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Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing an anchored RBD: A randomized, observer-blind phase 1 study.
Akahata, W, Sekida, T, Nogimori, T, Ode, H, Tamura, T, Kono, K, Kazami, Y, Washizaki, A, Masuta, Y, Suzuki, R, et al
Cell reports. Medicine. 2023;(8):101134
Abstract
VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. A phase 1 study of VLPCOV-01 is conducted (jRCT2051210164). Participants who completed two doses of the BNT162b2 mRNA vaccine previously are randomized to receive one intramuscular vaccination of 0.3, 1.0, or 3.0 μg VLPCOV-01, 30 μg BNT162b2, or placebo. No serious adverse events have been reported. VLPCOV-01 induces robust immunoglobulin G (IgG) titers against the RBD protein that are maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5,037 (95% confidence interval [CI] 1,272-19,940) at 0.3 μg to 12,873 (95% CI 937-17,686) at 3 μg compared with 3,166 (95% CI 1,619-6,191) with 30 μg BNT162b2. Neutralizing antibody titers against all variants of SARS-CoV-2 tested are induced. VLPCOV-01 is immunogenic following low-dose administration. These findings support the potential for saRNA as a vaccine platform.
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Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial.
Nakamura, J, Hikichi, T, Watanabe, K, Hashimoto, M, Kato, T, Takagi, T, Suzuki, R, Sugimoto, M, Takasumi, M, Sato, Y, et al
Digestion. 2021;(5):753-759
Abstract
INTRODUCTION Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD. METHODS A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1-10 points), adverse events, and rate of ulcer healing 8 weeks after ESD. RESULTS A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group. CONCLUSION SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.
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Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study.
Takeshita, A, Asou, N, Atsuta, Y, Sakura, T, Ueda, Y, Sawa, M, Dobashi, N, Taniguchi, Y, Suzuki, R, Nakagawa, M, et al
Leukemia. 2019;(2):358-370
Abstract
Between April 2004 and December 2010, we conducted a prospective randomized controlled study comparing tamibarotene with all-trans retinoic acid (ATRA) in the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL), and here report the final results of this study with a median follow-up of 7.3 years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%) achieved complete remission (CR). After completion of three courses of consolidation chemotherapy, 269 patients in molecular remission underwent maintenance randomization, 135 to ATRA (45 mg/m2 daily), and 134 to tamibarotene (6 mg/m2 daily) for 14 days every 3 months for 2 years. The primary endpoint was relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in the tamibarotene arm (p = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference was prominent in high-risk patients with initial leukocytes ≥ 10.0 × 109/L (62% vs. 89%; p = 0.034). Tamibarotene was significantly superior to ATRA by decreasing relapse in high-risk patients. Overall survival after randomization did not differ (96% vs. 97%; p = 0.520). Secondary hematopoietic disorders developed in nine patients, secondary malignancies in 11, and grade 3 or more late cardiac comorbidities in three. These late complications did not differ between the two arms.
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Effect of short-term treatment with sitagliptin or glibenclamide on daily glucose fluctuation in drug-naïve Japanese patients with type 2 diabetes mellitus.
Suzuki, R, Eiki, JI, Moritoyo, T, Furihata, K, Wakana, A, Ohta, Y, Tokita, S, Kadowaki, T
Diabetes, obesity & metabolism. 2018;(9):2274-2281
Abstract
AIMS: To compare the effect of a dipeptidyl peptidase-4 inhibitor (DPP4-i) and a sulfonylurea (SU) on daily glucose fluctuation in drug-naïve Japanese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS A total of 53 drug-naïve Japanese patients with T2DM (HbA1c, 7.0%-9.0%; fasting plasma glucose, 6.1 mmol/L or higher) were randomly assigned to either sitagliptin 50 mg qd or glibenclamide 2.5 mg per day (given in divided doses) in a 1:1 ratio. A continuous glucose monitoring (CGM) device was used to obtain 24-hour glucose profiles for each patient at baseline and at Week 2. The primary study endpoint was change from baseline in mean amplitude of glucose excursion (MAGE) during a 24-hour period. A key secondary endpoint was change from baseline in the standard deviation (SD) of 24-hour glucose levels. RESULTS After 2 weeks of treatment, a numerically greater reduction in MAGE from baseline was observed in the sitagliptin group compared with the glibenclamide group, but the between-treatment difference was not statistically significant (LS mean difference [95% CI]: -0.48 mmol/L [-1.31, 0.34]; P = .245). However, a significantly greater reduction in the change from baseline in SD was observed in the sitagliptin group compared with the glibenclamide group (LS mean difference [95% CI]: -0.33 mmol/L [-0.62, -0.03]; P = .029). CONCLUSIONS This study suggests that the DPP4 inhibitor sitagliptin has a greater ability to reduce daily glucose fluctuation than the SU glibenclamide in drug-naïve Japanese patients with T2DM. ClinicalTrials.gov: NCT02318693.
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Factors Associated with Intima-Media Complex Thickness of the Common Carotid Artery in Japanese Noncardioembolic Stroke Patients with Hyperlipidemia: The J-STARS Echo Study.
Wada, S, Koga, M, Toyoda, K, Minematsu, K, Yasaka, M, Nagai, Y, Aoki, S, Nezu, T, Hosomi, N, Kagimura, T, et al
Journal of atherosclerosis and thrombosis. 2018;(4):359-373
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Abstract
AIMS: There may be ethnic differences in carotid atherosclerosis and its contributing factors between Asian and other populations. The purpose of this study was to examine intima-media complex thickness (IMT) of the carotid artery and associated clinical factors in Japanese stroke patients with hyperlipidemia from a cohort of the Japan Statin Treatment Against Recurrent Stroke Echo Study. METHODS Patients with hyperlipidemia, not on statins, who developed noncardioembolic ischemic stroke were included in this study. Mean IMT and maximum IMT of the distal wall of the common carotid artery were centrally measured using carotid ultrasonography. Significant factors related to mean IMT and maximum IMT were examined using multivariable analysis. RESULTS In 793 studied patients, mean IMT was 0.89±0.15 mm and maximum IMT was 1.19±0.32 mm.Age (per 10 years, parameter estimate=0.044, p<0.001), smoking (0.022, p=0.004), category of blood pressure (0.022, p=0.006), HDL cholesterol (per 10 mg/dl, -0.009, p=0.008), and diabetes mellitus (0.033, p=0.010) were independently associated with mean IMT. Age (per 10 years, 0.076, p<0.001), smoking (0.053, p=0.001), HDL cholesterol (-0.016, p=0.036), and diabetes mellitus (0.084, p=0.002) were independently associated with maximum IMT. CONCLUSION Baseline mean and maximum values of carotid IMT in Japanese noncardioembolic stroke patients with hyperlipidemia were 0.89±0.15 mm and 1.19±0.32 mm, respectively, which were similar to those previously reported from Western countries. Age, smoking, hypertension, HDL cholesterol, and diabetes mellitus were associated with mean IMT, and those, except for hypertension, were associated with maximum IMT.
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Active vitamin D analogs, maxacalcitol and alfacalcidol, as maintenance therapy for mild secondary hyperparathyroidism in hemodialysis patients - a randomized study.
Honda, H, Koiwa, F, Ogata, H, Shishido, K, Sekiguchi, T, Michihata, T, Ogawa, H, Mukai, M, Takahashi, K, Suzuki, R, et al
International journal of clinical pharmacology and therapeutics. 2014;(5):360-8
Abstract
BACKGROUND The present randomized study was designed to compare the efficacy between two active vitamin D analogs, alfacalcidol (ACD) and maxacalcitol (OCT), for the management of mild secondary hyperparathyroidism (SHPT) in dialysis patients. METHODS SHPT in all 32 patients analyzed in the study was initially treated with OCT. Once patients' intact PTH levels decreased to the target range of 150 - 180 pg/mL, they were randomized either to switch to ACD at 0.5 μg/day (n = 14), or to remain on an effectively unchanged dose of OCT (n = 13). Phosphate, calcium, and intact PTH levels were measured every 2 weeks for 12 weeks and vitamin D doses were changed according to target ranges of phosphate (3.5 - 6.0 mg/dL), calcium (albuminadjusted calcium: 8.4 - 10.0 mg/dL), and intact parathyroid hormone (60 - 180 pg/mL). Achievement rates of the target ranges of the parameters were estimated. RESULTS Baseline calcium levels in the OCT group were significantly higher than in the ACD group. Changes in achievement rates of target ranges of intact PTH and calcium during the study did not differ significantly between the vitamin D drugs. Changes in calcium levels in the OCT and ACD groups were similar during the study. Achievement rates of the target range of phosphate in both groups were also similar until 8 weeks, although the rate in the OCT group declined at 10 weeks. CONCLUSIONS The efficacy and safety of OCT for the treatment of mild SHPT are similar to those of ACD in hemodialysis patients.