scholarly journals A Nonrandomized Phase 2 Trial of EG-Mirotin, a Novel, First-in-class, Subcutaneously Delivered Peptide Drug for Non-Proliferative Diabetic Retinopathy

Author(s):  
Seunghoon Yoo ◽  
Dae Hyuk You ◽  
Jeongyoon Lee ◽  
H. Christian Hong ◽  
Sung Jin Lee

ABSTRACTBackgroundEG-Mirotin, which includes an active ingredient; EGT022, targeting Non-Proliferative Diabetic Retinopathy (NPDR), the early stage of retinopathy. EG-Mirotin is a drug that is used before capillary damage progresses to an irreversible stage. Safety and efficacy of EG-Mirotin were investigated in subjects with Type 1 or 2 diabetes and NPDR with the degree from moderate to severe.MethodsSubjects (n=10, 20 eyes) satisfying the selection criteria through the screening test were administered EG-Mirotin once a day (3 mg in 1.5 ml of sterile saline) for 5 days, 5 times in total, and were evaluated of the Ischemic index changes and safety. End-of-study (EOS) is performed approximately 8 weeks ± 1 (57 days ± 7) from the first dose.ResultsA total of 4 Treatment Emergent Adverse Events (TEAE) were observed in 2 subjects out of 10 (20.00%) who received the investigational drug. Among them, no subjects were reported experiencing a TEAE related to the investigational drug. All injections were well tolerated (3 mg in 1.5 ml of sterile saline) with no dose-limiting adverse events, deaths, serious adverse events. The overall average percent change in ischemic index at each evaluation point compared to baseline was statistically significant (Greenhouse-Geisser F=9.456, p=0.004 for the main effect of time), and a larger change was observed when the baseline ischemic index value was high (Greenhouse-Geisser F=10.946, p=0.002 for the time*group interaction).ConclusionsEG-Mirotin was well tolerated and found to reverse the ischemia and leakage of capillaries in the retina caused by diabetes.

2020 ◽  
Vol 08 (06) ◽  
pp. E717-E721
Author(s):  
Fadi Hawa ◽  
Zeyad Sako ◽  
Than Nguyen ◽  
Andrew T. Catanzaro ◽  
Eugene Zolotarevsky ◽  
...  

Abstract Background and study aims Endoscopic resection is recommended as initial treatment for early-stage gastric and duodenal neuroendocrine tumors (G-NETs and D-NETs). However, it can cause serious adverse events. We aimed to evaluate the efficacy and safety of the band and slough (BAS) technique as a novel and less aggressive endoscopic therapy for management of such tumors.Four patients, three diagnosed with < 10-mm D-NET and one with 10-mm type I G-NET, were treated with the BAS technique without endoscopic resection. Initial follow-up endoscopy at 3 months was done to assess for residual tumor. Subsequent endoscopic surveillance was performed. After one session of banding, all patients achieved complete remission at 3-month follow-up. No tumor recurrence was detected on repeat biopsy at 12-month surveillance endoscopy. None of the patients developed any adverse events including bleeding or perforation.The BAS technique may prove to be a safe and effective endoscopic therapy for diminutive, non-metastatic type 1 G-NETs and D-NETs. Studies of larger scale and longer follow-up periods are needed to corroborate these findings.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rong Tao ◽  
Lei Fan ◽  
Yongping Song ◽  
Yu Hu ◽  
Wei Zhang ◽  
...  

AbstractThis study (ORIENT-4) aimed to assess the efficacy and safety of sintilimab, a humanized anti-PD-1 antibody, in patients with relapsed/refractory extranodal NK/T cell lymphoma (r/r ENKTL). ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial (NCT03228836). Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was the objective response rate (ORR) based on Lugano 2014 criteria. Twenty-eight patients with r/r ENKTL were enrolled from August 31, 2017 to February 7, 2018. Twenty-one patients (75.0%, 95% CI: 55.1–89.3%) achieved an objective response. With a median follow-up of 30.4 months, the median overall survival (OS) was not reached. The 24-month OS rate was 78.6% (95% CI, 58.4–89.8%). Most treatment-related adverse events (TRAEs) were grade 1–2 (71.4%), and the most common TRAE was decreased lymphocyte count (42.9%). Serious adverse events (SAEs) occurred in 7 (25.0%) patients, and no patient died of adverse events. Sintilimab is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.


Blood ◽  
2021 ◽  
Author(s):  
Petra Langerbeins ◽  
Can Zhang ◽  
Sandra Robrecht ◽  
Paula Cramer ◽  
Moritz Fürstenau ◽  
...  

Observation is the current standard of care for patients with early stage asymptomatic chronic lymphocytic leukemia (CLL), as chemotherapy-based interventions have failed to prolong survival. We hypothesized that early intervention with ibrutinib would be well tolerated and lead to superior disease control in a subgroup of early stage patients with CLL. The phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (N=182) or placebo (N=181) at a dose of 420 mg daily. At a median follow up of 31 months the study met its primary endpoint by significantly improving event-free survival in the ibrutinib group (median, not reached vs. 47.8 months; hazard ratio=0.25; 95% confidence interval=0.14-0.43, P&lt;0.0001). Compared to placebo, ibrutinib did not increase overall toxicity, yielding similar incidence and severity of adverse events. The most common serious adverse events were atrial fibrillation, pneumonia and rash in the ibrutinib group, and basal cell carcinoma, pneumonia and myocardial infarction in the placebo group. Ibrutinib-associated risk for bleeding (33.5%) was decreased by prohibiting use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug-drug interactions. Taken together, ibrutinib confirms efficacy in CLL patients at early stage with increased risk of progression. However, the results do not justify to change the current standard of 'watch and wait'. The trial is registered at clinicaltrials.gov as NCT02863718.


2020 ◽  
Vol 3 (2) ◽  
pp. 51-57
Author(s):  
Defayudina Dafilianty Rosataria ◽  
Ramzi Amin

ABSTRACT Introduction : In general, diabetic retinopathy is classified into early stage, namely non proliferative diabetic retinopathy (NPDR), and advanced stage, proliferative diabetic retinopathy (PDR). Diabetic macular edema is the most common cause of visual impairment in cases of early stage or NPDR. Purpose : To describe Diabetic Macular Edema (DME) with intravitreal injection of anti-VEGF as a treatment. Case report : 43 old female, came with chief complaint of blurred vision on her right eye since six months ago. Blurring is felt slowly. Patient has a history of uncontrolled diabetes since 10 years and a history of hypercholesterolemia since 1 year ago. visual acuity of the right eye is 4/60. On posterior segment examination, neovascularization of the papilla was found. Decreased foveal reflex (+), hard exudates (+) within 500 µm from the central macula. Microaneurism (+), dot hemorrhage (+), blot (+) in 4 quadrants, hard exudates (+) in 2 quadrants in her right eye. The patient was planned for intravitreal injection of anti-VEGF on her right eye. Conclusion : Intravitreal injection of anti-VEGF can improve visual acuity and reduce exudate and hemorrhage in retina from ophthalmoscope and fundus photography examination. In addition, the investigation with OCT was found to improve with reduced macular thickness.  


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 251-251
Author(s):  
Suthat Fucharoen ◽  
Nattawara Chaneiam ◽  
Beer Poramin Patthamalai ◽  
Susan P Perrine

Abstract Abstract 251 Beta thalassemia intermedia (BTI) syndromes are characterized by globin chain imbalance, ineffective erythropoiesis, hemolytic anemia, and have no therapeutic approved for the underlying pathology. Higher fetal globin (HbF) expression can compensate for beta globin deficiency, reduce globin chain imbalance, and ameliorate phenotype within the same genotypes. HQK-1001 (HemaQuest Pharmaceuticals, San Diego, CA) is an orally bioavailable, non-cytotoxic, short-chain fatty acid derivative which induces fetal globin expression in multiple experimental models. In thalassemic erythroid progenitors in vitro, HQK-1001 prolongs STAT-5 phosphorylation and increases expression of the pro-survival protein Bcl-xL. In a Phase I/II dose-escalation trial in BTI, HQK-1001 administered at 10, 20, 30, and 40 mg/kg/day for 8 weeks was well–tolerated, demonstrated a t½ of 9–11 hours, and treatment resulted in an increase in HbF and total hemoglobin (Hgb), with best results observed at 20 mg/kg. This open-label Phase 2 trial evaluated HQK-1001 administered orally at 20 mg/kg once daily for 26 weeks in adult patients with HbE-β0 thalassemia (NCT01609595). Ten subjects were enrolled, ages 20–36 years, including 7/10 female and 5/10 splenectomized subjects. The beta globin molecular mutations of the subjects, in addition to Codon 26 (G-A), included Codon 41/42 (-TTCT), Codon 17 (A-T), Codon 110 (T-C), and IVS I-I (G-T). At the time of this analysis, 9 of 10 subjects have completed at least 20 weeks of dosing. HbF has increased in all subjects above baseline levels by a mean of 10% (range 4.3% to 20.9%) and total HbF has increased by a mean of 1.07 g/dL, (range 0.52–2.38 g/dL, with positive changes in total HbF observed in 9/10 subjects. Total Hgb has increased by >0.5 g/dL above baseline (mean of 1.27 g/dL, range 0.7 to 2.2 g/dL) in 3 subjects after 3 to 5 months of dosing. Treatment was well-tolerated. There have been no severe drug-related adverse events, no serious adverse events, and no clinically relevant laboratory abnormalities. One subject developed transient proteinuria and edema without changes in renal function 3 weeks following an episode of pharyngitis. This ongoing trial demonstrates consistent induction of fetal globin expression by HQK-1001 at a well-tolerated dose level in subjects with HbE-beta thalassemia. Disclosures: Fucharoen: HemaQuest Pharmaceuticals: Research Funding. Perrine:HemaQuest Pharmaceuticals: Equity Ownership, Patents & Royalties.


2017 ◽  
Vol 35 (29) ◽  
pp. 3298-3305 ◽  
Author(s):  
Katherine E. Reeder-Hayes ◽  
Anne Marie Meyer ◽  
Sharon Peacock Hinton ◽  
Ke Meng ◽  
Lisa A. Carey ◽  
...  

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2–positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score–matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer–specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab. We did not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate.


2018 ◽  
Vol 102 (10) ◽  
pp. 1351-1357 ◽  
Author(s):  
Yoshihiro Takamura ◽  
Masahiko Shimura ◽  
Takashi Katome ◽  
Hideaki Someya ◽  
Masahiko Sugimoto ◽  
...  

Background/AimsTo investigate whether intravitreal injection of triamcinolone acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR).MethodsThis prospective, multicentre, randomised study conducted at seven sites in Japan enrolled patients diagnosed as having VH following PDR. Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA at the end of the surgery. Anterior flare intensity (AFI), central retinal thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery and compared.ResultsNumber of patients who completed 6 months of follow-up was 40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week (P=0.019) and 1 month (P=0.037). There were no significant differences in CRT, BCVA and IOP between the groups through the observational periods. In the cases with macular oedema >350 µm of CRT at 3 days, CRT was significantly lower in the IVTA+VIT group than in the VIT group at 1 month (P=0.041).ConclusionsIVTA combined with vitrectomy and cataract surgery contributed to inhibit the postoperative inflammation in patients with VH due to PDR. The effect of IVTA in the reduction of diabetic macular oedema may be limited to the early stage after surgery.Trial registration numberUMIN000020376, Post-results.


2019 ◽  
Author(s):  
Dandan Zhu ◽  
Xun Liu

Abstract Background To analyze the optical coherence tomography angiography(OCTA) and microperimetry features in diabetic patients without diabetic retinopathy(NDR group) and patients with early stage of non-proliferative diabetic retinopathy(NPDR group). Methods This was a cross-sectional study including 24 eyes of the NDR group, 24 eyes of the NPDR group, and 24 eyes of healthy volunteers(control group). OCTA was used to measure foveal avascular zone(FAZ), vessel flow density of superficial capillary plexus(SCP) and deep capillary plexus(DCP) in the macular area(3×3mm). The latest version of microperimeter, MP-3, was used to quantitate retinal light sensitivity and fixation stability in the central 10° of the macular region. Results The NPDR group had a larger FAZ area, reduced vessel flow densities of both SCP and DCP, deceased retinal sensitivity and less stable fixation compared with the control group. Statistical differences were only found in the FAZ area, vessel flow density of DCP and retinal sensitivity between the NDR and the NDPR group. Conclusions The FAZ enlargement, vessel flow density decrease and retinal sensitivity reduction may be morphological and functional indicators of progression of diabetic retinopathy. Microvascular alterations in deep capillary plexus may precede superficial capillary alterations in diabetic retinopathy.


2019 ◽  
Vol 9 (2) ◽  
pp. 274-283
Author(s):  
Xiaobo Lai ◽  
LV Lili ◽  
Zihe Huang

It is desirable to diagnose diabetic retinopathy at an early stage for developing a suitable treatment plan to prevent the condition from deteriorating. To provide an immediate diagnosis of the retina, various methods have been investigated to realize a time and cost effective classification of the fundus images. However, most diabetic retinopathy automated identification methods are structural based analysis. Moreover, Asian fundus images have larger optic disc and thicker retinal vessels compared with Caucasians. Hence, we explore a machine learning approach to the extraction of texture features for classification and the feasibility of this approach using texture parameters to complement current algorithms. Normal retina, non-proliferative diabetic retinopathy and proliferative diabetic retinopathy are identified in this paper. The first step is achieved with three groups of texture features such as gray level co-occurrence matric texture features, different statistical features and run length matrix texture features extracted. In the second step, these features are fed into an optimized random forest classifier for automatic classification. We test our system on two databases (D1 and D2) consisting of 432 and 579 fundus images from a diabetic retinopathy screening program consisting of Asians. The diabetic retinopathy is successfully diagnosed with sensitivity is 0.936 ± 0.019 for D1 and 0.941 ± 0.016 for D2, specificity is 0.917 ± 0.011 for D1 and 0.918 ± 0.011 for D2, positive predictive value is 0.924 ± 0.013 for D1 and 0.939 ± 0.012 for D2, when training on the same institutions, respectively.


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