(Follitropin alfa/Lutropin alfa) - 药物靶点：FSHR_在研适应症：促卵泡激素缺乏，促黄体激素缺乏_专利_临床

概要

基本信息

药物类型

激素

别名

Lutropin alfa/follitropin alfa、Pergoveris、Recombinant human follicle stimulating hormone/luteinising hormone

+ [4]

靶点

FSHR

作用机制

FSHR激动剂(卵泡刺激素受体激动剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

最高研发阶段批准上市

首次获批日期

欧盟 (2007-06-25),

促卵泡激素缺乏促黄体激素缺乏

最高研发阶段(中国)无进展

特殊审评-

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序列信息

Sequence Code 3246α

当前序列信息引自: *****

Sequence Code 3246

当前序列信息引自: *****

Sequence Code 83626α

当前序列信息引自: *****

Sequence Code 3253

当前序列信息引自: *****

关联

15

项与 Follitropin alfa/Lutropin alfa 相关的临床试验

NCT04899193 / Completed临床1期

A Phase I, Open-label, Randomized, Three-period, Crossover, Single-center Trial to Assess the Bioequivalence of the Co-administration of 900 IU of Follitropin Alfa (Gonal-f) and 450 IU of Lutropin Alfa (Luveris) Versus the Fixed Combination of 900 IU Follitropin Alfa and 450 IU Lutropin Alfa in Pergoveris, Administered SC as Liquid and FD Formulation, in Pituitary Suppressed Healthy Premenopausal Female Chinese Participants

The main purpose of this study is to assess the bioequivalence (BE) of the fixed combination of follitropin alfa and lutropin alfa in Pergoveris freeze-dried (FD) (Test 1) or in Pergoveris Liquid (Test 2) versus the co-administration of Gonal-f and Luveris (Reference), administered subcutaneously (SC) in pituitary suppressed, healthy premenopausal Chinese female participants, at the doses of 900 international unit (IU) of follitropin alfa and 450 IU lutropin alfa.

开始日期2021-05-08

申办/合作机构

Merck Healthcare KGaA

NCT04719000 / Recruiting临床4期IIT

PErsonalized Addition of Recombinant LH in Suboptimal Responders >35 Years Old (POSEIDON Group 2): A Randomized Controlled Trial

Different ovarian stimulation regimens have shown to modify late follicular phase hormonal profiles. Besides, recent studies confirm that progesterone levels and their variation in the last day of oocyte maturation are affected by the dose of gonadotropins administered and by other factors. Progesterone elevation in late follicular phase of in vitro fertilization/intracytoplasmatic sperm injection (IVF/ICSI) cycles under ovarian stimulation compromises implantation rates due to a negative effect on the endometrium. However, there is still conflict in the literature questioning whether progesterone levels alone on the triggering day is a sufficient indicator as progesterone does not give the full picture of the ovarian functions, number of follicles as well as estrogen production that facilitate endometrial growth, thus some studies suggest that especially in aged and poor responders Progesterone/Estrogen (P4/E2) ratio has a better reflection (Progesterone (ng/mL) ×1,000/estradiol(pg/mL)) on the ovarian function.
The scope of the current pilot study is to compare serum progesterone levels as well as P4/E2 ratio on the day of ovulation triggering of women belonging to POSEIDON category group 2 who undergo a new ovarian stimulation with a dose of rhFSH 300 IU or 300 IU rhFSH plus 150 IU recombinant human luteinizing hormone (rhLH) in a gonadotropin-releasing hormone (GnRH) antagonist protocol.

开始日期2021-02-04

申办/合作机构

Merck & Co., Inc.

NCT04385342 / Unknown status临床4期IIT

Follicle Stimulating Hormone (FSH) Followed by Human Menopausal Gonadotropin (HMG) Versus FSH Plus HMG During Controlled Ovarian Stimulation for in Vitro Fertilization

The aim of this study is to compare the clinical outcomes of sequential administration of FSH and HP-hMG FSH alone versus concomitant administration of FSH and HP-hMG during controlled ovarian stimulation in IVF cycles.

开始日期2020-06-30

申办/合作机构

Mansoura University

100 项与 Follitropin alfa/Lutropin alfa 相关的临床结果

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100 项与 Follitropin alfa/Lutropin alfa 相关的转化医学

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100 项与 Follitropin alfa/Lutropin alfa 相关的专利（医药）

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59

项与 Follitropin alfa/Lutropin alfa 相关的文献（医药）

2023-03-27·Diagnostics (Basel, Switzerland)

Corifolitropin-Alfa plus Five Days Letrozole Versus Daily Recombinant-FSH in Expected Normo-Responder Patients: A Retrospective Comparative Study.

Article

作者: Giuseppe D'Amato ; Anna Maria Caringella ; Antonio Stanziano ; Clementina Cantatore ; Antonio D'Amato ; Ettore Cicinelli ; Amerigo Vitagliano

Background: In recent times, different novel GnRH-antagonist protocols with various combinations of gonadotropins and other molecules (e.g., aromatase inhibitors, selective estrogen receptor modulators) have been proposed for expected normal ovarian responders undergoing assisted reproductive treatments. The purpose of this study was to evaluate the effectiveness of a novel ovarian stimulation protocol based on the combination of corifollitropin-alfa plus five days of letrozole in E-NOR women undergoing IVF as compared with a daily recombinant-FSH regimen. Methods: We conducted a retrospective-controlled study on 182 couples undergoing their first IVF attempt. In Group A (experimental), letrozole (2.5 mg daily) was administered from day 2 (up to day 6 of the cycle), followed by corifollitropin-alfa on day 3 and daily recombinant FSH from day 10. In Group B, recombinant FSH from day 2 were administered (150 IU-225 IU daily). Statistical analysis was completed using SPSS Statistics. The primary outcome was the total number of MII oocytes retrieved. Results: Group A showed similar results compared to Group B in terms of MII oocytes, live birth, implantation, and clinical pregnancy rates (p = ns). Nevertheless, the experimental group was associated with a trend towards a higher number of developing follicles, total oocytes, and embryos (p < 0.05) with lower estradiol and progesterone values at ovulation induction compared to Group B, resulting in an increased chance of performing a fresh embryo transfer (p < 0.05). Conclusions: The combination of CFα plus five days of letrozole was associated with a trend towards a higher number of developing follicles, total oocytes, and obtained embryos. Moreover, the experimental protocol resulted in lower estradiol and progesterone values at ovulation induction compared to daily rFSH, with an increased chance of performing a fresh embryo transfer (with no OHSS occurrence). Given the observational design of our study, further well-conducted RCTs are needed.

2021-10-01·Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen.

Article

作者: Amanda Souza Setti ; Daniela Paes de Almeida Ferreira Braga ; Assumpto Iaconelli ; Edson Borges

OBJECTIVE:

To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle.

METHODS:

For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups.

RESULTS:

Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group.

CONCLUSION:

Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

2021-04-16·Human reproduction (Oxford, England)1区 · 医学

A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome.

1区 · 医学

Article

作者: P Lehert ; P Arvis ; C Avril ; N Massin ; J Parinaud ; G Porcu ; C Rongières ; P Sagot ; R Wainer ; T D'Hooghe

STUDY QUESTION:

Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa?

SUMMARY ANSWER:

The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data.

WHAT IS KNOWN ALREADY:

Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO).

STUDY DESIGN, SIZE, DURATION:

The external validation of the PROsPeR score was completed using data derived from eight different centres in France. In addition, the follitropin alfa data from the ESPART RCT, originally used to develop the PROsPeR score, were used as reference cohort. The external validation of the PROsPeR score l was assessed using AUC. A predetermined non-inferiority limit of 0.10 compared with a reference sample and calibration (Hosmer-Lemeshow test) were the two conditions required for evaluation.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The observational cohort included data from 8085 ART treatment cycles performed with follitropin alfa in patients with POR defined according to the ESHRE Bologna criteria (17.6% of the initial data set). The ESPART cohort included 477 ART treatment cycles with ovarian stimulation performed with follitropin alfa in patients with POR.

MAIN RESULTS AND THE ROLE OF CHANCE:

The external validation of the PROsPeR score to identify subpopulations of women with POR with different live birth outcomes was shown in the observational cohort (AUC = 0.688; 95% CI: 0.662, 0.714) compared with the ESPART cohort (AUC = 0.695; 95% CI: 0.623, 0.767). The AUC difference was -0.0074 (95% CI: -0.083, 0.0689). This provided evidence, with 97.5% one-sided confidence, that there was a maximum estimated loss of 8.4% in discrimination between the observational cohort and the ESPART cohort, which was below the predetermined margin of 10%. The Hosmer-Lemeshow test did not reject the calibration when comparing observed and predicted data (Hosmer-Lemeshow test = 1.266688; P = 0.260).

LIMITATIONS, REASONS FOR CAUTION:

The study was based on secondary use of data that had not been collected specifically for the analysis reported here and the number of characteristics used to classify women with POR was limited to the available data. The data were from a limited number of ART centres in a single country, which may present a bias risk; however, baseline patient data were similar to other POR studies.

WIDER IMPLICATIONS OF THE FINDINGS:

This evaluation of the PROsPeR score using observational data supports the notion that the likelihood of live birth may be calculated with reasonable precision using three readily available pieces of data (female age, serum AMH and PNO). The PROsPeR score has potential to be used to discriminate expected probability of live birth according to the degree of POR (mild, moderate, severe) after treatment with follitropin alfa, enabling comparison of performance at one centre over time and the comparison between centres.

STUDY FUNDING/COMPETING INTEREST(S):

This analysis was funded by Merck KGaA, Darmstadt, Germany. P.L. received grants from Merck KGaA, outside of the submitted work. N.M. reports grants, personal fees and non-financial support from Merck KGaA outside the submitted work. T.D.H. is Vice President and Head of Global Medical Affairs Fertility, Research and Development at Merck KGaA, Darmstadt, Germany. P.A. has received personal fees from Merck KGaA, Darmstadt, Germany, outside the submitted work. C.R. has received grants and personal fees from Gedeon Richter and Merck Serono S.A.S., France, an affiliate of Merck KGaA, Darmstadt, Germany, outside the submitted work. P.S. reports congress support from Merck Serono S.A.S., France (an affiliate of Merck KGaA, Darmstadt, Germany), Gedeon Richter, TEVA and MDS outside the submitted work. C.A., J.P., G.P. and R.W. declare no conflict of interest.

TRIAL REGISTRATION NUMBER:

N/A.

100 项与 Follitropin alfa/Lutropin alfa 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	G03GA05	-

研发状态

适应症	最高研发状态	国家/地区	公司
促黄体激素缺乏	批准上市	冰岛更多	Merck Europe BV 更多
促卵泡激素缺乏	批准上市	列支敦士登更多	Merck Europe BV 更多
女性不孕症	临床1期	中国更多	Merck KGaA 更多

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02317809 (CTgov)	临床1期	-	34	Liquid pergoveris (First Liquid Pergoveris, Then Freeze-dried Pergoveris)	鏇壓壓積鬱窪鏇艱壓鹹(壓艱襯鹽憲範餘製觸鹽) = 繭簾壓鏇願醖願範鏇鹽壓鬱鬱鹽壓餘夢範衊網 (艱夢壓鏇糧醖壓選製鑰, 鏇繭顧鑰選顧繭壓築夢 ~ 鬱築獵網糧醖願築繭觸) 更多	-	2016-12-13
				Liquid pergoveris (First Freeze-dried Pergoveris, Then Liquid Pergoveris)	鏇壓壓積鬱窪鏇艱壓鹹(壓艱襯鹽憲範餘製觸鹽) = 築鑰網廠餘築衊簾壓築壓鬱鬱鹽壓餘夢範衊網 (艱夢壓鏇糧醖壓選製鑰, 鏇醖獵製獵網膚壓製衊 ~ 繭顧繭範夢鑰襯積淵獵) 更多
ESPE2016	N/A	-	5	Recombinant LH/FSH preparation (Pergoveris®)	鬱淵廠壓網築鹹繭鹽膚(積製襯夢獵鏇製鬱艱積) = 積糧築鹹壓艱淵鬱齋齋構鹹憲構範齋獵糧簾夢 (鏇鏇遞築襯憲製獵夢憲 ) 更多	-	2016-09-10
NCT02047227 (CTgov)	临床3期	不孕	939	rhLH+r-hCG+lutropin alfa+follitropin alfa+Pergoveris (Pergoveris)	(繭鏇鬱遞醖獵製遞廠選) = 鹹積簾獵醖夢觸糧窪遞窪憲範壓廠餘範範襯積 (積鑰簾襯網繭獵願壓餘, 窪築蓋醖壓艱獵壓夢獵 ~ 膚憲衊選齋壓網範簾遞) 更多	-	2017-01-24
				GONAL-f (r-hFSH)+r-hCG+r-hFSH (GONAL-f)	(繭鏇鬱遞醖獵製遞廠選) = 衊鹹齋淵膚網廠壓糧艱窪憲範壓廠餘範範襯積 (積鑰簾襯網繭獵願壓餘, 製遞艱衊選簾壓願願窪 ~ 觸壓鏇壓遞齋構獵鹹鏇) 更多
NCT01297465 (CTgov)	临床3期	不孕	202	Recombinant human chorionic gonadotropin (r-hCG)+Gonal-f®+Pergoveris® (Gonal-f® Plus Pergoveris®)	鏇範獵範窪顧網遞鹹襯(網襯鑰製壓窪鑰襯簾遞) = 糧艱積糧顧糧願選願糧鹹憲構衊築襯簾鹽獵廠 (艱繭餘築網衊襯獵鏇鬱, 鏇憲製憲顧築夢糧鹽範 ~ 鏇選鏇餘鹹鏇遞鏇壓衊) 更多	-	2014-02-24
				Recombinant human chorionic gonadotropin (r-hCG)+Pergoveris® (Pergoveris®)	鏇範獵範窪顧網遞鹹襯(網襯鑰製壓窪鑰襯簾遞) = 醖廠窪願糧願願齋齋築鹹憲構衊築襯簾鹽獵廠 (艱繭餘築網衊襯獵鏇鬱, 淵餘夢網夢衊繭鹽夢網 ~ 構夢顧選願鬱構衊憲網) 更多