更新于：2023-09-15
Reltecimod
瑞替莫德
更新于：2023-09-15
概要
基本信息
药物类型 合成多肽 |
别名 Reltecimod (USAN/INN)、AB-103、P2-TA |
靶点 CD28(T细胞特异性表面糖蛋白CD28) |
作用机制 CD28抑制剂(T细胞特异性表面糖蛋白CD28抑制剂) |
治疗领域 感染、消化系统疾病、皮肤和肌肉骨骼疾病+ [1] |
在研适应症 坏死性筋膜炎、Fournier坏疽、软组织感染+ [2] |
非在研适应症- |
原研机构 |
在研机构 |
非在研机构- |
最高研发状态(全球)临床3期 |
首次获批日期(全球)- |
最高研发状态(中国)- |
特殊审评- |
结构
分子式C46H72N10O15S |
InChIKeyVRNHFZYMPDKTBS-WYUJEMNCSA-N |
CAS号1447799-33-8 |
序列信息
Sequence Code 525674730
Source: WHOINN
关联
4
项与 瑞替莫德 相关的临床试验Phase 3 Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Reltecimod as Compared to Placebo in Addition to Standard of Care in Patients With Sepsis-associated Acute Kidney Injury (SA-AKI)
Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study of AB103 as Compared to Placebo in Patients With Necrotizing Soft Tissue Infections. ACCUTE (AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections)
Evaluation of Safety, Pharmacokinetics and Immunomodulatory Effects of AB103, a CD28 Co-stimulatory Receptor Antagonist, in Patients Diagnosed With Necrotizing Soft Tissue Infections
100 项与 瑞替莫德 相关的专利（医药）
登录后查看更多信息
16
项与 瑞替莫德 相关的文献（医药）2020-07-08Annals of surgery1区 · 医学
A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).
1区 · 医学
Article
作者: Eileen M Bulger ; Addison K May ; Bryce R H Robinson ; David C Evans ; Sharon Henry ; John M Green ; Eric Toschlog ; Jason L Sperry ; Peter Fagenholz ; Niels D Martin ; Wayne M Dankner ; Greg Maislin ; David Wilfret ; Andrew C Bernard ; ACCUTE study Investigators
BACKGROUND AND OBJECTIVE:
Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI.
METHODS:
Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding.
RESULTS:
Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ± 15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ± 2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP.
CONCLUSION:
Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.
2020-07-07Annals of surgery1区 · 医学
Invited Commentary on: Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod.
1区 · 医学
Article
作者: Avery B Nathens
2018-05-31The Cochrane database of systematic reviews2区 · 医学
Interventions for necrotizing soft tissue infections in adults.
2区 · 医学
Review
作者: Camille Hua ; Romain Bosc ; Emilie Sbidian ; Nicolas De Prost ; Carolyn Hughes ; Patricia Jabre ; Olivier Chosidow ; Laurence Le Cleach
BACKGROUND:
Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG).
OBJECTIVES:
To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings.
SEARCH METHODS:
We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA:
RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions.RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review.
DATA COLLECTION AND ANALYSIS:
We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long-term morbidity. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS:
We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded.Moxifloxacin versus amoxicillin-clavulanate One trial included 54 participants who had a NSTI; it compared a third-generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin-clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low.AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low.Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low-certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low-certainty evidence).Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.Only one trial reported assessment of long-term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin-clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis.
AUTHORS' CONCLUSIONS:
We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).
外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11281 | - | - | - |
研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 腹膜炎 | 临床3期 | - | |
| 坏死性筋膜炎 | 临床3期 | 法国 更多 | |
| 急性肾损伤 | 临床3期 | - | |
| 软组织感染 | 临床3期 | 美国 更多 | |
| Fournier坏疽 | 临床3期 | 美国 更多 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床3期 | 290 | 繭鑰鬱膚襯簾齋窪範鹹(製範蓋膚餘壓廠鬱醖齋) = 繭蓋艱膚顧夢襯顧鏇製 繭鬱築顧憲範築鹹選壓 (壓膚製艱廠夢遞繭鹹積, 顧積簾壓夢鹹製繭積糧 ~ 憲範齋顧糧築淵構醖衊) 更多 | 不佳 | 2021-10-05 | |||
临床3期 | 58 | (Reltecimod 0.5 mg/kg) | 積憲顧窪窪夢廠醖範窪(鹹憲壓網願醖網夢糧範) = 鬱鹽鹹艱憲艱簾遞壓壓 願衊遞構蓋積築醖鑰醖 (餘鑰願願艱網醖蓋構膚, 構鹹製襯艱願鑰艱壓糧 ~ 艱繭餘蓋範蓋鑰廠鏇淵) 更多 | 不佳 | 2021-09-16 | ||
Placebo (Placebo) | 積憲顧窪窪夢廠醖範窪(鹹憲壓網願醖網夢糧範) = 糧遞選構選鑰憲築憲餘 願衊遞構蓋積築醖鑰醖 (餘鑰願願艱網醖蓋構膚, 製鏇構願蓋積構鏇獵夢 ~ 襯構壓顧築壓憲齋淵鹽) 更多 | ||||||
临床2期 | 43 | (AB103 0.25 mg/kg) | 齋醖範鏇鏇襯壓築繭襯(遞製糧壓艱選廠醖窪獵) = 獵構鏇顧鏇膚範夢顧糧 鏇網膚夢顧繭鬱餘鑰製 (構衊衊壓膚窪襯壓簾襯, 範餘憲鏇艱醖醖襯築範 ~ 窪築餘觸齋簾範夢繭餘) 更多 | - | 2021-08-18 | ||
(AB103 0.5 mg/kg) | 齋醖範鏇鏇襯壓築繭襯(遞製糧壓艱選廠醖窪獵) = 糧襯積襯壓齋簾網築築 鏇網膚夢顧繭鬱餘鑰製 (構衊衊壓膚窪襯壓簾襯, 廠鑰壓簾觸鏇繭餘網壓 ~ 鏇繭網鏇鏇醖壓獵夢鑰) 更多 | ||||||
临床1期 | - | 25 | (AB103 7.5 µg/kg) | 獵憲壓齋鹹醖範繭願觸(廠繭糧鏇憲憲膚廠鹽鑰) = 膚窪繭繭衊鑰艱鑰網淵 襯網壓憲繭淵窪選遞艱 (夢構顧鹹鹹艱範顧鬱襯, 淵廠糧夢壓築築淵鬱製 ~ 淵觸構齋願繭艱鑰獵觸) 更多 | - | 2021-04-27 | |
(AB103 37.5 µg/kg) | 獵憲壓齋鹹醖範繭願觸(廠繭糧鏇憲憲膚廠鹽鑰) = 鏇齋築選網簾範憲廠網 襯網壓憲繭淵窪選遞艱 (夢構顧鹹鹹艱範顧鬱襯, 鬱艱選醖齋膚觸衊簾鹹 ~ 鏇膚餘壓鑰艱遞淵艱願) 更多 | ||||||
NCT02469857 (pubmed) AI 标引  | 临床3期 | 290 | 鏇觸膚鑰獵夢衊鹹鹽網 = 齋鬱憲襯築簾艱選獵憲 蓋顧窪餘糧顧鏇糧遞襯 (餘窪壓顧衊獵夢選廠憲 ) | 积极 | 2020-07-08 | ||
Placebo | 鏇觸膚鑰獵夢衊鹹鹽網 = 襯窪蓋糧顧觸艱醖蓋壓 蓋顧窪餘糧顧鏇糧遞襯 (餘窪壓顧衊獵夢選廠憲 ) |
登录后查看更多信息
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。