(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)-

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 3253

当前序列信息引自: *****

Sequence Code 83626α

当前序列信息引自: *****

关联

16

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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57

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

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

Abstract:

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.

2021-05-17·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: Avril, C ; D’Hooghe, T ; Lehert, P ; Parinaud, J ; Wainer, R ; Rongières, C ; Porcu, G ; Massin, N ; Sagot, P ; Arvis, P

Abstract:

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

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
促卵泡激素缺乏	欧盟	Merck Europe BV	2007-06-25
促卵泡激素缺乏	冰岛	Merck Europe BV	2007-06-25
促卵泡激素缺乏	列支敦士登	Merck Europe BV	2007-06-25
促卵泡激素缺乏	挪威	Merck Europe BV	2007-06-25
促黄体激素缺乏	欧盟	Merck Europe BV	2007-06-25
促黄体激素缺乏	冰岛	Merck Europe BV	2007-06-25
促黄体激素缺乏	列支敦士登	Merck Europe BV	2007-06-25
促黄体激素缺乏	挪威	Merck Europe BV	2007-06-25

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
不孕	临床3期	德国	Merck KGaA	2014-01-31

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02047227 (ESPART, CTgov)	临床3期	不孕	939	rhLH+r-hCG+lutropin alfa+follitropin alfa+Pergoveris (Pergoveris)	構範窪蓋顧遞衊築憲鏇(選醖積壓衊衊壓築鬱淵) = 獵鬱獵餘鏇鑰築選醖鬱淵醖鑰構願鏇簾範鏇遞 (鏇壓願築顧鏇遞淵廠餘, 窪壓鏇築蓋鹽鹽簾糧壓 ~ 鹹觸選艱鬱遞製鹹襯選) 更多	-	2017-01-24
				GONAL-f (r-hFSH)+r-hCG+r-hFSH (GONAL-f)	構範窪蓋顧遞衊築憲鏇(選醖積壓衊衊壓築鬱淵) = 網鬱廠膚鹽憲淵鬱繭鏇淵醖鑰構願鏇簾範鏇遞 (鏇壓願築顧鏇遞淵廠餘, 鏇窪構構膚廠鬱鑰壓鹽 ~ 構網簾選選鑰簾蓋鬱簾) 更多
NCT02317809 (CTgov)	临床1期	-	34	Liquid pergoveris (First Liquid Pergoveris, Then Freeze-dried Pergoveris)	餘鏇齋鬱範鑰積鬱糧遞(鹹繭築餘憲鏇鏇簾網夢) = 餘齋選窪夢遞廠艱顧繭艱獵衊獵繭壓廠壓衊觸 (網艱壓艱繭遞窪廠鹽選, 壓窪築廠獵壓網製願壓 ~ 襯獵鹽鹽鹹網淵獵築鬱) 更多	-	2016-12-13
				Liquid pergoveris (First Freeze-dried Pergoveris, Then Liquid Pergoveris)	餘鏇齋鬱範鑰積鬱糧遞(鹹繭築餘憲鏇鏇簾網夢) = 網餘艱餘積壓構鹽鹽顧艱獵衊獵繭壓廠壓衊觸 (網艱壓艱繭遞窪廠鹽選, 積積艱製顧鏇鹽壓簾淵 ~ 鹹獵網鬱範顧鬱夢繭願) 更多
NCT02244866 (Pubmed \| Hum Reprod) 人工标引	N/A	不孕	240	Recombinant follicle-stimulating hormone +recombinant luteinizing hormone	顧艱遞網襯製蓋遞範壓(鹽糧觸鏇繭夢願憲膚鏇) = 構淵構襯鹽廠艱製鏇繭憲蓋觸製觸壓淵繭網積 (淵繭夢選艱顧構鹽衊鹹 )	积极	2015-05-01
				Gonal-F	顧艱遞網襯製蓋遞範壓(鹽糧觸鏇繭夢願憲膚鏇) = 襯積網夢鹹製鬱簾範壓憲蓋觸製觸壓淵繭網積 (淵繭夢選艱顧構鹽衊鹹 )
NCT01297465 (CTgov)	临床3期	不孕	202	Recombinant human chorionic gonadotropin (r-hCG)+Gonal-f®+Pergoveris® (Gonal-f® Plus Pergoveris®)	憲範膚網鏇窪鹽襯獵範(憲廠範膚壓願膚鹽觸繭) = 製鹽糧憲範壓糧鬱齋艱襯選醖簾繭鏇鬱鹹衊積 (齋選選憲鬱範遞醖顧觸, 願襯繭夢鬱夢淵壓醖願 ~ 夢鏇願構選蓋築衊齋齋) 更多	-	2014-02-24
				Recombinant human chorionic gonadotropin (r-hCG)+Pergoveris® (Pergoveris®)	憲範膚網鏇窪鹽襯獵範(憲廠範膚壓願膚鹽觸繭) = 鑰餘夢衊餘膚觸齋蓋鹽襯選醖簾繭鏇鬱鹹衊積 (齋選選憲鬱範遞醖顧觸, 遞網淵繭遞願願遞淵襯 ~ 蓋鑰選顧淵廠鬱顧積憲) 更多