A Phase III, Randomized, Open-label, Controlled Trial to Investigate the Efficacy and Safety of UB-421 Monotherapy as Substitution for Stable Antiretroviral Therapy in HIV-1 Infected Adults

The purpose of this phase III study is to evaluate the efficacy, safety and tolerability of UB-421 monotherapy in suppressing viral rebound in HIV-1 infected adults undergoing antiretroviral treatment interruption.

开始日期2025-04-01

申办/合作机构

联合生物制药股份有限公司

NCT04985890 / Not yet recruiting临床2期

A Proof of Concept Study to Evaluate the Safety and Efficacy of UB-421 in Combination With Chidamide for Reduction of HIV Reservoir as Compared to UB-421 Alone in ART Stabilized HIV-1 Patients Who Undergo ART Interruption

To assess the impact of UB-421 and chidamide in changing HIV-1 viral reservoir profile among HIV-1 suppressed patients who undergo short-term ART interruption.
To evaluate the safety and tolerability of UB-421 combined with chidamide among HIV-1 suppressed patients who undergo short-term ART interruption.

开始日期2024-03-01

申办/合作机构

聯生藥大中華控股有限公司

NCT04620291 / Not yet recruiting临床1期

A Phase I, Open-Label, Multi-Dose Study for Evaluation of the Safety, Pharmacokinetics, and Antiviral Activity of UB-421 Subcutaneous Formulation in HIV Infected Adults

UB-421 subcutaneous formulation (UB-421 SC) is developed to provide HIV infected patients a more convenient drug delivery method. UB-421 SC injection, with significantly less injection time than IV infusions and with opportunity of self-administration or administered in general medical setting (in addition to HIV-specific clinic), can provide patient a more convenient option.
This UB-421 SC phase I study will be conducted to investigate short-term safety, pharmacokinetics and anti-viral activity of UB-421 SC at three dose levels in ART-treated aviremic subjects and treatment naive HIV-infected subjects. The current UB-421 SC formulation (125 mg/ml) is at least 10-fold more concentrated than UB-421 IV (10 mg/ml). The highly concentrated formulation makes weekly UB-421 subcutaneous injections feasible. This study will form the basis of UB-421 SC in combination with antiretroviral agents (ARV) for treating HIV infected viremic patients in the future clinical trials.

开始日期2023-12-31

申办/合作机构

联合生物制药股份有限公司

100 项与 Semzuvolimab 相关的临床结果

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100 项与 Semzuvolimab 相关的转化医学

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100 项与 Semzuvolimab 相关的专利（医药）

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项与 Semzuvolimab 相关的文献（医药）

2024-07-09·ACS Omega

Engineering of the Central Core on DBD-Based Materials with Improved Power-Conversion Efficiency by Using the DFT Approach

Article

作者: Akhter, Muhammad Salim ; Mahal, Ahmed ; Khera, Rasheed Ahmad ; Waqas, Muhammad ; Shaban, Mohamed ; Bhatti, Ijaz Ahmad ; Zulfiqar, Aamna ; Ashour, Adel ; Alotaibi, Hadil Faris ; Shawky, Ahmed M. ; Duan, Meitao ; Imran, Muhammad ; S Alshomrany, Ali

Developing proficient organic solar cells with improved optoelectronic properties is still a matter of concern. In the current study, with an aspiration to boost the optoelectronic properties and proficiency of organic solar cells, seven new small-molecule acceptors (Db1-Db7) are presented by altering the central core of the reference molecule (DBD-4F). The optoelectronic aspects of DBD-4F and Db1-Db7 molecules were explored using the density functional theory (DFT) approach, and solvent-state calculations were assessed utilizing TD-SCF simulations. It was noted that improvement in photovoltaic features was achieved by designing these molecules. The results revealed a bathochromic shift in absorption maxima (λ_max) of designed molecules reaching up to 776 nm compared to 736 nm of DBD-4F. Similarly, a narrow band gap, low excitation energy, and reduced binding energy were also observed in newly developed molecules in comparison with the pre-existing DBD-4F molecule. Performance improvement can be indicated by the high light-harvesting efficiency (LHE) of designed molecules (ranging from 0.9992 to 0.9996 eV) compared to the reference having a 0.9991 eV LHE. Db4 and Db5 exhibited surprisingly improved open-circuit voltage (V _OC) values up to 1.64 and 1.67 eV and a fill factor of 0.9198 and 0.9210, respectively. Consequently, these newly designed molecules can be considered in the future for practical use in manufacturing OSCs with improved optoelectronic and photovoltaic attributes.

2024-06-01·EBioMedicine

Ex vivo sensitivity to broadly neutralizing antibodies and anti-CD4 antibody UB-421 of infectious viral isolates from people living with multidrug-resistant HIV

Article

作者: Justement, Jesse S ; Moir, Susan ; Pau, Alice K ; Kennedy, Brooke D ; Manning, Maegan R ; Blazkova, Jana ; Sneller, Michael C ; McLaughlin, Mary ; Rai, M Ali ; Chun, Tae-Wook ; Shi, Victoria

BACKGROUND:

People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking.

METHODS:

We examined levels of immune activation and exhaustion markers on CD8⁺ T cells and the intact HIV proviral DNA burden in 11 PLWH with MDR viruses. For comparison purposes, we included a control group consisting of 27 ART-naïve viremic PLWH. In addition, we determined the sensitivity of infectious viral isolates obtained from the participants against eight bNAbs (3BNC117, 10-1074, VRC01, VRC07, N6, 10E8, PGDM1400, and PGT121) and two anti-CD4 antibodies (ibalizumab and UB-421) using a TZM-bl-based neutralization/suppression assay.

FINDINGS:

The level of intact HIV proviral DNA was comparable between the two groups (P = 0.29). The levels of activation and exhaustion markers PD-1 (P = 0.0019), TIGIT (P = 0.0222), 2B4 (P = 0.0015), CD160 (P = 0.0015), and CD38⁺/HLA-DR⁺ (P = 0.0138) were significantly lower in the MDR group. The infectious viral isolates from each study participant with MDR HIV were resistant to at least 2 bNAbs; however, they were sensitive to at least one of the CD4-binding and non-CD4-binding site antibodies. The majority of participants had ibalizumab-sensitive viruses although the isolates from some participants showed reduced sensitivity to ibalizumab. Notably, none of the 93 viral isolates obtained from the participants were resistant to UB-421.

INTERPRETATION:

Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials.

FUNDING:

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

2021-07-03·Expert opinion on emerging drugs2区 · 医学

Emerging drugs for the treatment of HIV/AIDS: a review of 2019/2020 phase II and III trials

2区 · 医学

Review

作者: Cossu, Maria Vittoria ; Piscaglia, Marco ; Passerini, Matteo ; Rizzardini, Giuliano ; Petri, Francesco ; Fusetti, Chiara ; Capetti, Amedeo ; Gerbi, Martina

Introduction: The study of emerging drug trials to treat people living with HIV (PLWH) helps to understand any advantages and disadvantages of therapies that will be available on the market in the short-term future as well as the mechanisms underlying a better cure.Areas covered: This review analyzes phase 2 and 3 clinical trials published between 2019 and 2020 concerning six different emerging drugs. The majority of the trials focus on long acting drugs, but also on new orally administered compounds.Expert opinion: The biggest news in antiretroviral therapy (ART) is the approval of cabotegravir/rilpivirine as a complete long-acting (LA) therapeutic regimen. It paves the way for an innovation that may change the paradigms of HIV treatment in the long term, albeit it will not be obvious to implement and treatment adherence still needs to be fully evaluated. Results of phase 3 Islatravir trials are awaited. Lenacapavir may soon reach phase 3. These drugs may pave the way for 6-month ART in the next future. Fostemsavir has been recently approved. Albuvirtide, a fusion inhibitor approved in China, presents several limitations for its intravenous use only. UB-421 and VRC01 are monoclonal antibodies against HIV. This emerging technology has shown interesting results but needs further studies.

项与 Semzuvolimab 相关的新闻（医药）

2023-07-14

·Pharmaceutical Technology

Gilead, CHAI and Penta to enhance HIV treatment for children

Gilead will transfer the technology for F/TAF’s dispersible dosage. Credit: Sundry Photography / Shutterstock.com. Gilead Sciences has entered into public-private collaborations with the Clinton Health Access Initiative (CHAI) and the Penta ID network to expedite the development and marketing of dispersible HIV treatments for the paediatric population. The initial collaboration will focus on developing an experimental dispersible paediatric dosage with emtricitabine and tenofovir alafenamide (F/TAF). Recommended Reports Reports LOA and PTSR Model - Semzuvolimab in Human Immunodeficiency Virus (HIV) Infections (AIDS) GlobalData Reports LOA and PTSR Model - Budigalimab in Human Immunodeficiency Virus (HIV) Infections (AIDS) GlobalData View all Companies Intelligence Gilead Sciences Inc Chai, Inc. TAF View all The second partnership aims to create investigational formulations of TAF and sofosbuvir (SOF) by removing the bitter taste to become more palatable to children. The fixed-dose combination therapy will be developed for paediatric HIV patients from low and middle-income countries with a minimum body weight of 3kg. Gilead will transfer the technology for F/TAF’s dispersible dosage while Penta will focus on creating pharmacokinetic (PK) modelling and clinical trials for the experimental formulation. CHAI will oversee the treatment’s international access approach through a partnership with two generic manufacturers. To detect bitterness blockers for TAF and SOF’s paediatric dosages, Gilead is also collaborating with the Monell Chemical Senses Center, the translational cell models group of Eurofins, and CHAI. Gilead Sciences HIV clinical development vice-president Jared Baeten stated: “By developing medicine formulations that meet the needs of children, and by improving palatability, through these partnerships we have the ability to potentially increase adherence rates in children. “This collaboration, along with the recent launch of Gilead’s paediatric centre of excellence in Dublin, reflects our deep commitment to the discovery and development of urgently needed treatment options for children living with HIV and other viral infections across the world.” In February 2023, Gilead received the US Food and Drug Administration’s approval for Trodelvy (sacituzumab govitecan-hziy) to treat breast cancer.

上市批准临床研究免疫疗法

2022-10-28

·阿斯利康中国

Camizestrant在SERENA-2 II期试验中与芙仕得相比，显著提高了晚期雌激素受体阳性乳腺癌患者无进展生存期

试验结果更坚定了阿斯利康对新一代口服SERD开发计划的决心 SERENA-2 II期试验的积极高水平结果表明，阿斯利康的新一代口服选择性雌激素受体下调剂(ngSERD) Camizestrant达到了主要终点，与芙仕得（通用名：氟维司群）500mg剂量相比，Camizestrant的75mg和150mg两种剂量用于既往接受过内分泌治疗的绝经后雌激素受体（ER）阳性的局部晚期或转移性乳腺癌患者时，无进展生存（PFS）均具有统计学意义和临床意义。 Camizestrant耐受性良好，其安全性与之前试验中观察到的一致，没有发现新的安全性信号。乳腺癌是全球最常见的癌症，在2020年约有230万患者被诊断乳腺癌 1 。约70%的乳腺癌是HR+/HER2低表达或阴性 2 。内分泌疗法是HR+晚期乳腺癌最常用的一线治疗方案，并且通常与CDK4/6抑制剂联合应用。然而，许多晚期乳腺癌患者对CDK4/6抑制剂和现有的内分泌疗法产生耐药性，导致其治疗选择有限，因此需要更多的治疗方案。 3 西班牙巴塞罗那Vall d'Hebron肿瘤研究所和SERENA-2 II期试验的首席研究员Mafalda Oliveira博士表示：“SERENA-2的结果表明，Camizestrant与氟维司群相比可显著改善无进展生存期，后者近20年来一直被用于治疗HR阳性乳腺癌患者。这些结果很有意义，突出了新一代口服SERD的潜力，并支持正在进行的研究计划。” 阿斯利康全球执行副总裁，肿瘤治疗领域研发负责人Susan Galbraith表示：“我们的新一代口服SERD Camizestrant的目标是改进目前可用于HR阳性早期和转移性乳腺癌患者的内分泌疗法。SERENA-2试验令人兴奋的疗效和令人信服的安全性结果强调了 Camizestrant在ER驱动的乳腺癌患者中实现这一目标的潜力，我们期待继续推进我们针对 Camizestrant的全面III期临床计划。” 相关数据将在即将召开的医学会议上公布。阿斯利康拥有针对Camizestrant在晚期乳腺癌的广泛临床开发计划，包括关键的 SERENA-6 III 期试验，评估Camizestrant与细胞周期蛋白依赖性激酶 4/6 (CDK4/6) 抑制剂（哌柏西利或阿贝西利）联合用于在一线治疗中检测到ESR1突变的HR阳性转移性乳腺癌患者，以及SERENA-4 III 期试验，评估Camizestrant联合哌柏西利从一线治疗开始治疗HR阳性、局部晚期或转移性乳腺癌。 SERENA-6研究的适应症已获得美国食品和药物管理局授予快速通道资格。阿斯利康拥有一系列全面丰富的已批准和正在开发中的用于治疗乳腺癌患者的新药。除了这些结果，公司还宣布了AKT激酶抑制剂Capivasertib针对HR阳性晚期乳腺癌患者的CAPitello-291 III期试验的积极结果。 ### 关于HR阳性乳腺癌 HR阳性乳腺癌（表达雌激素或孕激素受体，或两者兼有）是最常见的乳腺癌亚型，HR 阳性乳腺癌细胞的生长通常由ER驱动 2,4,5 。针对ER驱动疾病的内分泌疗法被广泛用于晚期乳腺癌的一线治疗，通常与周期蛋白依赖性激酶(CDK)4/6抑制剂联合 3 。然而，许多晚期疾病患者对CDK4/6抑制剂和目前内分泌疗法产生耐药性，治疗方案也不明确 3 。优化内分泌治疗和克服ER驱动疾病患者的耐药抑制是乳腺癌领域研究的重点。关于SERENA-2 SERENA-2是一项随机、开放标签、平行组、多中心 II 期试验，评估Camizestrant的几个剂量水平与氟维司群相比在晚期ER阳性、HER2阴性乳腺癌中的效果。主要终点是评估Camizestrant（75mg）与氟维司群（500mg）、 Camizestrant（150mg）与氟维司群的无进展生存（PFS），其中PFS的定义为实体瘤 (RECIST) 版本 1.1反应评估标准定义的 PFS。240名患者被随机分配接受Camizestrant或氟维司群直至疾病进展。次要终点包括24周的安全性、客观缓解率和临床受益率 (CBR)。 SERENA-2属于一个更大临床项目的一部分，该项目聚焦Camizestrant，评估其作为单药或与其他药物联合使用时的安全性和有效性，以解决HR阳性乳腺癌的许多未满足需求。关于Camizestrant Camizestrant是一种有效的下一代口服SERD和纯ERα拮抗剂，已在一系列临床前模型中显示出抗癌活性，包括那些具有ER激活突变的模型。 SERENA-1 I期试验表明，当单独使用或与CDK4/6抑制剂哌柏西利联合使用时，Camizestrant具有良好的耐受性并且具有良好的抗肿瘤作用。SERENA-1试验中正在探索与其他组合的研究。关于阿斯利康在乳腺癌领域的研究随着对乳腺癌生物学的日益了解，阿斯利康开始挑战和重新定义乳腺癌的分类及临床治疗模式，以提供给患者所需的更为精准而有效的治疗方案。阿斯利康雄心勃勃，希望有朝一日可以消除乳腺癌这一致死病因。阿斯利康研发了一系列已获批或有望获批的药物，通过多种机制应对乳腺癌肿瘤微环境的生物多样性。凭借德曲妥珠单抗(trastuzumab deruxtecan，简称T-DXd)，一种靶向HER2的抗体偶联药物，阿斯利康和第一三共的目标是改善先前治疗的HER2阳性和HER2低表达转移性乳腺癌的结果，并正在探索其在更早线的治疗和新型乳腺癌中的潜力。在HR阳性乳腺癌中，阿斯利康继续持续基石药物氟维司群和戈舍瑞林改善预后，并旨在通过 ngSERD Camizestrant和潜在新药AKT激酶抑制剂Capivasertib重塑HR阳性乳腺癌治疗。同时，阿斯利康与第一三共合作，探索 TROP2靶向ADC datopotamab deruxtecan的潜在效果。 PARP抑制剂奥拉帕利是一种靶向治疗选择，已在遗传性BRCA突变的HER2阴性早期和转移性乳腺癌患者中进行了研究。阿斯利康和默沙东持续探索奥拉帕利在BRCA遗传突变的转移性乳腺癌患者中的效果，同时正寻求新的契机使这类患者在疾病更早期接受治疗。为了满足三阴性乳腺癌患者对更多治疗选择的迫切需求，阿斯利康正在评估免疫药物度伐利尤单抗与奥拉帕利、T-DXd等与其他肿瘤药物联合用药的效果，评估AKT激酶抑制剂Capivasertib与化疗联用，Capivasertib和datopotamab deruxtecan联用的潜在效果。关于阿斯利康在肿瘤领域的研究阿斯利康正引领着肿瘤领域的一场革命，致力提供多元化的肿瘤治疗方案，以科学探索肿瘤领域的复杂性，发现、研发并向患者提供改变生命的药物。阿斯利康专注于最具挑战性的肿瘤疾病，通过持续不断的创新，阿斯利康已经建立了行业领先的多元化的产品组合和管线，持续推动医疗实践变革，改变患者体验。阿斯利康以期重新定义癌症治疗并在未来攻克癌症。声明本文涉及研究中的药品用法尚未在中国获批适应症，阿斯利康不推荐任何未被批准的药品使用。内容来源：新闻稿（内部审批号：CN-104871）参考文献： 1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660. 2. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available at https://seer.cancer.gov/statfacts/html/breast-subtypes.html . Accessed October 2022. 3. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer . 2020; 10.7150/jca.48944. 4. Bae SY, et al. Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer . 2015; 10.1186/s12885-015-1121-4. 5. Lumachi F, et al. Current medical treatment of estrogen receptor-positive breast cancer. World J Biol Chem . 2015; 10.4331/wjbc.v6.i3.231.

免疫疗法抗体药物偶联物抗体合作

2022-09-05

·BioSpace

FDA Review: Immusoft, BioCryst, Intellia and More

Sarah Silbiger/Getty Images The U.S. Food and Drug Administration had a busy week leading up to the Labor Day holiday. Here’s a look at the agency’s recent activities. Sept 1 Immusoft’s IND for a Phase I trial of ISP-001, being developed to treat mucopolysaccharidosis type I, was granted the FDA’s green light. It is the first-ever engineered B cell therapy to enter the clinic, the company reported. eCential Robotics received FDA 501(k) clearance for its 3D imaging, navigation and robotics guidance system. Aston Sci. obtained FDA approval to initiate a Phase II trial of AST-301, a therapeutic cancer vaccine, in patients with triple-negative breast cancer. BioCryst Pharmaceuticals received Orphan Drug Designation for BCX9250, which is being developed to treat fibrodysplasia ossificans progressiva (FOP). Intellia Therapeutics was granted Orphan Drug Designation for its in vivo CRISPR/Cas9 genome editing candidate NTLA-2002 for hereditary angioedema (HAE). Revelle Aesthetics received extended FDA clearance for its precision cellulite release device Aveli. It is now indicated for long-term reduction in the appearance of cellulite in the buttocks and thigh areas of adult women. GenBody America announced the FDA had amended its EUA for the GenBody COVID-19 Ag kit, which was updated to include prefilled individual reagent tubes for each device. Aug 31 Longeveron received Fast Track Designation for Lomecel-B for Hypoplastic Left Heart Syndrome (HLHS). Sanofi reported the FDA-approved Xenpozyme (olipudase alfa-rpcp) for adult and pediatric patients with acid sphingomyelinase deficiency (ASMD), also called Niemann-Pick disease. The company also received Priority Review for its BLA for efanesoctocog alfa for the treatment of hemophilia A. The PDUFA date is February 28, 2023. United BioPharma received the go-ahead for a Phase II trial. The IND was submitted by NIAID to evaluate the antiviral activity of UB-421 in combination with optimized background ART in HIV-1 patients with multi-drug resistance. UB-421 is an anti-CD4 antibody. Scilex Holding Company, a subsidiary of Sorrento Therapeutics, received Fast Track Designation for SP-103, a drug and device product candidate to treat acute and chronic pain. The drug is being developed to be a non-opioid triple-strength, non-aqueous lidocaine topical system for treatment of acute LBD. Maze Therapeutics’ MZE001 received Orphan Drug Designation from the FDA for Pompe disease. The drug is an oral glycogen synthase (GYS1) inhibitor. Pfizer and BioNTech’s bivalent and Omicron BA.4/BA.5 COVID-19 vaccines for COVID-19 were granted Emergency Use Authorization for people 12 years and older as a single booster dose. Moderna reported the FDA granted EUA for its bivalent COVID-19 vaccine for people 18 years and older as a single booster. Aquestive Therapeutics reported the FDA granted tentative approval for Libervant (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity. Baxter International announced the FDA granted 510(k) clearance for its new Novum IQ syringe infusion pump with Dose IQ Safety Software. Aug. 29 Neuronetics received 510(k) clearance for its D-Tect MT Accessory, which helps doctors by visually reporting the magnitude of finger movements during motor threshold (MT) mapping for treatment of major depressive disorder. Serpex Medical received 510(k) clearance for its Recon Steerable Sheath, a steerable endobronchial tool to enable physicians to access difficult-to-reach areas of the lung. TRACON Pharmaceuticals received the go-ahead for a Phase I/II trial of YH001 in combination with envafolimab and doxorubicin for sarcoma patients, including treatment-naïve patients. It will evaluate patients with the combination of YH001 and envafolimab in patients with the rare sarcoma subtypes of alveolar soft part sarcoma and chondrosarcoma. It will also evaluate YH001, envafolimab and doxorubicin in the more prevalent subtypes of leiomyosarcoma and dedifferentiated liposarcoma. YH001 is an IgG1 antibody against CTLA-4. BrainsWay received 510(k) clearance from the FDA for its Deep TMS H7 Coil for use in treating adults with major depressive disorder and depression including those with comorbid anxiety symptoms (anxious depression). Deep TMS is Deep Transcranial Magnetic Stimulation.

基因疗法抗体孤儿药细胞疗法疫苗

100 项与 Semzuvolimab 相关的药物交易

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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
HIV感染	临床3期	中国	联合生物制药股份有限公司	2020-05-06
HIV感染	临床3期	中国	联亚药业股份有限公司	2020-05-06

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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


NCT02369146 (Pubmed \| Br Dent J)	临床2期	HIV感染	29	UB-421 10 mg/kg	願獵築蓋選蓋範蓋積齋(鹽壓淵繭淵願壓餘簾積) = Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash 獵繭蓋襯餘構製製獵艱 (鬱鑰遞襯壓鹽廠構簾鏇 ) 更多	-	2019-04-18
				UB-421 25 mg/kg