A Randomized, Single-Blind, Placebo-Controlled Phase 2a Study to Evaluate the Stimulatory Effects of TAK-448, a Kisspeptin Analog, Administered Intermittently in Middle-aged and Older Men With Low Testosterone

The purpose of this study is to evaluate the effects on serum testosterone (ST) after 6 weeks of subcutaneous (SC) administration of different doses and dosing frequencies of TAK-448 to middle-aged and older men with low ST levels.

开始日期2015-09-10

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT02369796 / Terminated临床2期

An Open-Label, Phase 2a Study to Evaluate the Pharmacodynamics of Different Dosing Regimens of TAK-448, a Kisspeptin Agonist, in Male Overweight/Obese Participants With Hypogonadotropic Hypogonadism

The purpose of this study is to evaluate the effects on serum testosterone after 4 weeks of subcutaneous (SC) dose administration, with different doses and dosing frequencies of TAK-448 to overweight/obese males with hypogonadotropic hypogonadism.

开始日期2015-02-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与 MVT-602 相关的临床结果

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100 项与 MVT-602 相关的转化医学

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100 项与 MVT-602 相关的专利（医药）

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项与 MVT-602 相关的文献（医药）

2023-11-02·Fertility and sterility

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: Results from two randomized, placebo-controlled clinical trials.

Article

作者: Ali Abbara ; Mike Ufer ; Christine Voors-Pette ; Lance Berman ; Max Ezzati ; Rui Wu ; Tien-Yi Lee ; Juan Camilo Arjona Ferreira ; Elizabeth Migoya ; Waljit S Dhillo

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 (KP54) can induce oocyte maturation during in vitro fertilization treatment, including in women at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported.

OBJECTIVE:

To determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (Phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (Phase-2a trial).

DESIGN:

Two randomized, placebo-controlled, parallel group, dose-finding trials.

SETTING:

Clinical trials unit, Netherlands.

PARTICIPANTS:

Healthy women aged 18-35 years, either without (Phase-1; n=24), or with ovarian stimulation (Phase-2a; n=75).

INTERVENTIONS:

Phase-1: Single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n=6 per dose). Phase-2a: Single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n=16-17 per dose), triptorelin 0.2 mg (n=5; active comparator), or placebo (n=5).

MAIN OBJECTIVES AND OUTCOME MEASURES:

Phase-1: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones). Phase-2a: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); time to ovulation assessed by transvaginal ultrasound.

RESULTS:

In both trials, MVT-602 was safe and well-tolerated across the entire dose-range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours. In the Phase-2a trial, LH concentrations increased dose-dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3μg MVT-602 and remained above 15 IU/L for 33 hours. Time to ovulation following drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1μg), 82% (0.3μg), and 75% (0.1μg), of women after MVT-602, 100% after triptorelin, and 60% after placebo.

CONCLUSIONS:

MVT-602 induces LH concentrations of similar amplitude and duration as the physiological mid-cycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR.

TRIAL REGISTRATIONS:

EUDRA-CT: 2017-003812-38, 2018-001379-20.

2022-05-23·Reproductive biology and endocrinology : RB&E

Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction.

Review

作者: Kai-Lun Hu ; Zimiao Chen ; Xiaoxue Li ; Enci Cai ; Haiyan Yang ; Yi Chen ; Congying Wang ; Liping Ju ; Wenhai Deng ; Liangshan Mu

BACKGROUND:

Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis.

MAIN TEXT:

Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome.

CONCLUSION:

More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

2020-12-01·The Journal of clinical investigation1区 · 医学

Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.

1区 · 医学

Article

作者: Ali Abbara ; Pei Chia Eng ; Maria Phylactou ; Sophie A Clarke ; Rachel Richardson ; Charlene M Sykes ; Chayarndorn Phumsatitpong ; Edouard Mills ; Manish Modi ; Chioma Izzi-Engbeaya ; Debbie Papadopoulou ; Kate Purugganan ; Channa N Jayasena ; Lisa Webber ; Rehan Salim ; Bryn Owen ; Paul Bech ; Alexander N Comninos ; Craig A McArdle ; Margaritis Voliotis ; Krasimira Tsaneva-Atanasova ; Suzanne Moenter ; Aylin Hanyaloglu ; Waljit S Dhillo

BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.

项与 MVT-602 相关的新闻（医药）

2022-10-24

·FierceBiotech

Sumitomo nets Myovant in $2.9B buyout, adding IVF asset to pipeline

A deal with Myovant will give Sumitomo control of a pipeline prospect, MVT-602. Sumitomo has landed its takeover target. After seeing Myovant turn down its original offer, the Japanese drugmaker has added almost 20% to its price to get the deal done and snag a phase 2 in vitro fertilization asset. Osaka-based Sumitomo became a major shareholder in Myovant in 2019 and, having seen its partner’s share price fall from above $20 to briefly below $10, made a move to buy the remaining 48% of the drug developer earlier this month. Myovant promptly knocked back the $22.75-a-share offer but left the door open to negotiations. Sumitomo returned with an offer of $27 a share and persuaded Myovant to sign. The deal centers on two commercial products, Orgovyx and Myfembree, but will also give Sumitomo control of a pipeline prospect, MVT-602. Takeda tried and failed to develop the oligopeptide kisspeptin-1 receptor agonist as a treatment for low levels of testosterone and other sex hormones. After missing the endpoints in phase 2 trials, Takeda offloaded the rights to the drug candidate as part of the deal with Roivant Sciences that birthed Myovant. While Takeda studied the molecule, then known as TAK-448, in men with sex hormone disorders, the new partners pitched it for use in female infertility at the time of their deal in 2016. Since then, Myovant has published phase 1 and phase 2a data on the candidate, linking it to a surge in luteinizing hormone associated with high and dose-dependent rates of ovulation. The company framed the data as evidence that MVT-602 could become a safe alternative egg-maturation trigger. Yet the progress of, and investment in, MVT-602 has stalled. In its 2021-22 financial year, Myovant racked up $318,000 in R&D costs specific to the candidate, down from $4.9 million in 2018-19. In theory, Sumitomo, a larger company, has the resources to kick-start development, but it made no mention of the molecule in its statement to disclose the Myovant merger.

并购

2022-10-18

·GlobeNewswire-Health Care

Myovant Sciences Announces New Employment Inducement Grants Under NYSE Rule 303A.08

BASEL, Switzerland, Oct. 18, 2022 (GLOBE NEWSWIRE) -- Myovant Sciences (NYSE: MYOV), a biopharmaceutical company that aspires to redefine care for women and for men through purpose-driven science, empowering medicines, and transformative advocacy, today announced that it approved equity awards for 10 new employees with a grant date of October 17, 2022 pursuant to Myovant’s 2020 Inducement Plan. The equity awards were granted to the employees joining Myovant in accordance with NYSE’s Listed Company Manual Rule 303A.08. The new employees received, in the aggregate, restricted stock units (RSUs) to purchase 96,500 common shares of Myovant. One-fourth of the shares underlying each employee’s RSU will vest on the one-year anniversary of the grant date, with the balance of the common shares vesting in twelve equal quarterly installments thereafter, in each case, subject to each such employee’s continued employment with Myovant on such vesting dates. The RSUs are subject to the terms and conditions of the 2020 Inducement Plan and the applicable RSU agreements. ABOUT MYOVANT SCIENCESMyovant Sciences aspires to redefine care for women and for men through purpose-driven science, empowering medicines, and transformative advocacy. Founded in 2016, Myovant has executed five successful Phase 3 clinical trials across oncology and women’s health leading to three regulatory approvals by the U.S. Food and Drug Administration (FDA) for men with advanced prostate cancer, women with heavy menstrual bleeding associated with uterine fibroids, and premenopausal women with moderate to severe pain associated with endometriosis, respectively. Myovant also has received regulatory approvals by the European Commission (EC) and the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) for women with symptomatic uterine fibroids and for men with advanced hormone-sensitive prostate cancer. Myovant has a supplemental New Drug Application under review with the FDA for updates to the United States Prescribing Information (USPI) based on safety and efficacy data from the Phase 3 LIBERTY randomized withdrawal study (RWS) of MYFEMBREE in premenopausal women with heavy menstrual bleeding due to uterine fibroids for up to two years. Myovant also is conducting a Phase 3 study to evaluate the prevention of pregnancy in women with uterine fibroids or endometriosis. In addition, Myovant is developing MVT-602, an investigational oligopeptide kisspeptin-1 receptor agonist, which has completed a Phase 2a study for female infertility as part of assisted reproduction. Sumitovant Biopharma, Ltd., a wholly owned subsidiary of Sumitomo Pharma Co., Ltd., is Myovant’s majority shareholder. For more information, please visit www.myovant.com. Follow @Myovant on Twitter and LinkedIn. Myovant Sciences ContactsInvestor Contact:Uneek MehraChief Financial and Business OfficerMyovant Sciences, Inc.investors@myovant.com Media Contact:Noelle Cloud DuganVice President, Corporate CommunicationsMyovant Sciences, Inc.media@myovant.com

2022-10-18

·BioSpace

Myovant Sciences Announces New Employment Inducement Grants Under NYSE Rule 303A.08 - October 18, 2022

BASEL, Switzerland, Oct. 18, 2022 (GLOBE NEWSWIRE) -- Myovant Sciences (NYSE: MYOV), a biopharmaceutical company that aspires to redefine care for women and for men through purpose-driven science, empowering medicines, and transformative advocacy, today announced that it approved equity awards for 10 new employees with a grant date of October 17, 2022 pursuant to Myovant’s 2020 Inducement Plan. The equity awards were granted to the employees joining Myovant in accordance with NYSE’s Listed Company Manual Rule 303A.08. The new employees received, in the aggregate, restricted stock units (RSUs) to purchase 96,500 common shares of Myovant. One-fourth of the shares underlying each employee’s RSU will vest on the one-year anniversary of the grant date, with the balance of the common shares vesting in twelve equal quarterly installments thereafter, in each case, subject to each such employee’s continued employment with Myovant on such vesting dates. The RSUs are subject to the terms and conditions of the 2020 Inducement Plan and the applicable RSU agreements. ABOUT MYOVANT SCIENCES Myovant Sciences aspires to redefine care for women and for men through purpose-driven science, empowering medicines, and transformative advocacy. Founded in 2016, Myovant has executed five successful Phase 3 clinical trials across oncology and women’s health leading to three regulatory approvals by the U.S. Food and Drug Administration (FDA) for men with advanced prostate cancer, women with heavy menstrual bleeding associated with uterine fibroids, and premenopausal women with moderate to severe pain associated with endometriosis, respectively. Myovant also has received regulatory approvals by the European Commission (EC) and the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) for women with symptomatic uterine fibroids and for men with advanced hormone-sensitive prostate cancer. Myovant has a supplemental New Drug Application under review with the FDA for updates to the United States Prescribing Information (USPI) based on safety and efficacy data from the Phase 3 LIBERTY randomized withdrawal study (RWS) of MYFEMBREE in premenopausal women with heavy menstrual bleeding due to uterine fibroids for up to two years. Myovant also is conducting a Phase 3 study to evaluate the prevention of pregnancy in women with uterine fibroids or endometriosis. In addition, Myovant is developing MVT-602, an investigational oligopeptide kisspeptin-1 receptor agonist, which has completed a Phase 2a study for female infertility as part of assisted reproduction. Sumitovant Biopharma, Ltd., a wholly owned subsidiary of Sumitomo Pharma Co., Ltd., is Myovant’s majority shareholder. For more information, please visit . Follow @Myovant on Twitter and LinkedIn. Myovant Sciences Contacts Investor Contact: Uneek Mehra Chief Financial and Business Officer Myovant Sciences, Inc. investors@myovant.com Media Contact: Noelle Cloud Dugan Vice President, Corporate Communications Myovant Sciences, Inc. media@myovant.com

100 项与 MVT-602 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11975

研发状态

适应症	最高研发状态	国家/地区	公司
女性不孕症	临床2期	德国更多	Sumitomo Pharma Co., Ltd. 更多
不孕	临床2期	-	Takeda Pharmaceutical Co., Ltd. 更多
性腺机能减退	临床2期	美国更多	Takeda Pharmaceutical Co., Ltd. 更多
继发性睾丸衰竭	终止	英国更多	Takeda Pharmaceutical Co., Ltd. 更多
前列腺癌	终止	日本更多	Takeda Pharmaceutical Co., Ltd. 更多

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适应症

分期

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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


NCT02381288 (CTgov)	临床2期	低睾酮水平	17	TAK-448 Placebo+TAK-448	艱廠繭鑰廠構蓋製製鹹(製築鹽齋遞醖夢鹽膚壓) = 選鹹憲簾鹹壓選衊壓築鏇鹹獵夢鬱繭醖淵顧獵 (餘衊築淵醖餘鑰顧獵醖, 繭顧餘淵網願夢願膚鏇 ~ 選壓淵簾醖夢艱衊願鑰) 更多	-	2017-05-17
NCT02369796 (CTgov)	临床2期	肥胖 \| 继发性睾丸衰竭	15	TAK-448 (TAK-448 3 µg Once Weekly)	夢壓廠艱選網醖壓窪鏇(構選顧鬱觸醖鬱艱簾獵) = 鑰淵願製壓構構鑰夢餘憲齋餘簾鹽構廠鑰鑰襯 (齋膚鑰膚築淵顧襯簾獵, 鏇窪壓壓艱夢鏇構餘艱 ~ 繭鬱遞繭簾獵選膚鑰構) 更多	-	2017-03-31
NCT02369796 (CTgov)	临床2期	肥胖 \| 继发性睾丸衰竭	15	TAK-448 (TAK-448 1 µg Once Weekly)	夢壓廠艱選網醖壓窪鏇(構選顧鬱觸醖鬱艱簾獵) = 膚壓壓積膚艱鏇壓顧鑰憲齋餘簾鹽構廠鑰鑰襯 (齋膚鑰膚築淵顧襯簾獵, 鹽醖觸夢獵鏇襯蓋網憲 ~ 顧鏇顧淵醖簾鹹積遞簾) 更多	-	2017-03-31