low ovarian reserve may result in a poor ovarian response In women with a high ovarian reserve the same dose may result in an excessive response and therefore increases the risk of complications such as the ovarian hyperstimulation syndrome OHSS OHSS is a rare but critical complication associated with gonadotropin use Severe OHSS occurs in approximately 14 of all COS cycles
Individualizing COS regimens is therefore crucial to ensure an appropriate dosing from the start of stimulation in order to reduce the risk of cycle cancellation due to poor response and minimize the iatrogenic risks due to an excessive responseThe use of biomarkers which can predict ovarian response to exogenous FSH stimulation has been extensively investigated Among the different biomarkers the serum level of anti-müllerian hormone AMH is currently considered as the most robust marker of the ovarian reserve In addition AMH serum levels shows relative stability and consistency during the menstrual cycle and can therefore be measured at any time of the menstrual cycle
In December 2016 Ferring received Marketing Authorisation approval from the European Commission for follitropin delta FE 999049 under the trade name REKOVELLE a new human recombinant FSH rFSH The indication is Controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies ART such as an in vitro fertilisation IVF or intracytoplasmic sperm injection ICSI cycle This is the first rFSH treatment to be administered with an individualised dosing regimen based on a womans serum AMH level as well as her body weight
This individualised dosing regimen was established in a phase-2 AMH-stratified trial conducted in 265 IVFICSI patients using pharmacokinetic PK and pharmacodynamic PD modelling and simulation A robust assay was developed in collaboration with Roche Diagnostics to ensure a reliable assessment of AMH levels at the standards intended for companion diagnostics
The efficacy and safety of Follitropin Delta was first evaluated in the ESTHER-1 Evidence- based Stimulation Trial with Human rFSH in Europe and Rest of World phase-3 trial which compared the individualized Follitropin Delta dosing based on AMH level and body weight with conventional Follitropin Alfa Gonal-F dosing Patients who did not achieve an ongoing pregnancy could continue in the ESTHER-2 phase-3 trial which evaluated the immunogenicity in repeated COS cycles The results of the phase-3 trials showed that individualized Follitropin Delta was non-inferior to conventional Follitropin Alfa for ongoing pregnancy and ongoing implantationrates Overall women treated with individualized Follitropin Delta dosing reached more frequently the prespecified optimum oocyte yield 8-14 oocytes with fewer cases of extreme ovarian responses and a reduced need for OHSS preventive measures
The phase III clinical program has demonstrated that REKOVELLE is an effective and well-tolerated treatment for controlled ovarian stimulation Nevertheless while clinical trials provide crucial information about drug efficacy and safety under controlled conditions in a selected group of patients broader information is needed to explore how the individualized dosing regimen of REKOVELLE is used in routine clinical practice and to investigate the effectiveness and safety of REKOVELLE under real-world conditions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None