ART-I02(ART-I02) - 药物靶点：IFNAR x IFNβ_在研适应症：类风湿关节炎_专利_临床

概要

基本信息

药物类型

腺相关病毒基因治疗

别名

AAV5.NF-kB.IFN-β、Recombinant AAV type2/5 containing a hIFN-b gene

靶点

IFNAR x IFNβ

作用机制

IFNAR激动剂(干扰素α/β受体复合体激动剂)、IFNβ刺激剂(干扰素-β刺激剂)

治疗领域

免疫系统疾病皮肤和肌肉骨骼疾病

在研适应症

类风湿关节炎

非在研适应症

骨关节炎

原研机构

MeiraGTx Netherlands BV

在研机构

Academic Medical Center University of AmsterdamBiomedical Primate Research Centre

非在研机构

MeiraGTx Netherlands BV

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

2

项与 ART-I02 相关的临床试验

NCT03445715 / Unknown status临床1期

A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Rheumatoid Arthritis

This study will evaluate the safety and tolerability of a single intra-articular administration of ART-I02 (AAV5.NF-kB.IFN-β), a recombinant adeno-associated virus (AAV) type 5 vector in subjects with RA and active arthritis of a wrist.

开始日期2018-01-03

申办/合作机构

MeiraGTx Netherlands BV

NCT02727764 / Unknown status临床1期

A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Arthritis

This study will evaluate the safety and tolerability of a single intra-articular administration of ART-I02 (AAV5.NF-kB.IFN-β), a recombinant adeno-associated virus (AAV) type 2/5 vector in subjects with Rheumatoid Arthritis (RA) or Osteoarthritis (OA) and active arthritis of the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joints.

开始日期2017-04-20

申办/合作机构

MeiraGTx Netherlands BV

[+1]

100 项与 ART-I02 相关的临床结果

登录后查看更多信息

100 项与 ART-I02 相关的转化医学

登录后查看更多信息

100 项与 ART-I02 相关的专利（医药）

登录后查看更多信息

3

项与 ART-I02 相关的文献（医药）

2022-01-01·Osteoarthritis and Cartilage2区 · 医学

Administration of an adeno-associated viral vector expressing interferon-β in patients with inflammatory hand arthritis, results of a phase I/II study

2区 · 医学

Article

作者: Burggraaf, J ; Bevaart, L ; Kamerling, I M C ; Lamers, R J ; Kloppenburg, M ; Nelissen, R G H H ; Klarenbeek, N B ; Navas-Cañete, A ; Meulenberg, J J M ; Ruiterkamp, G ; Huizinga, T W J ; Reijnierse, M ; Vrouwe, J P M

OBJECTIVEInflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-β, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA.METHODSIn this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 10¹²-1.2 × 10¹³ genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-β immune responses were evaluated. A data review committee provided safety recommendations.RESULTSFour patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-β, nor IFN-β antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose.CONCLUSIONSingle IA doses of 0.6 × 10¹² or 1.2 × 10¹² ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation.TRIAL REGISTRATIONNCT02727764.

2015-06-01·Human Gene Therapy Clinical Development3区 · 医学

Safety, Biodistribution, and Efficacy of an AAV-5 Vector Encoding Human Interferon-Beta (ART-I02) Delivered via Intra-Articular Injection in Rhesus Monkeys with Collagen-Induced Arthritis

3区 · 医学

Article

作者: Breedveld, Elia ; Vierboom, Michel P.M. ; Wright, J. Fraser ; Bevaart, Lisette ; Kondova, Ivanela ; Aalbers, Caroline J. ; Hauck, Bernd ; Vervoordeldonk, Margriet J. ; Broekstra, Niels ; Tak, Paul Peter

Preclinical studies to assess biodistribution, safety, and initial efficacy of ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon β (hIFN-β), were performed in a total of 24 rhesus monkeys with collagen-induced arthritis. All monkeys were naïve or showed limited neutralizing antibody (Nab) titers to AAV5 at the start of the study. Animals were injected with a single intra-articular dose of ART-I02 or placebo, consisting of 3.2×10(13) vg (Dose A=maximum feasible dose), 4.58×10(12) vg (Dose B), or placebo in the first affected finger joint, the ipsilateral knee, and ankle joint at the same time point. Animals were monitored for clinical parameters and well-being with a maximum of 4 weeks, with the option that the severity of arthritis could necessitate an earlier time point of sacrifice. No adverse events were noted after injection of ART-I02. No abnormalities were observed after histological evaluation of all organs. At both dose levels, immunohistochemical staining indicated expression of hIFN-β. In animals injected with Dose A, we observed stabilization or a reduction in swelling in the finger joint in which vector was administered. The highest copy numbers of vector DNA were detected in synovial tissue of the injected joint and the draining lymph node of the injected knee. High titers of Nab to rAAV5 were observed at the end of the study. Five monkeys developed an rAAV5-specific T-cell response. Two monkeys developed Nab to hIFN-β. In conclusion, intra-articular injection of ART-I02 was well-tolerated and did not induce adverse events. After administration of Dose A of ART-I02, we observed a beneficial effect on joint swelling, substantiated by decreased histological inflammation and bone erosion scores. A GMP vector for clinical application has been manufactured and is currently being tested in GLP rodent studies, with the aim to move forward to a clinical trial.

PLOS ONE3区 · 综合性期刊

Preclinical Potency and Biodistribution Studies of an AAV 5 Vector Expressing Human Interferon-β (ART-I02) for Local Treatment of Patients with Rheumatoid Arthritis

3区 · 综合性期刊

ArticleOA

作者: de Cortie, Karin ; Aalbers, Caroline J ; Mingozzi, Federico ; Loiler, Scott ; Tak, Paul P ; Vervoordeldonk, Margriet J ; Wright, J Fraser ; Bevaart, Lisette

INTRODUCTIONProof of concept for local gene therapy for the treatment of arthritis with immunomodulatory cytokine interferon beta (IFN-β) has shown promising results in animal models of rheumatoid arthritis (RA). For the treatment of RA patients, we engineered a recombinant adeno-associated serotype 5 vector (rAAV5) encoding human (h)IFN-β under control of a nuclear factor κB promoter (ART-I02).METHODSThe potency of ART-I02 in vitro as well as biodistribution in vivo in arthritic animals was evaluated to characterize the vector prior to clinical application. ART-I02 expression and bioactivity after transduction was evaluated in fibroblast-like synoviocytes (FLS) from different species. Biodistribution of the vector after local injection was assessed in a rat adjuvant arthritis model through qPCR analysis of vector DNA. In vivo imaging was used to investigate transgene expression and kinetics in a mouse collagen induced arthritis model.RESULTSTransduction of RA FLS in vitro with ART-I02 resulted in high expression levels of bioactive hIFN-β. Transduction of FLS from rhesus monkeys, rodents and rabbits with ART-I02 showed high transgene expression, and hIFN-β proved bioactive in FLS from rhesus monkeys. Transgene expression and bioactivity in RA FLS were unaltered in the presence of methotrexate. In vivo, vector biodistribution analysis in rats after intra-articular injection of ART-I02 demonstrated that the majority of vector DNA remained in the joint (>93%). In vivo imaging in mice confirmed local expression of rAAV5 in the knee joint region and demonstrated rapid detectable and sustained expression up until 7 weeks.CONCLUSIONSThese data show that hIFN-β produced by RA FLS transduced with ART-I02 is bioactive and that intra-articular delivery of rAAV5 drives expression of a therapeutic transgene in the joint, with only limited biodistribution of vector DNA to other tissues, supporting progress towards a phase 1 clinical trial for the local treatment of arthritis in patients with RA.

100 项与 ART-I02 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
骨关节炎	药物发现	荷兰	MeiraGTx Netherlands BV	2017-04-20
类风湿关节炎	药物发现	荷兰	MeiraGTx Netherlands BV	2017-04-20

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02727764 (Pubmed \| Osteoarthritis Cartilage) 人工标引	临床1/2期	关节炎	4	ART-I02	(製夢鬱蓋糧遞糧膚顧網) = 範廠範網築廠齋範壓繭顧鏇鹽繭鹽網鹽構製鬱 (壓築觸襯觸簾淵鹽網齋 )	不佳	2021-10-06