scholarly journals 2-Deoxy-D-Glucose as an Adjunct to Standard of Care in the Medical Management of COVID-19: A Proof-of-Concept & Dose-Ranging Randomised Clinical Trial

2021 ◽  
Author(s):  
Anant Narayan Bhatt ◽  
Srinivas Shenoy ◽  
Sagar Munjal ◽  
Vijayakumar Chinnadurai ◽  
Apurva Agarwal ◽  
...  
Keyword(s):  
Vital Signs ◽  
Standard Of Care ◽  
Randomised Clinical Trial ◽  
Phase Iii ◽  
Ordinal Scale ◽  
Current Phase ◽  
Efficacy And Safety ◽  
Clinical Recovery ◽  
Clinical Benefits ◽  
Isolation Ward

ABSTRACT Objective: To evaluate the efficacy and safety of 2-deoxy-D-glucose (2-DG) in the treatment of COVID-19. Participants: 110 adults aged 18 to 65 years with moderate to severe COVID-19. Interventions: 63, 90, and 126 mg/kg/day 2-DG plus standard of care (SOC) versus SOC only. Main Outcome Measures: Times to maintaining SpO2 ≥94% on room air discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO 10-point ordinal scale, negative conversion on RT-PCR, intensive care, and mortality. Results: Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs 5 days, Hazard ratio [95% confidence interval]=2.3 [1.14, 4.64], p=0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalisation were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild. Conclusion: 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefits over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase-II study encourage confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase-III trial.

DREAMM-9: Phase III study of belantamab mafodotin plus VRd versus VRd alone in transplant-ineligible newly diagnosed multiple myeloma (TI NDMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8556-TPS8556 ◽  
Author(s):  
Saad Zafar Usmani ◽  
Evangelos Terpos ◽  
Wojt Janowski ◽  
Hang Quach ◽  
Sarah West ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Open Label

TPS8556 Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is the standard of care for transplant-eligible and TI NDMM, but relapse is usually inevitable. The median progression-free survival (PFS) is ~3 years for patients with TI NDMM, and with each relapse, the duration of response (DoR) diminishes, highlighting the need for novel, effective, targeted agents. Single-agent belantamab mafodotin is a first-in-class B-cell maturation antigen–binding, humanized, afucosylated, monoclonal immunoconjugate, showing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma ( Lancet Oncol2020). Preclinical work suggests belantamab mafodotin plus bortezomib or lenalidomide enhances anti-myeloma activity. Therefore, studying clinical activity of belantamab mafodotin in combination with these agents is warranted. Methods: DREAMM-9 (NCT04091126) is a two-part, open-label study to determine efficacy and safety of single-agent belantamab mafodotin with VRd vs. VRd alone in patients with TI NDMM. Patients aged ≥18 years with ECOG status 0–2 and adequate organ system functions will be eligible. Part 1 (dose selection) will evaluate safety/tolerability of belantamab mafodotin with VRd administered by single (Day 1) or split dosing (Days 1 and 8) in ≤5 cohorts (n = 12/cohort): 1.9 mg/kg, 2.5 mg/kg split and single, and 3.4 mg/kg split and single. Six more patients may be added to cohort(s) most likely to be selected as recommended Phase III dose (RP3D). Dose-limiting toxicities and adverse events (AEs) will be assessed, and belantamab mafodotin RP3D determined through modified toxicity probability interval criteria. Part 2 (randomized Phase III) will determine efficacy and safety of belantamab mafodotin at RP3D with VRd vs. VRd alone (n = 750) in two arms randomized 1:1. Dual primary endpoints will be rate of minimal residual disease (MRD) negativity and PFS. Secondary endpoints will be response rates (overall response, complete response, very good partial response or better, sustained MRD negativity), DoR, time to progression, and overall survival. Safety assessment will include AEs, serious AEs and ocular findings. In both parts, belantamab mafodotin will be given with VRd for eight induction cycles and then with Rd for maintenance until disease progression or unacceptable toxicity. Funding: GlaxoSmithKline (209664). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04091126 .

scholarly journals Treatment Landscape of Nonmetastatic Castration-Resistant Prostate Cancer: A Window of Opportunity

2021 ◽  
Vol 11 (11) ◽  
pp. 1190
Author(s):  
Fernando López-Campos ◽  
Antonio Conde-Moreno ◽  
Marta Barrado Los Arcos ◽  
Antonio Gómez-Caamaño ◽  
Raquel García-Gómez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Guidelines ◽  
Standard Of Care ◽  
Phase Iii ◽  
Metastatic Progression ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Medical Need ◽  
Clinical Benefits

The treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) is a highly unmet medical need. The classic treatment approach for these patients—androgen deprivation therapy (ADT) alone—until metastatic progression is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival (OS)—for treatments that combine ADT with apalutamide, enzalutamide, and darolutamide. As a result, these approaches are now included in treatment guidelines and are considered a standard of care. In the present article, we discuss the changing landscape of the management of patients with nmCRPC.

scholarly journals Evaluation of convalescent plasma versus standard of care for the treatment of COVID-19 in hospitalized patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elena Diago-Sempere ◽  
José Luis Bueno ◽  
Aránzazu Sancho-López ◽  
Elena Múñez Rubio ◽  
Ferrán Torres ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Respiratory Infections ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Viral Disease ◽  
Multicenter Trial ◽  
Adult Patients ◽  
Ordinal Scale ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/design The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to category 5, 6, or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment. Discussion This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration ClinicalTrials.gov NCT04345523. Registered on 30 March, 2020. First posted date: April 14, 2020.

scholarly journals Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials

2021 ◽  
Vol 13 ◽  
pp. 175883592110011
Author(s):  
Ramez N. Eskander ◽  
Matthew A. Powell
Keyword(s):  
Clinical Trials ◽  
Endometrial Cancer ◽  
Standard Of Care ◽  
Phase Iii ◽  
Oncologic Outcomes ◽  
Current Phase ◽  
Advanced Stage ◽  
Cancer Review ◽  
Oncology Clinical Trials ◽  
Recurrent Endometrial Cancer

The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.

scholarly journals The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study

2021 ◽  
Author(s):  
Nikita V. Lomakin ◽  
Bulat A. Bakirov ◽  
Denis N. Protsenko ◽  
Vadim I. Mazurov ◽  
Gaziyavdibir H. Musaev ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Rescue Therapy ◽  
Subcutaneous Administration ◽  
Phase Iii ◽  
Ordinal Scale ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Improvement Rate ◽  
Double Blind Placebo

Abstract Objective and design The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. Trail registration The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

scholarly journals A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation

2019 ◽  
Vol 5 (4) ◽  
pp. 00167-2019 ◽  
Author(s):  
Aldo Iacono ◽  
Marniker Wijesinha ◽  
Keshava Rajagopal ◽  
Natalia Murdock ◽  
Irina Timofte ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Bronchiolitis Obliterans ◽  
Lung Transplant ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Randomised Clinical Trial ◽  
Bronchiolitis Obliterans Syndrome ◽  
Forced Expiratory Volume ◽  
Phase Iii ◽  
Free Survival

IntroductionNo proven treatments exist for bronchiolitis obliterans syndrome (BOS) following lung transplantation. Inhaled liposomal cyclosporine (L-CsA) may prevent BOS progression.MethodsA 48-week phase IIb randomised clinical trial was conducted in 21 lung transplant patients with BOS assigned to either L-CsA with standard-of-care (SOC) oral immunosuppression (L-CsA group) or SOC (SOC-alone group). Efficacy end-points were BOS progression-free survival (defined as absence of ≥20% decline in forced expiratory volume in 1 s (FEV1) from randomisation, re-transplantation or death) and BOS grade change.ResultsBOS progression-free survival was 82% for L-CsA versus 50% for SOC-alone (p=0.1) and BOS grade worsened in 18% for L-CsA versus 60% for SOC-alone (p=0.05). Mean changes in ΔFEV1 and forced vital capacity, respectively, stabilised with L-CsA: +0.005 (95% CI −0.004– +0.013) and −0.005 (95% CI −0.015– +0.006) L·month−1, but worsened with SOC-alone: −0.023 (95% CI −0.033– −0.013) and −0.026 (95% CI −0.039– −0.014) L·month−1 (p<0.0001 and p=0.009). Median survival (4.1 versus 2.9 years; p=0.03) and infection rate (45% versus 60%; p=0.7) improved with L-CsA versus SOC-alone; creatinine and tacrolimus levels were similar.ConclusionsL-CsA was well tolerated and stabilised lung function in lung transplant recipients affected by BOS without systemic toxicity, providing a basis for a global phase III trial using L-CsA.

scholarly journals Efficacy and Safety of Polyherbal formulation as an add-on to the standard of care in mild to moderate COVID-19: A randomized, double-blind, placebo-controlled trial

2021 ◽  
Author(s):  
Suresh Balkrishna Patankar ◽  
Hrishikesh Rangnekar ◽  
Kalpana Joshi ◽  
Kishor Suryawanshi ◽  
Pravin Soni ◽  
...  
Keyword(s):  
Viral Load ◽  
Rating Scale ◽  
Virus Disease ◽  
Numerical Rating Scale ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Immunomodulatory Activity ◽  
Efficacy And Safety ◽  
Polyherbal Formulation

ABSTRACT Objective: To assess the efficacy and safety of polyherbal formulation (designated as IP) in comparison to placebo as add on to the standard of care (SoC) among patients with mild to moderate novel corona virus disease 2019 (COVID-19) Methods: Laboratory proved patients of mild to moderate COVID-19 disease were randomized to either placebo or IP as an add-on to SoC. Using quantitative reverse transcription-polymerase chain reaction (qRTPCR), we assessed the effect on viral load (VL). Change in immunological parameters such as blood lymphocyte subset, serum immunoglobulin was determined. The clinical improvement was assessed using a numerical rating scale (NRS) and WHO ordinal scale. Patients were followed for 30 days after randomization. Results:In total, 72 patients were randomized to either placebo (n=33) and IP (n=39). Fifty-two patients (n=21 in placebo and n=31 in IP arm) had qRT-PCR on day 0 and day 4. There was significant reduction in VL in IP arm (from 662081 copies/mL on day 0 to 48963 copies/mL on day 4; p=0.002)) but not in the placebo arm (from 385670 copies/mL on day 0 to 66845 copies/mL on day 4, p=0.106). Change in the NRS score and WHO ordinal scale score was significant in both treatment arms. However, the difference between the two groups was statistically significant in favour of drug group, . The increase in Th1 response was significant in the IP arm (p=0.023) but not in the placebo arm (p=0.098), thus implying immunomodulatory activity in the drug. No safety concerns were observed in any of the trial participants. Conclusion: This study finds that polyherbal formulation reduces viral load and contributes to immunomodulation and improvement in clinical conditions when used as add-on to the standard care in patients with mild to moderate COVID-19 without any side effects. These findings need to be further confirmed in a large, prospective, randomized study. Keywords: COVID-19, herbal medication, viral load, immuno modulation.

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