PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial"

PALETTE is a perpetual adaptive platform to efficiently study sepsis interventions within 'treatable traits' in all-ages patients enabling prompt evaluation of pandemic treatments. Treatable traits, therapeutic targets identified by phenotypes or endotypes (defined by biological mechanism or by treatment response) through validated biomarkers (measurable characteristic reflecting normal or pathogenic processes, or treatment responses), may include multi-omics, cellular, immune, metabolic, endocrine features, or intelligent algorithms. PALETTE Bayesian adaptive design enables parallel investigations of multiple interventions for sepsis, and quick inclusion of pandemic pathogens. PALETTE's new conceptual model will respond to the challenges of standard approaches, i.e. series of sepsis trials, each investigating one or two interventions, expensive, time consuming, and inappropriate in pandemic context.

Start Date01 Apr 2026

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT05251727

/ TerminatedPhase 1

Double-blind, Placebo-controlled, Randomized, Dose-escalating, Multi-center, Phase 1 Study to Assess the Safety and Tolerability of ART-123 With Leucovorin/5-fluorouracil/Oxaliplatin and Bevacizumab in Metastatic Colorectal Cancer Patients

To evaluate the safety and tolerability of ART-123 in patients with metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy and bevacizumab

Start Date24 Mar 2022

Sponsor / Collaborator

Veloxis Pharmaceuticals A/S

NCT04492436

/ WithdrawnPhase 2

A Randomized, Double-blind, Placebo-controlled, Multi-national, Multi-center, Parallel-group, Phase 2b Assessing ART-123's Effect on Preventing Sensory Symptoms of OIPN in Unresectable mCRC Subjects Receiving Oxaliplatin-containing Chemo

To evaluate the efficacy and safety of ART-123 on sensory symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) in patients with unresectable metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy

Start Date01 Oct 2021

Sponsor / Collaborator

Veloxis Pharmaceuticals A/S

100 Clinical Results associated with Thrombomodulin Alfa (Genetical Recombination)

100 Translational Medicine associated with Thrombomodulin Alfa (Genetical Recombination)

100 Patents (Medical) associated with Thrombomodulin Alfa (Genetical Recombination)

Literatures (Medical) associated with Thrombomodulin Alfa (Genetical Recombination)

01 Dec 2023·Resuscitation Plus

Coagulofibrinolytic effects of recombinant soluble thrombomodulin in prolonged porcine cardiac arrest

Article

Author: Neumar, Robert W ; Cranford, James A ; Greer, Nicholas ; Hsu, Cindy H ; Zhang, Boya ; Tiba, Mohamad Hakam ; Mahmood, Carmen Colmenero ; Leander, Danielle ; McCracken, Brendan M ; Greineder, Colin F

AimTo evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR).MethodsFifteen pigs (n = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis.ResultsIn saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer (p < 0.05 for each). The duration of anticoagulant effect varied depending on the timing of ART-123 administration. Similarly, ART-123 when given prior to cardiac arrest was found to have pro-fibrinolytic effects, increasing free tissue plasminogen activator (tPA, p = 0.02) and decreasing free plasminogen activator inhibitor-1 (PAI-1, p = 0.04).ConclusionA porcine model of prolonged CA/CPR reproduces many of the coagulofibrinolytic abnormalities observed in human cardiac arrest patients. ART-123 demonstrates a combination of anticoagulant and profibrinolytic effects, depending on the timing of its administration relative to cardiac arrest.

01 Aug 2023·Shock

OPTIMAL PLASMA CONCENTRATION OF THROMBOMODULIN ALFA TO TREAT SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION

Article

Author: Takahashi, Hiroyuki ; Nagase, Satoshi ; Katagiri, Fumihiko ; Yamada, Yasuhiko ; Takayanagi, Risa ; Hatoyama-Tanaka, Saori ; Imaura, Masaharu ; Kanno, Hiroshi

ABSTRACTThrombomodulin alfa (TM alfa) has been shown effective for treatment of disseminated intravascular coagulation (DIC) associated with sepsis, although the optimal therapeutic plasma concentration has not been clarified. In the present study, the plasma trough concentration of TM alfa in septic patients with DIC was determined, then the cutoff value for that concentration showing influence on treatment outcome was calculated using a receiver operating characteristic curve. With a cutoff value of 1,010, the area under the curve of the receiver operating characteristic was 0.669 (95% confidence interval, 0.530–0.808), with sensitivity of 0.458 and specificity of 0.882. To evaluate its accuracy, patients were divided into those above or below the cutoff value, and 90-day survival rates were compared. The above-cutoff group showed a significantly higher 90-day survival rate (91.7%) as compared with the below-cutoff group (63.4%) (P = 0.017), with a hazard ratio of 0.199 (95% confidence interval, 0.045–0.871). Interestingly, the incidence of hemorrhagic adverse effects was not significantly different between the groups. Based on these results, the recommended plasma trough concentration of TM alfa for treatment of septic DIC is 1,010 ng/mL, which should minimize the risk of severe bleeding while maximizing the therapeutic effect.

01 Jan 2023·TH Open

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin

Article

Author: Madoiwa, Seiji ; Honda, Goichi ; Kawasugi, Kazuo ; Okamoto, Kohji ; Wada, Hideo ; Takezako, Naoki ; Kawano, Noriaki ; Ikezoe, Takayuki ; Uchiyama, Toshimasa ; Seki, Yoshinobu ; Iba, Toshiaki ; Suzuki, Kei

Background Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype. Objects The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin. Methods The data from 2,839 patients registered in the postmarketing surveillance of thrombomodulin were evaluated. The patients were divided into four groups depending on antithrombin and fibrinogen levels, and the additive effects of antithrombin on thrombomodulin were examined in the groups. Results The DIC score, Sequential Organ Failure Assessment score, and mortality were significantly higher in the DIC group with low-antithrombin/low-fibrinogen than in the DIC groups without either low antithrombin or low fibrinogen. The survival curve was significantly higher in DIC patients with combination therapy than in patients treated with thrombomodulin monotherapy, but this effect was seen only in patients with infection-based DIC. Conclusion DIC patients with low-antithrombin/low-fibrinogen risk poor outcomes, but they can be the target of combination therapy with antithrombin and thrombomodulin as long as the DIC is due to infection.

News (Medical) associated with Thrombomodulin Alfa (Genetical Recombination)

19 May 2021

·www.globenewswire.com

Emerging Drugs for the Chemotherapy Induced Peripheral

Los Angeles, USA , May 19, 2021 (GLOBE NEWSWIRE) -- Emerging Drugs for the Chemotherapy Induced Peripheral Neuropathy Treatment Will Soon Benefit Patients: A Focus on Recent Clinical Trials Chemotherapy-Induced Peripheral Neuropathy Pipeline Report covers a complete clinical trials analysis of 15+ drugs and 15+ companies, which are developing therapies to change the treatment outlook. DelveInsight’s “Chemotherapy Induced Peripheral Neuropathy (CIPN) Pipeline Insight” report provides comprehensive insights about 15+ companies and 15+ pipeline drugs in the Chemotherapy-Induced Peripheral Neuropathy pipeline landscapes. It comprises CIPN pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Chemotherapy Induced Peripheral Neuropathy therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive CIPN pipeline products. Some of the key takeaways of the Chemotherapy Induced Peripheral Neuropathy Pipeline Report Get an overview of pipeline landscape @ CIPN Clinical Trials Analysis Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-dependent adverse effect of many frequently prescribed chemotherapy and biotherapy drugs, including taxanes, platinum-based drugs, vinca alkaloids, thalidomide, bortezomib, and interferon. However, there are currently no approved drugs available to prevent or treat CIPN. Certain chemotherapy drugs are more likely to cause neuropathy. These include platinum drugs, such as oxaliplatin; taxanes, such as docetaxel; vinca alkaloids, such as vincristine; and myeloma treatments, such as bortezomib. Other chemotherapy drugs can also cause neuropathy. Chemotherapy-Induced Peripheral Neuropathy Emerging Drugs PledOx (akacalmangafodipir, SP-04), being developed by Pledpharma (now Egetis Therapeutics AB), is a first in class drug candidate developed for the prevention of nerve damage caused by chemotherapy treatment in colorectal cancer patients. Research and DevelopmentPhase III NCT03654729Phase III (POLAR-M): In October 2018, PledPharma initiated a Phase III, multicenter, double-blind, placebo-controlled study to establish the efficacious dose of PledOx in the prevention of chronic chemotherapy-induced peripheral neuropathy (CIPN) induced by oxaliplatin. This Phase III trial enrolled 291 participants and got completed in August 2020. NCT04034355: Phase III (POLAR-A): In November 2018, PledPharm, in collaboration with Solasia Pharma, initiated a phase III, double-blind, multicenter, placebo-controlled study of PledOx used on top of modified FOLFOX6 (5-FU/FA and Oxaliplatin) to prevent CIPN in the adjuvant treatment of patients with stage III or high-risk stage II colorectal cancer. A total of 301 participants were enrolled in this trial, and this trial was completed in August 2020. ART 123 (recombinant human thrombomodulin alpha, marketed as Recomodulin® in Japan), the company’s lead product candidate, represents a promising new treatment for severe sepsis with coagulopathy. ART-123 is a soluble recombinant human thrombomodulin. ART-123 inhibits the coagulation process by accelerating the activation of protein C by thrombin. The drug is currently in phase 2 of clinical trials for the treatment of Chemotherapy-induced Peripheral Neuropathy Research and DevelopmentPhase IINCT04492436: In July 2021, Asahi Kasei Pharma will initiate a trial titled “A Randomized, Double-blind, Placebo-controlled, Multi-national, Multi-center, Parallel-group, Phase 2b Assessing ART-123's Effect on Preventing Sensory Symptoms of OIPN in Unresectable mCRC Subjects Receiving Oxaliplatin-containing Chemo”. The aim of this study is to compare the efficacy and safety of ART-123 (low and high dose) to placebo on sensory symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) in patients with unresectable metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy. The trial is expected to get completed by July 2024. For further information, refer to the detailed report @ Chemotherapy-Induced Peripheral Neuropathy Pipeline Therapeutics Scope of CIPN Pipeline Drug Insight Key Questions regarding Current Chemotherapy-Induced Peripheral Neuropathy Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customised pipeline report @ Chemotherapy-Induced Peripheral Neuropathy Drugs Pipeline Report Related Reports DelveInsight's CIPN - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. DelveInsight's Chemotherapy-Induced Peripheral Neuropathy (CIPN) Epidemiology Forecast 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology. DelveInsight’s ‘Gene Therapy for Ocular Rare Disease -Market Insights, Competitive Landscape and Market Forecast - 2026’ report delivers an in-depth understanding of the disease. Human Immunodeficiency Virus Type 1 (HIV-1) Infection Pipeline Insights, 2021 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects. DelveInsight’s Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease. DelveInsight' s IgA Nephropathy (IgAN) - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. DelveInsight's IgG4-Related Disease- Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed understanding of historical and forecasted epidemiology. About DelveInsightDelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. It also provides Healthcare Consulting services comprising credible market analysis that will help accelerate the business growth and overcome challenges with a practical approach.

CollaborateSmall molecular drugGene TherapyFirst in Class

100 Deals associated with Thrombomodulin Alfa (Genetical Recombination)

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KEGG	Wiki	ATC	Drug Bank
D06410	-	B01AX	DB05777

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Disseminated Intravascular Coagulation	JP	Asahi Kasei Corp.	25 Jan 2008

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Sepsis	Preclinical	FR	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Preclinical	RS	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Preclinical	CZ	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Preclinical	IL	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Preclinical	PE	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Discovery	PE	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Discovery	IL	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Discovery	CZ	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Discovery	FR	Asahi Kasei Pharma America Corp.	29 Oct 2012
Sepsis	Discovery	RS	Asahi Kasei Pharma America Corp.	29 Oct 2012

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02792842 (CTgov)	Phase 2	Stage III Colon Cancer	79	ART-123 (3-day ART) (ART-123 (3-day ART))	gcueujfdim(auculhbrrb) = srflwotrnx qhacvfsmss (ryophzbztx, rqueciwslp - rnzhfpxsox) View more	-	04 Apr 2024
				ART-123 (1-day ART) (ART-123 (1-day ART))	gcueujfdim(auculhbrrb) = pqcpqsfjfk qhacvfsmss (ryophzbztx, bthasiqlbt - qkafhflsor) View more
NCT02739165 (Pubmed) Manual	Phase 3	Idiopathic Pulmonary Fibrosis	77	corticosteroid+Thrombomodulin Alfa	zmzerakghz(mftqwoelqp) = bnbwjwoumn bsopcbmdim (mhjzsrpern ) View more	Negative	01 May 2020
				corticosteroid+Placebo	zmzerakghz(mftqwoelqp) = litrrkfomq bsopcbmdim (mhjzsrpern ) View more
NCT01598831 (SCARLET, CTgov)	Phase 3	Sepsis \| Blood Coagulation Disorders	816	ART-123 (ART-123)	xvtbecsrgo(dpcnbcyzqp) = waitsomhzi hfgejewrwk (iraqgwqhka, sqxktbsgbn - espqvbokfx) View more	-	21 Apr 2020
				Placebo (Placebo)	xvtbecsrgo(dpcnbcyzqp) = rjreelgula hfgejewrwk (iraqgwqhka, hlovctlhjy - hvbubnmjvk) View more
NCT01598831 (SCARLET, Pubmed \| J Coll Physicians Surg Pak \| JAMA) Manual	Phase 3	Shock, Septic \| Blood Coagulation Disorders	800	Recombinant Human Soluble Thrombomodulin	paicgdzvtp(kbehppdipu) = ohiupqkhmq jaupgschsd (wdgukdqzkj ) View more	Negative	28 May 2019
				Placebo	paicgdzvtp(kbehppdipu) = txlnbhqzmp jaupgschsd (wdgukdqzkj ) View more

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