A Phase 2, Randomized, Prospective Double-Blind, Single-Center, Placebo-controlled Study to Evaluate Safety, Tolerability, Target Engagement, and Efficacy of PrimeC in Patients With Mild to Moderate Alzheimer's Disease (AD)

20 subjects with mild to moderate AD will be enrolled in the study and randomized at a 1:1 ratio to receive the study drug or placebo tablets, respectively. All subjects will be administered the drug/placebo twice daily (BID), two tablets each time, for 52 weeks.
Subjects will be allowed to receive standard of care (SOC) treatment of approved products or their combination. Subjects will be evaluated every 3 months for safety and tolerability.

开始日期2023-11-19

申办/合作机构

Neurosense Therapeutics Ltd.

NCT05436678 / Completed临床1期

An Open Label, Randomized, Multiple-Dose, Two-Treatment, Two-Period, Two-Sequence, Crossover Study to Evaluate the Comparative Bioavailability of PrimeC (Ciprofloxacin and Celecoxib) Tablets to Ciprofloxacin Tablets Co-administered With Celecoxib Capsules, in Healthy Adult Subject

This is an open-label, randomized, multiple-dose, two-treatment, two-period crossover study comparing the test and reference products. In each period of the study, either 2 × PrimeC tablets or reference products (ciprofloxacin co-administered celecoxib) will be administered to subjects every 12 hours for 6.5 days (13 total administrations), in fed conditions.
The subjects will receive the test treatment in one of the study periods and the reference treatment in the other study period according to a two-sequence randomization schedule. Blood samples will be collected before the morning dose on Day 1, before the morning and evening dose on Days 5 and 6, before the morning dose on Day 7 and at intervals over 48 hours after the morning dose on Day 7 (see Section 7.6) in each study period. Subjects will be confined at the clinical facility from at least 10.5 hours before the initial dose on Day 1 until approximately 48 hours after the final dose on Day 7.

开始日期2022-07-26

申办/合作机构

Neurosense Therapeutics Ltd.

NCT05357950 / Active, not recruiting临床2期

A Phase IIb, Randomized, Multi-Center, Multinational, Prospective, Double-Blind, Placebo-Controlled Study, With an Open Label Extension, to Evaluate Safety, Tolerability and Efficacy of PrimeC in Subjects With ALS

69 subjects with ALS will be enrolled in the study and randomized at a 2:1 ratio to receive the study drug or placebo tablets. Randomization sequences will be in random block sizes and stratified for ENCALS risk category [high risk ≥ -4.5 vs. low risk < -4.5], and for background ALS treatment (riluzole and/or edaravone and/or sodium phenylbutyrate and/or taurursodiol) vs. no background ALS treatment.
All subjects will be administered the drug/placebo twice daily (BID), two tablets each time, for 6 months. Subjects will be allowed to receive standard of care (SOC) treatment of approved products (i.e., riluzole and edaravone). Additionally, subjects will be allowed to receive treatment with off-label sodium phenylbutyrate and taurursodiol, which are accepted for ALS treatment.
Subjects will be evaluated every 2 months for safety, tolerability (adverse events, safety laboratory, vital signs, ECG, withdrawal rates and reasons) and efficacy (e.g. biomarkers, clinical outcomes (ALSFRS-R and SVC, quality of life and survival).
All subjects who complete the 6 months dosing will be switched to the active arm for a 12-month open label extension (OLE).

开始日期2022-05-31

申办/合作机构

Neurosense Therapeutics Ltd.

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100 项与塞来昔布/环丙沙星相关的专利（医药）

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项与塞来昔布/环丙沙星相关的文献（医药）

2023-04-03·Amyotrophic lateral sclerosis & frontotemporal degeneration

Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS

Article

作者: Salomon-Zimri, Shiran ; Russek-Blum, Niva ; Shefner, Jeremy M. ; Paganoni, Sabrina ; Pushett, Avital ; Ennist, David L. ; Drory, Vivian E. ; Berry, James D. ; Van Eijk, Ruben P. A. ; Beaulieu, Danielle ; Eitan, Erez ; Abramovich, Beatrice ; Birman, Nurit ; Elgrart, Katya

OBJECTIVE:

This study aimed to evaluate the safety and tolerability of a fixed-dose co-formulation of ciprofloxacin and celecoxib (PrimeC) in patients with amyotrophic lateral sclerosis (ALS), and to examine its effects on disease progression and ALS-related biomarkers.

METHODS:

In this proof of concept, open-label, phase IIa study of PrimeC in 15 patients with ALS, participants were administered PrimeC thrice daily for 12 months. The primary endpoints were safety and tolerability. Exploratory endpoints included disease progression outcomes such as forced vital capacity, revised ALS functional rating scale, and effect on algorithm-predicted survival. In addition, indications of a biological effect were assessed by selected biomarker analyses, including TDP-43 and LC3 levels in neuron-derived exosomes (NDEs), and serum neurofilaments.

RESULTS:

Four participants experienced adverse events (AEs) related to the study drug. None of these AEs were unexpected, and most were mild or moderate (69%). Additionally, no serious AEs were related to the study drug. One participant tested positive for COVID-19 and recovered without complications, and no other abnormal laboratory investigations were found. Participants' survival compared to their predictions showed no safety concerns. Biomarker analyses demonstrated significant changes associated with PrimeC in neural-derived exosomal TDP-43 levels and levels of LC3, a key autophagy marker.

INTERPRETATION:

This study supports the safety and tolerability of PrimeC in ALS. Biomarker analyses suggest early evidence of a biological effect. A placebo-controlled trial is required to disentangle the biomarker results from natural progression and to evaluate the efficacy of PrimeC for the treatment of ALS. Summary for social media if publishedTwitter handles: @NeurosenseT, @ShiranZimri•What is the current knowledge on the topic? ALS is a severe neurodegenerative disease, causing death within 2-5 years from diagnosis. To date there is no effective treatment to halt or significantly delay disease progression.•What question did this study address? This study assessed the safety, tolerability and exploratory efficacy of PrimeC, a fixed dose co-formulation of ciprofloxacin and celecoxib in the ALS population.•What does this study add to our knowledge? This study supports the safety and tolerability of PrimeC in ALS, and exploratory biomarker analyses suggest early insight for disease related-alteration.•How might this potentially impact the practice of neurology? These results set the stage for a larger, placebo-controlled study to examine the efficacy of PrimeC, with the potential to become a new drug candidate for ALS.

项与塞来昔布/环丙沙星相关的新闻（医药）

2024-05-20

·PRNewswire

NeuroSense Vice President of R&D Shiran Zimri, Ph.D. to Participate in the 3rd Annual ALS Drug Development Summit

CAMBRIDGE, Mass., May 20, 2024 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a company developing novel treatments for severe neurodegenerative diseases, announces that Vice President of R&D, Dr. Shiran Zimri will be a key presenter at the ALS Drug Development Summit in Boston, Mass. on May 22, 2024, which gathers the top drug developers in the field to present findings and collaborate toward a cure for the disease. Continue Reading Dr. Shiran Zimri, VP of R&D at NeuroSense Dr. Zimri will present during a session titled, "Exploring the Potentials of Combination Therapy in ALS & Showcasing Latest Progress of PrimeC," in which she will provide an update on the Company's latest findings from its phase 2b clinical trial (PARADIGM). Dr. Zimri will also be leading and moderating a workshop at the pre-conference event, which will delve into the promising field of combination therapy as a novel approach for the treatment of ALS. "I am thrilled to participate in and speak at this conference. I eagerly anticipate sharing our findings and plans, engaging with participants, and exploring new opportunities. The positive reception from the scientific community regarding the PARADIGM outcomes has been gratifying. We are eager to advance PrimeC to the next stage and share our plans with regulators," stated Shiran Zimri, NeuroSense Therapeutics VP of R&D. More information on the ALS Drug Discovery Summit can be found here. Recently, the Company announced additional results of its PARADIGM trial that included a statistically significant 43% (p=0.02) slowing of disease progression in high-risk ALS patients treated with PrimeC compared to placebo after 6 months. This translates to a 5.04-point difference in ALSFRS-R scores favoring PrimeC (CI: 0.862, 9.214; n=38) in the per protocol population analysis. About ALS Amyotrophic lateral sclerosis ("ALS") is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 patients are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of patients with ALS is expected to grow by 24% by 2040 in the U.S. and EU. About ALSFRS-R Disease progression is measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), which is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person's physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing. A single point change on the ALSFRS-R has a significant impact on ALS patients, such as the transition from independent feeding to requiring assistance or independent breathing to needing to use a machine ventilator. About PARADIGM PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial of the Company's lead drug candidate, PrimeC, in ALS. The trial included 68 participants living with ALS in Canada, Italy, and Israel. 96% of the trial participants who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open label extension. Furthermore, to date all participants that completed the 18-month trial treatment duration, requested to continue PrimeC, which is provided to them in an Investigator Initiated Trial, not limited with time. As previously reported, top-line data from the 6-month double-blind segment of the trial showed clinically meaningful signs of efficacy with a 29% difference in ALSFRS-R (p=0.12) and a 13% difference in SVC (p=0.5), both in favor of PrimeC vs placebo in analysis of the intent to treat (ITT) population. These data include all 68 people living with ALS enrolled in Canada, Italy, and Israel, with the exclusion of one patient who was misdiagnosed. In the PP top-line analysis from PARADIGM, a statistically significant slowing of disease progression was observed with a 37.4% (p=0.03) difference in ALSFRS-R in favor of PrimeC vs placebo. Most patients enrolled in both the active and placebo arms of the trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug. About PrimeC PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ("RNA") regulation to potentially inhibit the progression of ALS. NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency. About NeuroSense NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology company focused on discovering and developing treatments for patients suffering from debilitating neurodegenerative diseases. NeuroSense believes that these diseases, which include amyotrophic lateral sclerosis (ALS), Alzheimer's disease and Parkinson's disease, among others, represent one of the most significant unmet medical needs of our time, with limited effective therapeutic options available for patients to date. Due to the complexity of neurodegenerative diseases and based on strong scientific research on a large panel of related biomarkers, NeuroSense's strategy is to develop combined therapies targeting multiple pathways associated with these diseases. For additional information, we invite you to visit our website and follow us on LinkedIn and X. Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include a statement regarding PrimeC as a potential treatment for people with ALS . Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include unexpected R&D costs or operating expenses, a delay in the reporting of additional results from PARADIGM clinical trial, the timing of expected regulatory and business milestones, risks associated with meeting with the FDA to determine the best path forward following the results from PARADIGM clinical trial, including a delay in any such meeting; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; timing for reporting data; the development and commercial potential of any product candidates of Neurosense; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 4, 2024 and NeuroSense's subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law. Photo: Logo: SOURCE NeuroSense

临床2期临床结果孤儿药

2024-05-14

·PRNewswire

NeuroSense Partners with PhaseV to Optimize Upcoming ALS Phase 3 Trial Using Advanced Causal Machine Learning

PhaseV's Causal Machine Learning Predicts High Probability of Success in Multiple ALS Subgroups for NeuroSense's Phase 3 Trial CAMBRIDGE, Mass., May 14, 2024 /PRNewswire/ -- NeuroSense Therapeutics (Nasdaq: NRSN) ("NeuroSense"), a company developing novel treatments for severe neurodegenerative diseases, today announced that it partnered with PhaseV, a pioneer in causal machine learning (ML) for clinical trial analysis and optimization, with respect to the planned Phase 3 trial of PrimeC as a treatment for amyotrophic lateral sclerosis (ALS). As part of the collaboration, PhaseV conducted an independent analysis of NeuroSense's PARADIGM Phase 2b study using a causal ML and predicts a high probability of success in multiple subgroups for the planned Phase 3 trial of PrimeC as a treatment for ALS. The external results provide important insights that will significantly inform study design, patient enrollment and ensure cost-effectiveness. "There remains a critical need for new innovative approaches to address this devastating neurodegenerative disease," said Alon Ben-Noon, CEO of NeuroSense. "Our recently announced subgroup analysis from the PARADIGM study is very encouraging and suggests the potential of PrimeC to change this reality. Through our initial collaboration with PhaseV, we gained an even greater understanding of the effect of PrimeC across multiple patient subgroups. We will apply these insights to optimize the design of our Phase 3 study with the aim of maximizing meaningful clinical results that will differentiate PrimeC in the market. We plan to continue to collaborate with PhaseV as we develop our Phase 3 trial." NeuroSense Therapeutics recently reported positive efficacy and safety data from its Phase 2b trial (PARADIGM) with its lead drug candidate for ALS, PrimeC, and is planning on embarking on a Phase 3 pivotal trial in the next few months. In addition to PrimeC demonstrating a statistically significant 37% slowing of disease progression, as measured by the ALSFRS-R score (p=0.03), in the per-protocol population from the PARADIGM trial, it also announced a statistically significant slowing of disease progression in high-risk ALS patients treated with PrimeC by 43% (p=0.02) as compared to placebo in the pre-specified per protocol (PP) population analysis after 6 months of treatment. The slowing of disease progression demonstrated by PrimeC versus placebo translates to a 5.04 points difference in the ALSFRS-R in favor of PrimeC (Confidence Interval: 0.862, 9.214; n=38).High-risk patients, defined by the European Network for the Cure of ALS (ENCALS) Risk Factor as those with a higher risk for rapid disease progression, comprise approximately 50% of the total ALS population. NeuroSense soon plans to submit its End of Phase 2 package to the FDA and EMA, including the updated Phase 3 study protocol, which will be discussed in the meetings. "Although there is an improved understanding of the underlying mechanisms of ALS, therapeutic options remain limited due to the complexity and heterogeneity of the disease," said Dr. Raviv Pryluk, CEO and Co-founder of PhaseV. "NeuroSense's ALS drug candidate PrimeC showed great promise in its Phase 2b study. Through a unique combination of causal-ML, real-world data, and advanced statistical methods, we confirmed the potential clinical benefit of PrimeC and provided actionable insights for the Phase 3 study. Our analysis predicted a high rate of success for PrimeC in the Phase 3 clinical trial for multiple recommended subgroups." PhaseV's proprietary technology addresses the challenges of drug development by providing tools for the identification of subgroups and endpoints most likely to succeed in subsequent clinical trials. This has helped companies to better understand how their drug candidates will perform in Phase 3 clinical trials and to optimize the design of the Phase 3 trial accordingly in order to achieve meaningful and successful outcomes. About NeuroSense NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology company focused on discovering and developing treatments for patients suffering from debilitating neurodegenerative diseases. NeuroSense believes that these diseases, which include amyotrophic lateral sclerosis (ALS), Alzheimer's disease and Parkinson's disease, among others, represent one of the most significant unmet medical needs of our time, with limited effective therapeutic options available for patients to date. Due to the complexity of neurodegenerative diseases and based on strong scientific research on a large panel of related biomarkers, NeuroSense's strategy is to develop combined therapies targeting multiple pathways associated with these diseases, with a primary focus on ALS. For additional information, we invite you to visit our website and follow us on LinkedIn. Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding the benefits of the collaboration with Phase V and the timing for a planned End of Phase 2 meeting with the FDA and EMA. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include the risk that the collaboration with Phase V will not bring the expected benefits; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; the development and commercial potential of any product candidates of the company; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense Therapeutics is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 4, 2024 and NeuroSense Therapeutics' subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense Therapeutics Ltd. undertakes no duty to update such information except as required under applicable law. Logo - SOURCE NeuroSense

临床2期临床3期临床结果

2024-05-08

·药明康德

延缓疾病进展43%，渐冻症小分子疗法2b期临床结果积极

NeuroSense Therapeutics今日公布了其2b期临床试验PARADIGM的最新分析结果。分析显示，接受其在研疗法PrimeC治疗的高危肌萎缩侧索硬化（ALS）患者，与安慰剂组相比，疾病进展显著延缓43%（p=0.02）。该公司计划利用这些数据帮助设计即将进行的关键性临床试验，以提高试验成功率。数据分析显示，经过6个月治疗，PrimeC组高危ALS患者的ALS功能评定量表-修订版（ALSFRS-R）评分与对照组相比的差异为5.04分，有利于PrimeC（CI：0.862，9.214；n=38）。根据欧洲ALS治疗网络（ENCALS）风险因素定义，高危患者约占ALS患者总数的50%。在接受治疗前症状持续超过12个月的首次确诊患者中，接受PrimeC治疗的患者与安慰剂组相比，疾病进展延缓52%（p=0.008），ALSFRS-R评分差异为7.76分，有利于PrimeC（CI：2.27，13.25；n=22）。这些亚组分析结果一致显示了PrimeC在PARADIGM研究中对不同组别患者的显著影响。 NeuroSense的主打候选药物PrimeC是一种新型缓释口服制剂，包含两种已获FDA批准的药物：环丙沙星和塞来昔布。PrimeC旨在协同靶向ALS的多种关键机制，包括运动神经元退化、炎症、铁积累和RNA调控障碍，以潜在抑制ALS的进展。PrimeC已获得美国FDA和欧洲药品管理局的孤儿药资格。参考资料：[1] NeuroSense Announces New Positive Data Analysis from PARADIGM Clinical Trial Demonstrating Statistically Significant Slowing of Disease Progression in High-Risk ALS Patients. Retrieved May 7, 2024, from https://www.prnewswire.com/news-releases/neurosense-announces-new-positive-data-analysis-from-paradigm-clinical-trial-demonstrating-statistically-significant-slowing-of-disease-progression-in-high-risk-als-patients-302137999.html 内容来源于网络，如有侵权，请联系删除。

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床2期	以色列	Neurosense Therapeutics Ltd.	2023-11-19
肌萎缩侧索硬化	临床2期	加拿大	Neurosense Therapeutics Ltd.	2022-05-31
肌萎缩侧索硬化	临床2期	以色列	Neurosense Therapeutics Ltd.	2022-05-31
肌萎缩侧索硬化	临床2期	意大利	Neurosense Therapeutics Ltd.	2022-05-31

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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


NCT05357950 (PARADIGM, PRNewswire) 人工标引	临床2期	肌萎缩侧索硬化	68	PrimeC	糧範製鹹鑰範鬱糧獵壓(選蓋簾齋夢窪顧憲觸膚) = PrimeC achieved an improvement in complication-free survival compared to placebo (in several methodologies, including MiToS and King's Advanced Stage-free Survival), reducing the risk of ALS disease complications or death by up to 53%. 構築鏇壓觸繭齋範壓夢 (築膚餘膚膚餘觸鹽壓遞 )	积极	2024-02-21
				Placebo
NCT05357950 (PARADIGM, Biospace) 人工标引	临床2期	肌萎缩侧索硬化	68	PrimeC	願構夢廠鬱鬱觸鏇鹽鹽(範餘鹽範獵蓋齋觸膚夢) = The safety and tolerability profile of PrimeC was comparable to the placebo. 膚淵鹽艱鹽鏇膚淵觸製 (鏇鹹膚製廠淵襯衊顧簾 ) 更多	积极	2023-12-05
				placebo
ASCO2005	临床1期	晚期非小细胞肺癌	15	Celecoxib	範襯鏇夢廠鑰鹽繭糧蓋(憲積鏇壓鹹廠襯艱夢獵) = 窪獵獵簾艱觸衊壓願襯築鏇醖觸夢襯繭鑰積積 (窪簾艱獵窪願鹽膚襯繭 )	-	2005-06-01
				Erlotinib	範襯鏇夢廠鑰鹽繭糧蓋(憲積鏇壓鹹廠襯艱夢獵) = 艱窪齋襯簾獵窪獵餘顧築鏇醖觸夢襯繭鑰積積 (窪簾艱獵窪願鹽膚襯繭 )