A Phase 2 Open-label Multi-centre Study to Evaluate the Efficacy and Safety of Oxabact® to Reduce Plasma Oxalate in Subjects With Primary Hyperoxaluria Who Are on Dialysis

The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering plasma oxalate levels in patients with primary hyperoxaluria who are on dialysis.

开始日期2014-05-19

申办/合作机构

OxThera AB

NCT01037231

/ Completed临床2/3期

A Phase 2/3, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of OxabactTM to Reduce Urinary Oxalate in Subjects With Primary Hyperoxaluria.

The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria.

开始日期2009-12-01

申办/合作机构

OxThera AB

100 项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的临床结果

登录后查看更多信息

100 项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的转化医学

登录后查看更多信息

100 项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的专利（医药）

登录后查看更多信息

项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的文献（医药）

2023-02-01·Pediatric nephrology (Berlin, Germany)3区 · 医学

ePHex: a phase 3, double-blind, placebo-controlled, randomized study to evaluate long-term efficacy and safety of Oxalobacter formigenes in patients with primary hyperoxaluria

3区 · 医学

Article

作者: Jarraya, Faical ; Banos, Ana ; Lindner, Elisabeth ; Abroug, Saoussen ; Gould, Edward ; Ben Hmida, Mohamed ; Schalk, Gesa ; Ariceta, Gema ; Fraga, Gloria ; Dehmel, Bastian ; De, Sudarsana ; Moochhala, Shabbir H ; Hunley, Tracy E ; Collard, Laure ; Boussetta, Abir

Abstract:

Background:

Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH.

Methods:

Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1.73 m2) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint.

Results:

Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was − 3.80 μmol/L; 95% CI: − 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments.

Conclusions:

Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0.06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones.

Graphical abstract:

A higher resolution version of the Graphical abstract is available as Supplementary information.

2021-07-23·Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2区 · 医学

Effects of Oxalobacter formigenes in subjects with primary hyperoxaluria Type 1 and end-stage renal disease: a Phase II study

2区 · 医学

Article

作者: Hoppe, Bernd ; Dehmel, Bastian ; Lindner, Elisabeth ; Herberg, Ulrike ; Pellikka, Patricia A ; Banos, Ana

Abstract:

Background:

In primary hyperoxaluria Type 1 (PH1), endogenous oxalate overproduction significantly elevates urinary oxalate excretion, resulting in recurrent urolithiasis and/or progressive nephrocalcinosis and often early end-stage renal disease (ESRD). In ESRD, dialysis cannot sufficiently remove oxalate; plasma oxalate (Pox) increases markedly, inducing systemic oxalate deposition (oxalosis) and often death. Interventions to reduce Pox in PH1 subjects with ESRD could have significant clinical impact. This ongoing Phase II, open-label trial aimed to evaluate whether long-term Oxabact™ (Oxalobacter formigenes, OC5, OxThera Intellectual Property AB, Sweden) lowers Pox in PH1 ESRD subjects, ameliorating clinical outcome.

Methods:

PH1 ESRD subjects on stable dialysis regimens were examined. Subjects were administered one OC5 capsule twice daily for up to 36 months or until transplantation. Total Pox values, cardiac function and safety were evaluated. Free Pox was evaluated in a comparative non-treated PH1 dialysis group using retrospective chart reviews and analyses.

Results:

Twelve subjects enrolled in an initial 6-week treatment phase. Following a washout of up to 4 weeks, eight subjects entered a continuation study; outcomes after 24 months of treatment are presented. After 24 months, all subjects had reduced or non-elevated Pox compared with baseline. Cardiac function improved, then stabilized. No treatment-related serious adverse events were reported.

Conclusions:

Compared with an untreated natural control cohort, 24 months OC5 administration was beneficial to PH1 ESRD subjects by substantially decreasing Pox concentrations, and improving or stabilizing cardiac function and clinical status, without increasing dialysis frequency. OC5 was safe and well-tolerated.

2019-05-01·Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry3区 · 化学

Endophytic actinomycetes Streptomyces spp mediated biosynthesis of copper oxide nanoparticles as a promising tool for biotechnological applications

3区 · 化学

Article

作者: Awad, Mohamed A ; Salem, Salem S ; Fouda, Amr ; Barghoth, Mohammed G ; Hassan, Saad El-Din ; Abdo, Abdullah M ; Radwan, Ahmed A ; El-Gamal, Mamdouh S

In this study, two endophytic actinomycetes isolates Oc-5 and Acv-11, were isolated from healthy leaves of medicinal plant Oxalis corniculata L. These isolates were identified as Streptomyces zaomyceticus Oc-5 and Streptomyces pseudogriseolus Acv-11 using 16S rRNA gene sequence. Biomass extract of these strains were used as a greener attempt for synthesis of copper oxide nanoparticles (CuO-NPs). The synthesized NPs were characterized by UV-Vis spectroscopy, Fourier transform infra-red (FT-IR) spectroscopy, X-ray diffraction (XRD)' transmission electron microscopy (TEM), energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS). Green synthesized NPs showed surface plasmon resonance (SPR) absorption band at 400 nm, crystalline nature, spherical-shaped with an average size of 78 nm and 80.0 nm for CuO-NPs synthesized using strain Oc-5 and Acv-11, respectively. The bioactivities of CuO-NPs were evaluated. Results revealed that CuO-NPs exhibited promising antimicrobial activity against prokaryotic and eukaryotic microbial cells (Gram positive bacteria, Gram negative bacteria, unicellular and multicellular fungi). In addition, it showed antimicrobial potential against phyto-pathogenic fungal strains Fusarium oxysporum, Pythium ultimum, Aspergillus niger and Alternaria alternata. We further explored the in vitro antioxidant activity and cytotoxicity for biosynthesized CuO-NPs. The results revealed that' scavenging and total antioxidant activity for NPs synthesized using Streptomyces pseudogriseolus Acv-11 was better than those synthesized by Streptomyces zaomyceticus Oc-5. Also, the morphological changes and cell viability for Vero and Caco-2 cell line due to NPs treatments were assessed using MTT assay method. Furthermore, Larvicidal efficacy against Musca domestica and Culex pipiens was evaluated. The results obtained in this study clearly showed that biosynthesized CuO-NPs exhibited effective bioactivity and, therefore, provide a base for the development of versatile biotechnological applications soon.

项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的新闻（医药）

2025-01-08

·PRNewswire

1cBio and Alesta Therapeutics Announce Exclusive Global Licensing Agreement for a Novel Potentially First-in-Class Small Molecule for Hypophosphatasia

SAN FRANCISCO and LEIDEN, Netherlands, Jan. 8, 2025 /PRNewswire/ -- 1cBio, Inc. ("1cBio") an emerging biotech company developing precision medicines for significant unmet needs, and Alesta Pharmaceuticals ("Alesta") a leader in developing first-in-class small molecules for rare diseases, announced an exclusive worldwide licensing agreement. Under this agreement, Alesta will develop, commercialize, and manufacture OC-1(also known as ALE1), an orally active therapeutic candidate for hypophosphatasia (HPP). HPP is a rare genetic disorder caused by mutations in the ALPL gene, leading to defective bone and tooth mineralization. This results in skeletal abnormalities, fragile bones, early tooth loss, and, in older patients, significant muscle weakness, fatigue, and pain. Affecting tens of thousands of patients worldwide, HPP is believed to be underdiagnosed, particularly in older populations. OC-1 is a novel oral therapeutic that inhibits a novel target to reduce levels of inorganic pyrophosphate (PPi), a key metabolite driving disease pathology. Currently progressing through GLP toxicology studies, OC-1 is expected to enter clinical trials in the second half of 2025. OC-1 was developed by combining 1cBio's expertise in medicinal chemistry and translational sciences with thought partners in clinical and basic sciences to guide its innovation. "We are excited to partner with Alesta Therapeutics, who is pioneering the development of transformative medicines for rare disease and can help us to reach HPP patients more rapidly," said Andrew Wong, Chief Executive Officer at 1cBio. "OC-1 is another example of the 1cBio team's capabilities to identify white spaces in disease treatments and develop highly differentiated molecules for precision medicine. We look forward to collaborating with Alesta's innovative development team to efficiently progress a potentially first-in-class, oral therapy for HPP patients." "With the support of 1cBio, the expertise and commitment of our team, and collaborations with leading academics and disease advocacy groups, we are poised to make significant strides in addressing the unmet needs of HPP patients," said Ilan Ganot, Chief Executive Officer of Alesta Therapeutics. "We look forward to advancing OC-1 toward clinical proof of concept and bringing us closer to delivering this transformative therapy to address the entire spectrum of HPP in this underserved disease." Under the terms of the agreement, Alesta will assume responsibility for Phase I preparation activities, including submission of the Clinical Trial Application (CTA) and Investigational New Drug (IND) application, and all subsequent clinical-development activities and global commercialization activities. 1cBio is eligible to receive potential development, regulatory and commercial milestone payments, including an equity investment, and tiered royalties on global sales, contingent upon successful development and commercialization. About 1cBio 1cBio is an emerging biotechnology company which strives to identify white spaces in cancer therapies and develop molecules that can serve as precision medicines. The company's programs are geared to treat the disease and preemptively counter mechanisms for acquired or intrinsic resistance. Core expertise in medicinal chemistry and translational sciences along with thought partners in clinical and basic sciences guides 1cBio's innovation. 1cBio's second lead program is OC-3, a selective-PARP1 inhibitor with the potential to be best-in-class for HR-deficient and HR-proficient tumors when combined with approved targeted therapies. For more information, visit . About Alesta Therapeutics Alesta Therapeutics is a Netherlands-based biotechnology company committed to developing novel oral small molecule therapies for underserved rare diseases. The company's lead asset, ALE1, is being developed for hypophosphatasia (HPP), a rare genetic disorder with significant unmet needs. Alesta is also advancing ALE2, a promising candidate to treat Charcot-Marie-Tooth (CMT) disease. In January 2025 Alesta announced a €65 million Series A financing supported by leading biotech and life science investors. For more information, visit . SOURCE 1cBio WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

引进/卖出临床1期

2023-10-13

·CPHI制药在线

研发 | 浅谈原发性高草酸尿症治疗进展

关注并星标CPHI制药在线原发性高草酸尿症（PH）是一种常染色体隐性遗传病，临床上以尿草酸排泄增加、反复草酸钙尿石形成、肾钙质沉着和全身不溶性草酸盐沉积为特征。PH发病是因基因突变导致肝脏产生过量草酸引起，根据基因突变类型的不同，PH可分为3型。其中Ⅰ型PH（PH1）与2号染色体上AGXT 基因突变有关。AGXT基因编码丙氨酸乙醛酸转氨酶(AGT)，该酶可将乙醛酸转化为甘氨酸，其缺乏可使乙醛酸在细胞质中积聚，从而导致乙醇酸和草酸增多。 Ⅱ型PH（PH2）与10号染色体上GRHPR基因突变有关。GRHPR基因编码乙醛酸羟基丙酮酸还原酶 (GRHPR)，该酶可将乙醛酸转化为乙醇酸，其缺乏会导致乙醛酸积聚，最终被乳酸脱氢酶 (LDH) 转化为草酸。 Ⅲ型PH（PH3）与9号染色体上HOGA1基因突变有关。HOGA1基因编码4-羟基2-酮戊二酸醛缩酶，其缺乏会限制4-羟基2-酮戊二酸转化为乙醛酸，这将使更多的酮戊二酸转向草酸途径。这三种类型中，PH1最常见且最严重，约占80%，据统计全球约有5.8万例PH1患者。而PH2和PH3分别占10%。目前，PH治疗手段有限，包括药物/保守治疗、透析治疗、肝肾联合移植等。其中肝肾联合移植治疗效果有限，且复发率高，患者需要终身免疫抑制以防止器官排斥。治疗药物方面，PH患者直到2020年才迎来首款药物，即Alnylam制药公司的Oxlumo(Lumasiran)。该药是一种皮下给药的RNA干扰(RNAi)疗法，其靶向编码乙醇酸氧化酶的HAO1基因，通过沉默HAO1，从而耗尽乙醇酸氧化酶，抑制草酸的生成。2020年11月，该药被FDA批准用于治疗PH1，以降低儿科和成人患者的尿草酸盐水平。2022年11月，该药又被FDA批准用于治疗PH1，以降低儿童和成人患者的尿草酸盐和血浆草酸盐水平。今年9月，FDA又批准一款PH新疗法，即诺和诺德的Rivfloza（Nedosiran）。该药是Dicerna利用专有GalXC™RNAi技术平台开发的RNAi疗法，通过与表达肝乳酸脱氢酶（LDH）的mRNA结合发挥作用。2021年11月，诺和诺德通过收购Dicerna，将nedosira纳入囊中。已公布的2期临床试验PHYOX™结果显示：接受Nedosiran治疗的PH患者（包括PH1和PH2）的尿草酸盐排泄量与基线差值相较于安慰剂组具有统计学意义(p＜0.0001)差异。而且，与安慰剂相比，接受Nedosiran治疗的患者在第90天后两次或更多次连续随访时达到并维持正常或接近正常Uox水平的比例显著更高（p=0.0025）。 Lumasiran和Nedosiran均属于RNAi疗法，但适应症稍有差异，Nedosiran适应症人群更加广泛，不局限于PH1患者。此外，目前全球还有几款在研PH新疗法，如Chinook Therapeutics的CHK-336、OxThera的Oxabact、BridgeBio的BBP-711。其中CHK-336是一款肝脏靶向的口服LDHA抑制剂，在PH1小鼠模型实验中能有效地将尿液中草酸含量降至正常水平，且展现出良好的安全性。已公布的CHK-336治疗PH和其他肾结石疾病的1期临床试验结果显示：CHK-336通常耐受性良好，具有良好的药代动力学特征，其半衰期支持每日一次的给药频率。而且，研究人员利用新型示踪剂证明了CHK-336能够阻断健康受试者肝脏草酸盐的生成。值得一提的是，今年6月，诺华斥资35亿美元收购Chinook Therapeutics，将包括CHK-336在内的多款药物纳入囊肿。 Oxabact是一种双模式肠道生物疗法，是含有产甲草酸杆菌的冻干制剂，以包衣胶囊形式口服给药。通过促进草酸盐从血浆主动和被动分泌到肠道，Oxabact能够增加草酸盐的排泄。遗憾的是，2021年6月，OxThera宣布Oxabact治疗PH的关键3期临床试验OC5-DB-02错失主要终点。 BBP-711是一种口服给药的乙醇酸氧化酶 (GO) 小分子抑制剂。靶向GO是一种经过临床验证的方法，可通过降低乙醛酸的浓度来减少尿中的草酸。BBP-711治疗高草酸尿症的首次人体1期试验已于2021年5月启动。整体来看，PH领域还存在很大未满足的市场需求，虽然诺和诺德Rivfloza已于近日获批。期待随着企业的不懈努力，PH领域可以早期迎来更多新疗法。扫码参与制药在线周年庆游园会来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

临床2期临床结果并购信使RNA临床3期

2021-06-11

·BioSpace

OxThera reports results from Phase 3 ePHex study with Oxabact in primary hyperoxaluria patients with maintained kidney function

STOCKHOLM, June 11, 2021 /PRNewswire/ -- OxThera AB, a privately-held biopharmaceutical company dedicated to improving the lives of people with Primary Hyperoxaluria (PH), announces completion of its pivotal Phase 3 study and reports top line results. OxThera's 52-week OC5-DB-02 study "A Phase III Double-Blind, Randomised Study to Evaluate the Long-Term Efficacy and Safety of Oxabact® in Patients with Primary Hyperoxaluria" (ePHex) enrolled patients with all types of PH, who had to have a plasma oxalate (Pox) concentration ≥ 10 μmol/L and an eGFR < 90 ml/min/1.73 m2 during screening to be eligible for inclusion into the study. Twenty-five patients were enrolled and randomly assigned 1:1 to either Oxabact (13) or placebo (12). Almost all patients (24) had been diagnosed with PH type 1, only 1 patient with PH type 2. The mean age at baseline for all subjects was 15.5. years (range 5 to 54 years), patients in the Oxabact arm were slightly younger. Baseline mean plasma oxalate in the two treatment arms was well balanced, 14.8 µmol/L in Oxabact and 14.4 µmol/L in placebo. Urinary oxalate excretion was slightly higher in the Oxabact group vs placebo; 2.10 and 1.76 mmol/day/1.73 m2, respectively. The mean Pox concentration, the primary endpoint of the study, separated after week 24 in favor of Oxabact. The estimate of mean (SE) difference between treatment arms reached – 3.8 (2.0) μmol/L (95% CI -7.8 – 0.2) at week 52 (p=0.06), where the Oxabact group was essentially stable, and placebo increased. A trend in favor of Oxabact was observed for the overall comparison, and this was consistent across most pre-defined sub-groups. A supportive slope model demonstrated a similar magnitude of change (SE) of -6.1 (3.0) µmol/L (p=0.04). Adverse events were well balanced between the 2 treatment arms, there were slightly more severe adverse events observed in the placebo arm than in the Oxabact arm. "We are encouraged that the observed treatment effect towards the end of the study supports our hypothesis behind the mechanism of action of Oxabact, but of course disappointed that it did not reach statistical significance" said Elisabeth Lindner, Chief Operating Officer of OxThera. "Oxabact is an oral formulation of the bacterium Oxalobacter formigenes metabolizing oxalate that enters the GI tract through active and passive secretion from plasma. The hypothesis is that treatment with Oxabact could stop or delay disease progression. It appears that the study was not long enough to detect a difference in clinical endpoints, and OxThera is now seeking a partner to further develop Oxabact." Key secondary endpoints of the study, kidney function (estimated glomerular filtration rate, eGFR) and the number of adjudicated kidney stone events during the study, did not show a significant difference between treatment groups. During the 3 years pre-dose, 9 patients in the Oxabact arm reported in total 18 or more stone events, and 7 patients in placebo reported in total 16 or more stone events. On study, 7 stone events occurred in 13 Oxabact patients and 8 stone events in 12 placebo patients. "As a physician treating patients with PH, it is of primary importance to me that my patients are stable." said Dr. Gema Ariceta, Principal Investigator at Val d'Hebron hospital, Barcelona, Spain, and highest recruiter of patients in the ePHex study. Six out of 8 enrolled patients at her study site were randomized to Oxabact during the study. "Even if I am disappointed that the study did not meet significance, I think it is important to look at individual patients in such a rare disease and to see if treatment effects can be seen. The safety profile of Oxabact, as well as oral administration, would make it a good background treatment candidate for patients." The study results have been accepted for oral presentation at the upcoming European Society of Pediatric Nephrology meeting, 16-19. September 2021, Amsterdam, and will be presented by Dr. Ariceta on Saturday, 18. September, in Session 16 (Hall 2) between 16:45 - 18:30. For further information, please contact: Elisabeth Lindner, COO E-mail: Elisabeth.lindner@oxthera.com About Oxabact® Oxabact is a bi-modal enteric biotherapy containing a lyophilized formulation of Oxalobacter formigenes, a non-pathogenic, oxalate-degrading commensal bacterium. Oxabact is administered orally as a coated capsule. By promoting active and passive secretion of oxalate from the plasma into the gut, Oxabact is able to increase excretion of oxalate. Oxabact is a registered trademark of OxThera Intellectual Property AB. About OxThera OxThera AB is a Swedish biopharmaceutical company developing a new treatment for primary hyperoxaluria (PH) - a rare genetic and devastating disease with fatal outcomes. This information was brought to you by Cision The following files are available for download: View original content: SOURCE OxThera

100 项与 Lyophilised Oxalobacter formigenes(OxThera AB) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
原发性高草酸尿症	临床3期	美国	OxThera AB	2007-10-01
肾结石	临床2期	德国	OxThera AB	2013-07-10

登录后查看更多信息

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


NCT02000219 (CTgov)	临床2期	原发性高草酸尿症	12	Oxalobacter formigenes	齋鏇願窪顧鏇艱襯襯鬱(積觸鹽選糧糧醖壓觸願) = 遞簾糧製壓製淵鹹範憲構鹹餘繭築齋選糧積鹹 (淵構蓋鏇鬱構壓構觸選, 39.63) 更多	-	2021-12-09
NCT03116685 (CTgov)	临床3期	原发性高草酸尿症	25	Oxabact OC5 - Oxalobacter formigenes HC-1 (Oxabact OC5 Capsules)	遞顧網憲願遞積衊艱製(衊繭顧範醖觸選醖壓繭) = 簾憲顧憲壓願衊夢製襯繭構願鹹鬱齋築鏇艱衊 (顧窪醖衊製製簾壓夢膚, 5.7) 更多	-	2021-12-09
NCT03116685 (CTgov)	临床3期	原发性高草酸尿症	25	Placebo (Placebo Capsules)	遞顧網憲願遞積衊艱製(衊繭顧範醖觸選醖壓繭) = 衊遞顧網夢鹽積範夢壓繭構願鹹鬱齋築鏇艱衊 (顧窪醖衊製製簾壓夢膚, 5.4) 更多	-	2021-12-09