A Phase 2 Study to Assess the Effect of a Repeated Dose of XF-73 Nasal Gel on the Microbiological Burden of Commensal Staphylococcus Aureus Nasal Carriage in Surgical Patients at Risk of Post-operative Staphylococcal Infections

This study looks at the difference between XF-73 and placebo in reducing the carriage of a bacteria S. aureus in the nose before, during and after heart surgery. Only people who normally have S.aureus in their nose will be enrolled onto the study. This will be confirmed by analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. It is expected 125 people will participate in this study. Participation will be confirmed by analysis of a nasal swab (a cotton bud placed in the nose) before entering the study. XF-73 or placebo will be given 5 times, with an equal chance of participants receiving either XF-73 or placebo. During the hospital stay more nasal swabs will be taken to determine the amount of S.aureus present in the participant's nose. Other tests such as blood samples, blood pressure and an examination of the nose and sense of smell will be performed as part of the safety assessment. After the hospital stay participants will be followed up for 30 days or if a device has been inserted into the body as part of the surgery for 90 days to look at the rates of post-operative infection between the placebo and XF-73 groups. The study will run for about 18 months. During this period, an independent data monitoring committee will review the study to make sure that the balance of benefits and risks of participating in the study does not change.

开始日期2019-08-29

申办/合作机构

Destiny Pharma Plc

NCT02282605

/ Completed临床1/2期

A Phase I/II Randomised, Double-blind, Placebo-controlled, Single Centre Study of the Nasal Decolonisation of Staphylococcus Aureus (SA) and the Safety and Tolerability of Two Concentrations of XF-73 Nasal Gel in Healthy Subjects.

Study to determine the efficacy, safety and tolerability of two concentrations of XF-73 nasal gel in combination with body and face washing with chlorhexidine gluconate cloths in eradicating nasal carriage of Staphylococcus aureus.

开始日期2014-09-01

申办/合作机构

Destiny Pharma Plc

NCT01592214

/ Completed临床1期IIT

A Two-Part Phase I Study to Establish and Compare the Safety and Local Tolerability of Two Nasal Formulations of XF-73 for Decolonization of Staphylococcus Aureus: A Previously Investigated 0.5 mg/g Viscosified Gel Formulation Versus a Modified Formulation

This is a Phase I, multi-center, clinical study of XF-73 to evaluate the local (nasal) safety and tolerability of a modified, thinner lower viscosity formulation of intranasal XF-73 in healthy male and female subjects. In addition, the potential for systemic absorption of XF-73 in the modified, thinner lower viscosity and the previously investigated thicker, higher viscosity formulations and their decolonization efficacy in comparison to placebo will be evaluated. Both parts of the study will be double-blinded and Part 2 will also be placebo-controlled. Primary objective is to establish the safety and tolerability of two concentrations of a modified thinner, lower viscosity nasal formulation of XF-73 and to compare them to a previously investigated, thicker, higher viscosity formulation

开始日期2012-08-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 Exeporfinium Chloride 相关的临床结果

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100 项与 Exeporfinium Chloride 相关的转化医学

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100 项与 Exeporfinium Chloride 相关的专利（医药）

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项与 Exeporfinium Chloride 相关的文献（医药）

2024-11-01·INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY

Exeporfinium chloride (XF-73) nasal gel significantly reduces Staphylococcus aureus nasal carriage in cardiac surgery patients throughout surgery and the early recovery period: results from a randomized placebo-controlled Phase 2 study

Article

作者: Rhys-Williams, William ; Martina, Yuri ; Gonzalez Moreno, Jesus ; Dane, Aaron ; Barker, Debra ; Firstenberg, Michael S ; Love, William G ; Lees, James P ; Mangino, Julie E

Abstract:

Staphylococcus aureus nasal carriers were randomized (1:1) to XF-73 or placebo nasal gel, administered 5x over ∼24hrs pre-cardiac surgery. S. aureus burden rapidly decreased after 2 doses (–2.2log10 CFU/mL; placebo –0.01log10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo (P = 0.045).

2023-07-01·Infection control and hospital epidemiology

Exeporfinium chloride (XF-73) nasal gel dosed over 24 hours prior to surgery significantly reduced Staphylococcus aureus nasal carriage in cardiac surgery patients: Safety and efficacy results from a randomized placebo-controlled phase 2 study

Article

作者: Milewski, Rita K C ; Rhys-Williams, William ; Dane, Aaron ; Firstenberg, Michael S ; Mangino, Julie E ; Love, William G ; Gonzalez Moreno, Jesus ; Lees, James P

Abstract:

We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log10 with XF-73 compared to 0.4 log10 CFU/mL for those who received placebo (95% CI, −2.7 to −1.5; P < .0001).

2023-01-01·Infection and drug resistance

Efficacy of a Novel Antibacterial Agent Exeporfinium Chloride, (XF-73), Against Antibiotic-Resistant Bacteria in Mouse Superficial Skin Infection Models

Article

作者: Yao, Zhi ; Zhang, Chenrui ; Wang, Song ; Fu, Zheng ; Li, Jinping ; Lu, Rong

Background:

The number of incidences of antimicrobial resistance is rising continually, necessitating new and effective antibacterial drugs. The present study aimed to assess the in vitro and in vivo activity of XF-73 against antibiotic-resistant Staphylococcus aureus (S. aureus) isolates and to investigate the potential mechanism of action of XF-73.

Methods:

The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. Two different superficial Staphylococcal skin infection murine models were established to study the in vivo efficacy of XF-73 against antibiotic-resistant strains. The effect of XF-73 on the ultrastructure and cellular morphology of S. aureus was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM).

Results:

The MICs (minimum inhibitory concentration) determined by the broth microdilution method for XF-73 demonstrated that the compound had a high potency against S. aureus isolates with varying susceptibility to the study drugs. Also, the antibacterial activity of XF-73 was superior or similar to most of the tested antibacterial drugs. We also found that the XF-73 dermal formulation significantly inhibited S. aureus survival in both the murine skin tape-stripping and suture superficial skin infection models, maintained a consistently high inhibitory capacity against the antibiotic-resistant strains tested and was significantly more effective than mupirocin ointment, a commonly used antibiotic for the treatment of skin infections. The morphological studies using TEM suggest that XF-73 had a rapid (2 minute) bacterial cell wall disruption activity, with longer incubation (10 minute) subsequently causing membrane damage. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis.

Conclusion:

Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting.

项与 Exeporfinium Chloride 相关的新闻（医药）

2024-07-15

·FierceBiotech

Destiny goes private to stay afloat after no partner found for anti-infection drug

Like many biotechs, Destiny has struggled on the public markets in recent years. Destiny Pharma’s search for a partner to take its nasal infection prevention med into phase 3 has come up short, leading the British biotech to go private to avoid liquidation. Destiny was one of the few biotechs to choose to list in London in recent years, joining the AIM exchange via a £15.3 million ($19.8 million at the time) offering in 2017. The Brighton, U.K.-based company’s pitch was to use the money to fund the phase 2b trial of XF-73, a nasal drug designed to prevent post-surgery staphylococcal infections. That trial read out in 2021, showing that XF-73 Nasal—a synthetic dicationic porphyrin drug called exeporfinium chloride—produced a more than 99% reduction in nasal bacterial load when compared to placebo, hitting the study’s primary endpoint. But the biotech has struggled to find a partner to take the asset into phase 3 development. With money tight, Destiny has been advised that its best chance of getting an infusion of equity is to return to being a private company. “While there can be no guarantee, the board believes that the only viable option now available to Destiny Pharma to create future shareholder value is the pursuit of capital as a private company,” Nigel Rudd, chair of Destiny’s board of directors, explained in a July 15 release. “Without taking this route, we believe that liquidation of the company is the most likely alternative,” Rudd added. Destiny entered 2024 with £6.4 million ($8.3 million) in cash and equivalents, and notified investors as far back as April that despite engaging with “a number of potential partners” and receiving “some strong and positive feedback” about XF-73 Nasal, the company had been unable to nail down a licensing partner. One stumbling block for potential partners was the anticipated phase 3 trial costs, as well as the general view that antibiotics have limited commercial potential, Destiny explained at the time. To this end, the company pledged to work to “enhance the attractiveness” of XF-73 with a new trial design that should halve the clinical costs. Despite the best efforts of CEO Chris Tovey, who moved across to Destiny from Jazz Pharmaceuticals in September 2023, to “vigorously pursue a potential licensing deal,” there is still no partner in sight. “Although we continue to speak to partners about this renewed proposition, we are extremely disappointed that a deal has not been forthcoming and, given our shortening cash runway, have been forced to amend our strategy as we seek to continue to progress this important product,” Tovey said in this morning’s release. Like many biotechs, Destiny has struggled on the public markets in recent years. The company’s stock rested comfortably above the one pound mark in 2021, but has declined since and despite a rally towards the end of 2023, now sits at just two pence per share. Destiny will put its delisting proposal to shareholders at a meeting later in July.

临床3期临床2期引进/卖出

2024-04-25

·FierceBiotech

Destiny calls time on SporeGen COVID collab, while Santhera hands lonodelestat back to Spexis

Destiny’s biggest concern right now is finding someone to help take forward XF-73. Both Destiny Pharma and Santhera Pharmaceuticals used their earnings announcements this morning to explain why a tighter clinical focus will come at the expense of one of their potential assets. In Destiny’s case, the company has decided not to extend its collaboration with SporeGen past the pre-agreed conclusion point this month. The two British biotechs had been working on a nasal spray of Bacillus bacteria that could work as a preventive treatment for COVID-19. The phase 1 candidate, dubbed SPOR-COV, has already been shown by SporeGen to provide 100% protection in preclinical models of influenza, according to Destiny’s website. But Destiny confirmed today that it would not be taking the collaboration any further as it “focus[es] resources on development of the XF platform and our other key company pipeline programs.” Destiny’s biggest concern right now is finding someone to help take forward XF-73, an antibiotic designed to prevent post-surgery infections. “The company has engaged with a number of potential partners and has received some strong and positive feedback on XF-73 nasal,” Destiny explained in the earnings release. “However, no potential licensing deal has, to date, been forthcoming that we believe would provide fair value to the company and its shareholders.” One stumbling block for potential partners are the anticipated phase 3 trial costs, as well as the general view that antibiotics have limited commercial potential, according to Destiny. To this end, the company is working to “enhance the attractiveness” of XF-73 with a new trial design that should halve the clinical costs. Destiny will also review “strategic options” for the asset, although at the moment these won’t stretch to putting the whole company up for sale. “XF-73 nasal has enormous market potential and can make a huge difference in the prevention of surgical site infections, and the reduction in the usage of antibiotics,” said CEO Chris Tovey in the release. “Whilst we will now be presenting an enhanced proposition for the product to potential partners, we also have initiated a wider review to evaluate a range of strategic options to progress the programme and to maximise value from XF-73 nasal,” Tovey added. In the case of Santhera, the writing was already on the wall for the lung disease candidate lonodelestat long before the Swiss biotech finally pulled the plug. Back in 2022, the company was already warning that available resources were being channeled to its Duchenne muscular dystrophy prospect vamorolone, leaving lonodelestat’s prospects dependent on finding fresh funding from somewhere. While the vamorolone dream became a reality when Santhera scored FDA approval last year, lonodelestat was left to languish. Focusing on the DMD drug, rebranded as Agamree, means Santhera has no time for lonodelestat. With internal development of the human neutrophil elastase inhibitor still on pause, Santhera finally confirmed in this morning’s earnings release that it is terminating work completely and will return lonodelestat to fellow Swiss biotech Spexis. “This has no further financial impact on the 2023 accounts, as an impairment was already recognized under development costs in the 2022 consolidated income statement,” Santhera pointed out.

临床1期上市批准

2023-02-24

·FierceBiotech

Destiny seals C. diff therapy's phase 3 fate with Sebela

Destiny Pharma CEO Neil Clark said a deal with Sebela Pharmaceuticals is in line with the company’s strategy to find partner companies to take their lead assets into late-stage development. Destiny Pharma could be in line for $570 million thanks to a new co-development agreement with U.S.-based Sebela Pharmaceuticals for a Clostridium difficile treatment. The two companies have agreed to work on NTCD-M3 together, with Sebela offering $1 million upfront, development milestones of $19 million and revenue-based milestones of up to $550 million, according to a Friday press release. Royalties are also included. Sebela will gain the North American rights to the treatment and lead and finance clinical development and commercialization activities in the region. U.K.-based Destiny will retain rights in Europe and the rest of the world and will complete ongoing manufacturing of clinical trial supplies for an upcoming phase 3 study. NTCD-M3 is Destiny’s lead asset under development to prevent C. difficile infection recurrence and was in-licensed in 2020. The therapy is an oral formulation of NTCD-M3 spores and protects the gut from the proliferation of toxic strains of C. difficile. A phase 3 study is expected to start in 2024, according to the release. Destiny’s CEO Neil Clark said the deal is in line with the company’s strategy to find partner companies to take their lead assets into late-stage development and reduce funding requirements. Meanwhile, Destiny used the opportunity to announce a fundraising of up to 8 million pounds sterling ($9.5 million) consisting of a placing, subscription and an open offer. The funds will help Destiny complete the required phase 3 work for NTCD-M3 as well as prep XF-73 Nasal for a phase 3 study. The treatment is being developed for preventing post-surgical staphylococcal hospital infections including MRSA.

临床3期引进/卖出

100 项与 Exeporfinium Chloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

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
术后感染	临床2期	美国	Destiny Pharma Plc	2019-08-29
术后感染	临床2期	塞尔维亚	Destiny Pharma Plc	2019-08-29
手术伤口感染	临床2期	美国	Destiny Pharma Plc	2019-08-29
手术伤口感染	临床2期	塞尔维亚	Destiny Pharma Plc	2019-08-29
葡萄球菌感染	临床2期	美国	Destiny Pharma Plc	2019-08-29
葡萄球菌感染	临床2期	塞尔维亚	Destiny Pharma Plc	2019-08-29
金黄色葡萄球菌感染	临床2期	英国	Destiny Pharma Plc	2014-09-01

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临床结果

适应症

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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


NCT03915470 (CTgov)	临床2期	手术伤口感染 \| 术后感染 \| 葡萄球菌感染	124	XF-73 (XF-73)	鬱鹹鏇構鏇鹹觸願淵夢(觸艱鬱獵網鑰夢窪獵選) = 選膚繭築衊選網繭選獵簾襯網簾積艱範網繭膚 (憲構構淵艱選膚齋顧遞, 1.8552) 更多	-	2022-06-01
				Placebo (Placebo)	鬱鹹鏇構鏇鹹觸願淵夢(觸艱鬱獵網鑰夢窪獵選) = 憲顧醖構醖鹽壓蓋願製簾襯網簾積艱範網繭膚 (憲構構淵艱選膚齋顧遞, 1.3697) 更多
NCT01592214 (Pubmed \| J Glob Antimicrob Resist) 人工标引	临床1期	金黄色葡萄球菌感染	60	XF-73	齋壓觸襯壓壓醖糧鹽網(醖繭網範齋築鹹鏇遞製) = 顧鏇鬱艱廠糧齋鬱衊鏇製築醖網糧繭築壓醖壓 (餘壓製構網鏇獵糧鏇膚 )	积极	2020-06-01
NCT02282605 (CTgov)	临床1/2期	金黄色葡萄球菌感染	60	Chlorhexidine gluconate 2% topical cloths+XF-73 nasal gel (XF-73 2.0 mg/g Nasal Gel)	簾製築構淵鏇繭蓋膚網 = 鹽夢製廠簾簾淵艱衊製鏇築艱醖鹹襯醖衊夢網 (膚願遞蓋夢範廠窪製廠, 窪淵蓋齋糧網壓襯蓋蓋 ~ 願窪蓋選壓製糧蓋艱繭) 更多	-	2016-10-07
				Chlorhexidine gluconate 2% topical cloths+XF-73 nasal gel (XF-73 0.5 mg/g Nasal Gel)	簾製築構淵鏇繭蓋膚網 = 願窪製網艱獵獵淵衊衊鏇築艱醖鹹襯醖衊夢網 (膚願遞蓋夢範廠窪製廠, 觸醖鹹膚淵艱遞鬱糧築 ~ 選壓鑰鹽簾獵憲齋夢壓) 更多