A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Subjects With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor

Phase 2 study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of KPL-404 in subjects with moderate to severe Rheumatoid Arthritis.

开始日期2021-12-14

申办/合作机构

Kiniksa Pharmaceuticals Ltd.

NCT04497662 / Completed临床1期

A Phase 1 First-in-human Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous and Subcutaneous Doses of KPL-404 in Healthy Subjects

Phase 1, randomized, double-blind, placebo-controlled first-in-human study to investigate the safety, tolerability, PK and PD properties of single ascending intravenous (IV) and subcutaneous (SC) doses of KPL-404 in healthy subjects

开始日期2019-10-22

申办/合作机构

Kiniksa Pharmaceuticals Ltd.

100 项与 Abiprubart 相关的临床结果

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100 项与 Abiprubart 相关的转化医学

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项与 Abiprubart 相关的文献（医药）

2023-12-01·The Journal of pharmacology and experimental therapeutics

First-in-Human Phase 1 Randomized Trial with the Anti-CD40 Monoclonal Antibody KPL-404: Safety, Tolerability, Receptor Occupancy, and Suppression of T-Cell–Dependent Antibody Response

Article

作者: Ziemniak, John ; Samant, Manoj ; Paolini, John F

Blockade of the cluster of differentiation 40 (CD40)-CD40L interaction has potential for treating autoimmune diseases and preventing graft rejection. This first-in-human, randomized, double-blind, placebo-controlled study (NCT04497662) evaluated safety, pharmacokinetics, receptor occupancy, and pharmacodynamics of the humanized anti-CD40 monoclonal antibody KPL-404. Healthy volunteers were randomized to one of two single-ascending-dose groups: single intravenous KPL-404 dose 0.03, 0.3, 1, 3, or 10 mg/kg or single subcutaneous KPL-404 dose 1 or 5 mg/kg. There were no dose-limiting or dose-related safety findings. Nonlinear dose-dependent changes in various pharmacokinetic parameters were identified following the range of intravenous doses. At the 10 mg/kg intravenous dose level, the t_1/2 was approximately 7 days, and full receptor occupancy was observed through Day 71, with complete suppression of T-cell-dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) challenge on Day 1 and rechallenge on Day 29 through Day 57. With KPL-404 5 mg/kg subcutaneously, full receptor occupancy was observed through Day 43, with complete suppression of TDAR through at least Day 29. Antidrug antibodies to KPL-404 were suppressed for 57 days with 10 mg/kg intravenously and for 50 days with 5 mg/kg subcutaneously, further confirming prolonged target engagement and pharmacodynamics. These findings support continued investigation of KPL-404 intravenous and subcutaneous administration in a broad range of indications. SIGNIFICANCE STATEMENT: This first-in-human clinical trial of KPL-404, a fully humanized IgG4 monoclonal antibody, was designed with two independent (by route of administration) placebo-controlled single-ascending-dose-level groups, one with four intravenous single-dose cohorts and another with two subcutaneous single-dose cohorts. The pharmacokinetic profile, duration of full CD40 receptor occupancy, and magnitude and duration of memory immune response suppression observed confirm pharmacodynamic activity regardless of administration route. These data provide evidence that chronic KPL-404 dosing regimens (intravenous or subcutaneous) could be practical.

2022-04-01·The Journal of pharmacology and experimental therapeutics3区 · 医学

Preclinical Immunopharmacologic Assessment of KPL-404, a Novel, Humanized, Non-Depleting Antagonistic Anti-CD40 Monoclonal Antibody

3区 · 医学

Article

作者: Muralidharan, Sujatha ; Garron, Tracy ; Njenga, Moses ; Paolini, John F ; Bondensgaard, Kent

The CD40/CD40L pathway plays a major role in multiple inflammatory processes involving different immune and stromal cells. Abnormal activation of this pathway has been implicated in pathogenesis of complex autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, Graves' disease, and Sjogren's Syndrome. We completed in vitro and in vivo preclinical characterization of KPL-404, a novel humanized anti-CD40 IgG4 monoclonal antibody, to demonstrate its potency, efficacy, and pharmacokinetic profile; safety was also assessed. In vitro, KPL-404 bound recombinant human and cynomolgus monkey CD40 with comparable affinity in the nanomolar range. KPL-404 binding to cell surface CD40 did not induce antibody- or complement-mediated cytotoxicity of CD40-expressing cells. Pharmacological antagonistic activity of KPL-404 was demonstrated in vitro by inhibition of CD40-mediated downstream NF-kB activation. In the in vivo study with cynomolgus monkeys, KPL-404, administered intravenously as a single dose (10 mg/kg) or two monthly doses of 1 or 5 mg/kg, did not elicit observable safety findings, including thrombocytopenia over 8 weeks. KPL-404 engaged CD40 expressed on peripheral B cells for 2 and 4 weeks after a single administration of 5 or 10 mg/kg IV, respectively, without depletion of peripheral B cells. At 5 mg/kg IV, KPL-404 blocked both primary and secondary responses to T-cell dependent antibody responses to test antigens, KLH, and tetanus toxoid. These data illustrated the relationship between KPL-404 serum concentration and pharmacodynamic effects of CD40-targeting in circulation and in lymphoid tissues. These data support clinical development of KPL-404 in autoimmune diseases. SIGNIFICANCE STATEMENT: We aimed to develop a potent and efficacious CD40 antagonist. In vitro and in vivo findings show that KPL-404 blocks the anti-CD40 antibody that potently inhibits primary and secondary antibody responses at pharmacologically relevant concentrations, has a favorable pharmacokinetic profile, and does not deplete B cells by antibody-dependent cellular cytotoxicity or apoptosis ("nondepleting"). These findings support clinical development of KPL-404 as a potential therapeutic in autoimmune diseases.

2021-12-01·Arthritis research & therapy

Correction to: Anti-CD40 antibody KPL-404 inhibits T cell-mediated activation of B cells from healthy donors and autoimmune patients

作者: Giltiay, Natalia V ; Marken, John ; Muralidharan, Sujatha

An amendment to this paper has been published and can be accessed via the original article.

项与 Abiprubart 相关的新闻（医药）

2024-06-24

·GlobeNewswire-Health Care

Kiniksa Pharmaceuticals Partners with NHL Hall-of-Famer Henrik Lundqvist to Raise Awareness of Recurrent Pericarditis

– Campaign to elevate experiences from the recurrent pericarditis community and provide resources to patients and caregivers – HAMILTON, Bermuda, June 24, 2024 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a commercial-stage biopharmaceutical company with a pipeline of immune-modulating assets designed to target a spectrum of cardiovascular and autoimmune diseases, today announced a partnership with National Hockey League (NHL) Hall-of-Famer, Henrik Lundqvist, to raise awareness in support of patients suffering from recurrent pericarditis. Lundqvist has faced the challenges of living with this painful and debilitating chronic autoinflammatory cardiovascular disease. The campaign will kick off in September of this year. Pericarditis is marked by a profound inflammation of the pericardial tissue in the multi-layered sac that surrounds the heart. The associated sharp chest pain frequently requires urgent care and hospitalization, and patients often believe they are having a heart attack. Patients experiencing recurrent pericarditis flares suffer wide-ranging effects on quality of life, physical activity, and overall well-being. “Despite the significant impact of recurrent pericarditis on patients’ lives, the limited understanding of the disease often results in delayed diagnosis and treatment,” said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. “We are honored to collaborate with Henrik Lundqvist to raise awareness of the realities of suffering from recurrent pericarditis. We believe this collaboration will help educate and inspire individuals to take proactive steps to access appropriate medical care early on to prevent future flares.” For more information on recurrent pericarditis, visit whatispericarditis.com. To learn about the first and only U.S. Food and Drug Administration-approved therapy for recurrent pericarditis, visit arcalyst.com. About Recurrent PericarditisRecurrent pericarditis is a painful and debilitating chronic autoinflammatory cardiovascular disease marked by inflammation of the pericardium and is often associated with changes in electrical conduction and sometimes buildup of fluid around the heart, called pericardial effusion. Recurrent pericarditis symptoms have an impact on quality of life, limit physical activities, and lead to frequent emergency department visits and hospitalizations. Data show that approximately 40,000 patients in the U.S. seek and receive treatment for recurrent pericarditis each year. Of that group, approximately 14,000 patients experience two or more recurrences due to persistent underlying disease or inadequate response to conventional therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids. About KiniksaKiniksa is a commercial-stage biopharmaceutical company focused on discovering, acquiring, developing, and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s immune-modulating assets, ARCALYST®, abiprubart, and mavrilimumab, are based on strong biologic rationale or validated mechanisms, target a spectrum of underserved cardiovascular and autoimmune conditions, and offer the potential for differentiation. For more information, please visit www.kiniksa.com. IMPORTANT SAFETY INFORMATION ABOUT ARCALYST ARCALYST may affect your immune system and can lower the ability of your immune system to fight infections. Serious infections, including life-threatening infections and death, have happened in patients taking ARCALYST. If you have any signs of an infection, call your doctor right away. Treatment with ARCALYST should be stopped if you get a serious infection. You should not begin treatment with ARCALYST if you have an infection or have infections that keep coming back (chronic infection).While taking ARCALYST, do not take other medicines that block interleukin-1, such as Kineret® (anakinra), or medicines that block tumor necrosis factor, such as Enbrel® (etanercept), Humira® (adalimumab), or Remicade® (infliximab), as this may increase your risk of getting a serious infection.Talk with your doctor about your vaccine history. Ask your doctor whether you should receive any vaccines before you begin treatment with ARCALYST.Medicines that affect the immune system may increase the risk of getting cancer.Stop taking ARCALYST and call your doctor or get emergency care right away if you have any symptoms of an allergic reaction.Your doctor will do blood tests to check for changes in your blood cholesterol and triglycerides.Common side effects include injection-site reactions (which may include pain, redness, swelling, itching, bruising, lumps, inflammation, skin rash, blisters, warmth, and bleeding at the injection site), upper respiratory tract infections, joint and muscle aches, rash, ear infection, sore throat, and runny nose. For more information about ARCALYST, talk to your doctor and see the Product Information. Forward-Looking StatementsThis press release contains forward-looking statements. In some cases, you can identify forward- looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: the timing of the campaign, our belief that our collaboration will help educate and inspire individuals to take proactive steps to access appropriate medical care early on to prevent future flares and our belief that all of our product candidates offer the potential for differentiation. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our and our partners’ achievements to be materially different from those expressed or implied by the forward-looking statements. These and other important factors discussed in our filings with the U.S. Securities and Exchange Commission, including under the caption “Risk Factors” contained therein, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. Except as required by law, we disclaim any intention or obligation to update or revise any forward-looking statements. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Every Second Counts! ® Kiniksa Investor and Media ContactRachel Frank(339) 970-9437rfrank@kiniksa.com

疫苗

2024-06-17

·GlobeNewswire-Health Care

Kiniksa Pharmaceuticals Sponsors American Heart Association’s Addressing Recurrent Pericarditis Initiative

– Initiative aimed at improving access and outcomes for patients with recurrent pericarditis – – American Heart Association to work with champions at 15 healthcare sites to implement initiative activities and improve care quality – HAMILTON, Bermuda, June 17, 2024 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a commercial-stage biopharmaceutical company with a pipeline of immune-modulating assets designed to target a spectrum of cardiovascular and autoimmune diseases, today announced its sponsorship of the American Heart Association’s new Addressing Recurrent Pericarditis initiative, a multi-faceted effort to improve quality of care through identification, dissemination, and implementation of best practices for the diagnosis and management of recurrent pericarditis. “We are proud to sponsor the American Heart Association’s Addressing Recurrent Pericarditis initiative. Recurrent pericarditis is a rare, chronic, flaring disease, in which patients are frequently misdiagnosed or undertreated due to a lack of access to expert care. In addition to elevating awareness and knowledge around recurrent pericarditis, this initiative will also help strengthen overall care by working to improve processes for diagnosing, referring, and treating patients,” said John F. Paolini, M.D., Ph.D., FACC, Chief Medical Officer of Kiniksa. “Furthermore, this initiative will facilitate knowledge-sharing across a collaborative network of healthcare providers, with the objective of establishing a clear model to streamline patient access to expert care and improved outcomes nationwide.” Through the Addressing Recurrent Pericarditis initiative, the American Heart Association will establish a learning collaborative of champions at fifteen healthcare sites for recurrent pericarditis care. These champions will analyze patient identification and referral pathways, seeking to identify gaps and pragmatic solutions. The ultimate goal of the initiative is to improve outcomes and quality of life for recurrent pericarditis patients by disseminating best practices through national education, model sharing, abstract development, and patient- and physician-targeted podcasts and webinars. “Recurrent pericarditis symptoms can have significant impact on emotional health and quality of life, but they often go undiagnosed and untreated,” said Mariell Jessup, M.D., FAHA, Chief Science and Medical Officer of the American Heart Association. “This new initiative will share insights and best practices nationally to improve identification and treatment for patients with this disease.” Participating sites in the learning collaborative include: Ascension St. Thomas Heart (Nashville, Tennessee)Bluhm Cardiovascular Institute, Northwestern Medicine (Chicago, Illinois)Brigham & Women’s Hospital (Boston, Massachusetts)Cleveland Clinic (Cleveland, Ohio)Houston Medical Hospital (Houston, Texas)Knight Cardiovascular Institute Cardiology Clinic, Oregon Health & Science University (Portland, Oregon)Massachusetts General Hospital (Boston, Massachusetts)Mayo Clinic – Rochester (Rochester, Minnesota)My Cardiologist/CVAUSA (Miami, Florida)New York University Grossman School of Medicine (New York, New York)Pacific Heart Institute (Santa Monica, California)The Regents of the University of California Irvine (Irvine, California)University of Michigan (Ann Arbor, Michigan)University of Utah Hospital (Salt Lake City, Utah)University of Virginia (Charlottesville, Virginia) About Recurrent PericarditisRecurrent pericarditis is a painful and debilitating chronic autoinflammatory cardiovascular disease marked by inflammation of the pericardium and is often associated with changes in electrical conduction and sometimes buildup of fluid around the heart, called pericardial effusion. Recurrent pericarditis symptoms have an impact on quality of life, limit physical activities, and lead to frequent emergency department visits and hospitalizations. Data shows that approximately 40,000 patients in the U.S. seek and receive treatment for recurrent pericarditis each year. Of that group, approximately 14,000 patients experience two or more recurrences due to persistent underlying disease or inadequate response to conventional therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids. About KiniksaKiniksa is a commercial-stage biopharmaceutical company focused on discovering, acquiring, developing, and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s immune-modulating assets, ARCALYST, abiprubart, and mavrilimumab, are based on strong biologic rationale or validated mechanisms, target a spectrum of underserved cardiovascular and autoimmune conditions, and offer the potential for differentiation. For more information, please visit www.kiniksa.com. Forward-Looking StatementsThis press release contains forward-looking statements. In some cases, you can identify forward- looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: the ultimate number of healthcare sites that will participate in the learning collaborative; our belief that the Addressing Recurrent Pericarditis initiative will (a) improve quality of care through identification, dissemination and implementation of best practices for the diagnosis and management of recurrent pericarditis, (b) elevate awareness and knowledge around recurrent pericarditis, (c) strengthen overall care by working to improve processes for diagnosing, referring and treating patients, and (d) facilitate knowledge-sharing across a collaborative network of healthcare providers to streamline patient access to expert care and improve outcomes nationwide; that the healthcare champions participating in the Addressing Recurrent Pericarditis initiative will analyze patient identification and referral pathways, seeking to identify gaps and pragmatic solutions with the ultimate goal of improving outcomes, quality of life, identification and treatment for recurrent pericarditis patients by disseminating insights and best practices; and our belief that all of our product candidates offer the potential for differentiation. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our and our partners’ achievements to be materially different from those expressed or implied by the forward-looking statements. These and other important factors discussed in our filings with the U.S. Securities and Exchange Commission, including under the caption “Risk Factors” contained therein, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. Except as required by law, we disclaim any intention or obligation to update or revise any forward-looking statements. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Every Second Counts! ® Kiniksa Investor and Media ContactRachel Frank(339) 970-9437rfrank@kiniksa.com

AHA会议

2024-05-07

·GlobeNewswire-Health Care

Kiniksa Pharmaceuticals to Present at Bank of America Securities 2024 Health Care Conference

HAMILTON, Bermuda, May 07, 2024 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) today announced that management will participate in a fireside chat at the Bank of America Securities 2024 Healthcare Conference on Tuesday, May 14, 2024 at 10:40 a.m. Pacific Time (1:40 p.m. Eastern Time). A live webcast of Kiniksa’s presentation will be accessible through the Investors & Media section of the company’s website at www.kiniksa.com. A replay of the event will also be available on Kiniksa’s website within approximately 48 hours after the event. About KiniksaKiniksa is a commercial-stage biopharmaceutical company focused on discovering, acquiring, developing, and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s immune-modulating assets, ARCALYST®, abiprubart, and mavrilimumab, are based on strong biologic rationale or validated mechanisms, target a spectrum of underserved cardiovascular and autoimmune conditions, and offer the potential for differentiation. For more information, please visit www.kiniksa.com. ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. Every Second Counts! ®Kiniksa Investor and Media ContactRachel Frank(339) 970-9437rfrank@kiniksa.com

100 项与 Abiprubart 相关的药物交易

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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
类风湿关节炎	临床2期	美国	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	保加利亚	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	捷克	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	格鲁吉亚	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	匈牙利	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	波兰	Kiniksa Pharmaceuticals Ltd.	2021-12-14
类风湿关节炎	临床2期	南非	Kiniksa Pharmaceuticals Ltd.	2021-12-14

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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


GlobeNewswire 人工标引	临床2期	类风湿关节炎	51	Abiprubart (Cohort 4:400 mg SC monthly dose group)	窪憲鑰糧醖齋築願衊範(餘獵鬱鑰壓醖簾醖築遞) = 鹽製鑰顧積艱獵夢鑰廠願鏇襯構憲範築獵窪簾 (願觸繭積艱製艱鬱鹹蓋, -2.54 ~ -1.21)	积极	2024-04-02
				Placebo	窪憲鑰糧醖齋築願衊範(餘獵鬱鑰壓醖簾醖築遞) = 繭窪壓網餘構簾窪構範願鏇襯構憲範築獵窪簾 (願觸繭積艱製艱鬱鹹蓋, -1.98 ~ -0.62)
GlobeNewswire 人工标引	临床2期	类风湿关节炎	129	Abiprubart (pooled group)	夢遞鏇鹽鏇簾範艱鏇餘(範鹹積廠艱遞願壓遞簾) = 膚膚鹹餘齋鏇獵淵遞構繭齋糧鹹觸鏇築鹹淵獵 (鏇顧簾糧願積鏇衊壓積, -2.34 ~ -1.74)	积极	2024-04-02
				Placebo	夢遞鏇鹽鏇簾範艱鏇餘(範鹹積廠艱遞願壓遞簾) = 襯鏇艱網遞醖廠衊醖簾繭齋糧鹹觸鏇築鹹淵獵 (鏇顧簾糧願積鏇衊壓積, -1.88 ~ -1.16)
GlobeNewswire 人工标引	临床2期	类风湿关节炎	-	Abiprubart (Cohort 1)	-	积极	2024-04-02
				Abiprubart (Cohort 2)
Biospace 人工标引	临床2期	类风湿关节炎 Rheumatoid Factor	-	Abiprubart 2 mg/kg SC biweekly dosing (Cohort 1)	餘積衊淵艱膚繭鏇餘壓(鹽選選鏇遞醖鹹艱獵製) = 鏇願範廠繭鑰製簾鏇鬱糧蓋廠膚齋餘觸醖廠淵 (簾鹹願製選膚獵醖衊觸 ) 更多	积极	2024-01-04
				Abiprubart 5 mg/kg SC biweekly dosing (Cohort 2)	餘積衊淵艱膚繭鏇餘壓(鹽選選鏇遞醖鹹艱獵製) = 衊顧蓋膚鏇構鬱膚衊鏇糧蓋廠膚齋餘觸醖廠淵 (簾鹹願製選膚獵醖衊觸 ) 更多