A Phase 1, Open-Label, Dose Escalation, and Dose Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CT-01 as Monotherapy and Combination Therapy With Everolimus in Subjects With Intermediate or Advanced Hepatocellular Carcinoma (BCLC Stage B or C) With Preserved Liver Function (Child-Pugh Class A)

This is a Phase 1, open-label, multicenter, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CT-01, administered either as monotherapy or in combination with everolimus. The study population includes subjects with intermediate or advanced hepatocellular carcinoma (HCC) who have progressed on, or are intolerant to, at least one prior line of systemic treatment. All available standard-of-care therapies should have been received, if deemed appropriate by the investigator (unless contraindicated or considered inappropriate by the treating physician). Eligible subjects are classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C and must not be amenable to curative treatment approaches. Only subjects with preserved liver function (Child-Pugh Class A, score 5-6) at screening are eligible. Approximately 141 participants will be enrolled across 20 sites in Europe (France, Spain, and Germany).

开始日期2025-05-26

申办/合作机构-

CTIS2024-511435-10-00

/ Not yet recruiting临床1期

- CT-01-CD-1

开始日期-

申办/合作机构-

100 项与 CT-01 相关的临床结果

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100 项与 CT-01 相关的转化医学

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100 项与 CT-01 相关的专利（医药）

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项与 CT-01 相关的文献（医药）

2025-05-30·ACS Chemical Neuroscience

Discovery of Carbazole and Theophylline-Based Amyloid Inhibitor for the Promotion of Neuroprotection.

Article

作者: Khan, Juhee ; Gharai, Prabir Kumar ; Jaisankar, Parasuraman ; Mallesh, Rathnam ; Ghosh, Surajit ; Garg, Shubham ; Gupta, Sanju

The amyloid-beta 42 (Aβ₄₂) peptide assembles into neurotoxic soluble oligomers and extracellular fibrillary aggregates during the progression of Alzheimer's disease (AD), which ultimately leads to amyloid plaque in the brain, causing major disruption of the neural circuit and leading to the severe loss of memory. Thus, perturbation or inhibition of this process through the development of advanced inhibitors is crucial for the treatment of AD. Here, we adopted an advanced strategy that showcases the design of a carbazole-based chemical inhibitor targeting the Aβ peptide. The new inhibitors are designed in such a way that they can bind selectively with the Aβ₄₂ peptide and inhibit the assembly process and disease progression. Initial assessments using the thioflavin-T assay and molecular docking experiments help screen the carbazole and theophylline-based CT-01 as effective lead molecules, which bind at the N-terminal hydrophobic region of the Aβ₄₂ peptide and inhibit the formation of soluble oligomers and extracellular fibrillary aggregates. Further, FT-IR spectroscopy, CD, TEM, dot blot, and ITC experiments suggest the inhibition potency of CT-01. Finally, the neuroprotection and apoptosis assay confirm that CT-01 reduces amyloid-mediated toxicity in neurons. The serum-stable CT-01 can also protect the NGF-deprived neurons and has the ability to cross the blood-brain barrier.

2018-07-03·Protein and peptide letters4区 · 生物学

Mining and Functional Verification of Calcitonin Genes from the Genome Database

4区 · 生物学

Article

作者: Hu, Jiewei ; Cai, Zailong ; Yang, Shengsheng ; Jiao, Binghua ; Pang, Lin

BACKGROUND:

With more countries in the world entering elderly society, osteoporosis is a common disease among the elderly, especially middle-aged and elderly women. Although calcitonin is an effective drug used to treat osteoporosis in clinical practice, it also exists such problems as high cost, short half-life, and high immunogenicity. Therefore, to explore more efficient calcitonin has important clinical significance.

OBJECTIVE:

Given the emergence of new-generation gene sequencing, numerous genome sequences of marine species have been revealed. This study aimed to identify new, highly active Calcitonins (CTs) from the gene database.

METHODS:

Candidate CT sequences were obtained by BLAST and analyzed. The evolutionary tree of these sequences was constructed using the Neighbor-Joining method of MEGA 7 software. Secondary structures were analyzed by Circular Dichroism (CD). The biological activities of CTs were estimated using the standard of the rat hypocalcemic activity assay in vivo. The half-life and immunogenicity of CT sequences were determined by ELISA. The physicochemical properties of peptides were analyzed with ProtParam and HeliQuest.

RESULTS:

A total of 64 candidate CT gene and amino acid sequences from different species were obtained by BLAST using the salmon CT (sCT) sequence as the query sequence. These sequences were clustered to 27 different CT polypeptide sequences, and then the evolutionary tree was constructed. A total of 13 sequences were selected for chemical synthesis and activity assay. Results showed that although their secondary structures were similar, four types of candidate CTs had 30% higher activities than sCT, three other types had similar activities to sCT, and the remaining four types had much lower activities than sCT. Among the three designed CTs, the activities of CT-01 and CT-02 were at least 50% higher than those of sCT. Furthermore, all three CT sequences had a similar half-life to sCT and lower immunogenicity.

CONCLUSION:

CTs from Monodelphis domestica, Gallus gallus, Ornithorhynchus anatinus, and Carassius auratus had high activities. The exploration and mining of the marine-life genome database can be extremely valuable considering broad application prospect.

2007-05-01·The Journal of infectious diseases2区 · 医学

The Probable Source of Both the Primary Multidrug‐Resistant (MDR) HIV‐1 Strain Found in a Patient with Rapid Progression to AIDS and a Second Recombinant MDR Strain Found in a Chronically HIV‐1–Infected Patient

2区 · 医学

Article

作者: Laura Maroldo ; Ron M Kagan ; Trish Garton ; Scott Gretz ; Eoin Coakley ; Gary Blick ; Paola Greiger-Zanlungo ; Christos Petropoulos

BACKGROUND:

Rapid progression to AIDS after acute infection with a multidrug-resistant (MDR), dual-tropic strain of human immunodeficiency virus type 1 (HIV-1) was reported in a New York City man (hereafter referred to as "NYC") who has sex with men. The probable source of this HIV-1 (hereafter referred to as "CT01") and the development of a recombinant MDR HIV-1 in the source's partner (hereafter referred to as "CT02") are described.

METHODS:

After identification of the epidemiological link of CT01 and CT02 to NYC, viral sequences and phenotypic analyses were compared. Confirmatory genotypic and phenotypic analyses, replicative capacity, and viral coreceptor use were assessed. Viral recombination was assessed using a sliding window technique and phylogenetic tree analysis.

RESULTS:

NYC and CT01 were linked historically and epidemiologically and were genetically confirmed from CT01's samples acquired 2 days before and subsequent to the transmission event. Genotypic, recombination, and phylogenetic analyses suggest CT02 became superinfected by CT01 with subsequent production of a recombinant panresistant HIV-1.

CONCLUSION:

The probable source of a dual-tropic, MDR HIV-1 that was associated with rapid progression to AIDS is illustrated, suggesting progression was not explained by the HIV-1 variant alone. A probable second finding of a chronically infected host becoming superinfected with MDR HIV-1 with subsequent formation of a panresistant recombinant HIV-1 is described. This case illustrates the public health implications of unsafe sex between serodiscordant and seroconcordant partners.

项与 CT-01 相关的新闻（医药）

2025-05-21

·captortherapeutics.com

New Hope in Liver Cancer Treatment – a Clinical Trial of the Innovative Drug CT-01 Has Been Initiated

Captor Therapeutics S.A. has commenced a clinical trial that could revolutionize the treatment of hepatocellular carcinoma (HCC). The mechanism of action of CT-01 is based on Targeted Protein Degradation (TPD) technology. The investigational drug causes the removal of two proteins: GSPT1 and NEK7. Degradation of the GSTP1protein triggers the activation of programmed cell death, apoptosis, while removal of the NEK7 protein targets blocks tumor-promoting inflammation in the Tumor MicroEnvironment (TME). As a result, tumor growth is inhibited and the tumor regression is observed in preclinical models of liver cancer. This innovative approach coud potentially represent a breakthrough in treating patients with advanced hepatocellular carcinoma. For these patients, current treatment options are very limited, and only a small fraction of patients responds to existing therapies. The Phase 1 trial has began in 19 European clinics across Spain, Germany, and France. It is being conducted in collaboration with the global company ICON, a Contract Research Organization (CRO) specialized in conducting clinical trials. Patient safety is being overseen by an independent committee of experts, an Independent Data Monitoring Committee (IDMC), which monitors the study’s progress. The first patient has been dosed with the CT-01 drug candidate at the renowned Barcelona Clinic Liver Cancer (BCLC) – where the standard prognostic staging system and a globally adopted treatment strategy for liver cancer were originally developed. The CT-01 trial is being conducted as an open-label study (meaning both the patient and the physician know that the active drug is being administered, with no placebo control) and features escalating doses of CT-01 in the first part of the trial. The aim of the study is to evaluate safety and to determine the drug dose that will be used in later stages of the trial. Why is this so important? Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. It accounts for about 90% of primary liver tumor cases. Most cases of HCC develop on a background of liver cirrhosis, which further complicates treatment and worsens the prognosis. According to statistics, at advanced stages of the disease (which is how HCC is most frequently diagnosed), only one in five patients will survive 5 years. Projections indicate that by 2030, the number of deaths due to HCC may increase by over 50% compared to 2020. “CT-01 represents an entirely different treatment approach from those used to date, one based on targeted protein degradation therapy that removes proteins critical for tumor survival. For patients with HCC, this could mean the only real chance for a cure. The project has been enthusiastically received by the hepatology community. Physicians who treat hepatocellular carcinoma are hopeful for the emergence of a new therapeutic option that is unmatched by current treatments. Through its unique mechanism of action, CT-01 may help achieve a treatment response in the majority of patients,” said Robert Dyjas, Medical and Clinical Development Director at CTX.

临床1期蛋白降解靶向嵌合体

2024-08-23

·captortherapeutics.com

Captor Therapeutics has applied for approval to conduct a Phase 1 clinical trial in Patients with Hepatocellular Carcinoma

Captor Therapeutics, a biopharmaceutical company developing drugs based on Targeted Protein Degradation (TPD), has applied for approval to conduct a first-in-human Phase 1 clinical trial with CT-01, a compound developed as part of a FENG-funded project entitled: "Discovery and development of a drug candidate for the treatment of hepatocellular carcinoma to eliminate cancer stem cells by induced degradation of an oncogenic transcription factor". The trial will be conducted by ICON PLC under the supervision of Captor Therapeutics. - We have been preparing for many months to make the most important announcement in the CT-01 project, the start of clinical trials. We do so with great satisfaction and a sense of responsibility for the next steps that could bring new treatment options to many patients around the world. Despite significant progress in recent years, treatment options for advanced HCC remain limited. Available systemic treatments are characterized by a moderate response rate and impact on survival, and most patients experience disease progression despite available treatments. As a result, the median survival for patients with metastatic disease is approximately 20 months. Therefore, the treatment of patients with advanced hepatocellular carcinoma remains an unmet medical need," commented Dr. Tom Shepherd, CEO of Captor Therapeutics. The Company's submission is for a planned multi-center, open-label, dose escalation and expansion Phase 1 study. The study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CT-01, both as monotherapy and in combination with everolimus, in patients with moderately to highly advanced HCC (BCLC grade B or C) and preserved liver function (Child-Pugh grade A). The multicenter clinical trial will be conducted at leading European liver cancer centers in Spain, Germany and France. Patients will receive escalating doses of CT-01 orally. The primary objective of the study is to evaluate safety and tolerability following experimental treatment with the drug candidate in patients diagnosed with primary liver cancer and to determine the maximum tolerated dose and/or recommended dose for further phases of clinical trials in monotherapy and combination treatment. In addition, the anti-tumor activity using radiological imaging and serum tumor markers as well as the pharmacokinetic and pharmacodynamic profile of the drug candidate after monotherapy and in combination treatment will be evaluated. - CT-01 is a small molecule protein degrader of GSPT1, NEK7 and SALL4 that has demonstrated anti-tumor activity in several liver cancer models in preclinical studies. In combination with everolimus (an inhibitor of the mTOR pathway, which is often dysregulated in cancer cells), CT-01 demonstrated greater anti-tumor efficacy than CT-01 alone or everolimus as monotherapy. The potential anti-tumor efficacy of CT-01 is based on its novel mechanism of action, which involves the removal of factors that affect tumor cell viability (GSPT1) and potentially stabilize the tumor microenvironment (NEK7). Unlike current therapies that rely on inhibiting angiogenesis or activating the immune system, CT-01 works directly by preventing efficient protein synthesis by cancer cells. This is also important in a mechanism that is independent of the presence of an unfavorable mutation of the TP53 protein," said Michal Walczak, Board Member and CSO of Captor Therapeutics. The goal of the CT-01 project is to develop a drug candidate using targeted protein degradation technology that will halt the progression of hepatocellular carcinoma and provide significant clinical benefit to patients. Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related deaths worldwide. The majority (80-90%) of liver cancers are hepatocellular carcinomas (HCC) that arise from chronic liver disease.

临床1期蛋白降解靶向嵌合体

2024-06-12

·captortherapeutics.com

Captor Therapeutics has signed an agreement for the implementation and funding of Stage II of the CT-01 Project

Captor Therapeutics has signed an agreement for the implementation and funding of the Stage II of the CT-01 Project Captor Therapeutics, a biopharmaceutical company specialized in the development of drugs based on Targeted Protein Degradation ("TPD"), on 12.06.2024 signed an agreement for the implementation and funding of the second stage of its most advanced project, CT-01: "Discovery and development of a new clinical drug candidate for the eradication of cancer stem cel in the treatment of hepatocellular carcinoma, through degradation of oncofetal transcription factor. - Stage II". The agreement approves the extension of the project until March 31, 2026. The decision received is in response to a protest filed in November 2023 by the Company against the originally negative evaluation of the project application. Further Cofinancing in the amount of PLN 6,766,157.95 will be used by the Company for ongoing work on the final formulation of the drug candidate and the start of multi-center clinical trials, still scheduled to begin in 2024. CT-01 is the Company's second implemented in phases Project next to CT-03. The basis of both projects is the application of an innovative approach, i.e. targeted protein degradation (TPD) to fight cancer. In the case of CT-01, the Company has developed a molecule - a triple degrader against proteins: GSPT-1, NEK7 and SALL4 with high anti-cancer activity in xenogeneic models of HCC (Hepatocellular carcinoma), the most common liver cancer worldwide. The therapy being developed by the Company is a response to the very limited treatment options for patients diagnosed with Hepatocellular carcinoma, Currently, the only methods that offer the possibility of a complete cure for this type of cancer are surgery or liver transplantation for which the eligibility criteria are very restrictive. We are confident in the success of Project CT-01 and look forward to the first positive results after administration of our drug. We will keep you informed about the results of the ongoing research

蛋白降解靶向嵌合体

100 项与 CT-01 相关的药物交易

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