Accelerated First-in-Human Clinical Trial of EIDD-2801/MK-4482 (molnupiravir), a Ribonucleoside Analogue with Potent Antiviral Activity Against SARS-CoV-2

2021 ◽  
Author(s):  
Oren Cohen ◽  
Wendy Holman ◽  
Wayne Holman ◽  
Wendy Painter ◽  
Stacy McIntosh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antiviral Agent ◽  
Pharmacokinetic Profile ◽  
Phase 2 ◽  
Contract Research Organization ◽  
Regulatory Authorities ◽  
The United Kingdom ◽  
Global Pandemic ◽  
The Us ◽  
Working Groups

Abstract A recently published article described the safety, tolerability and pharmacokinetic profile of molnupiravir, a novel antiviral agent with potent activity against SARS-CoV-2, the causative agent of COVID-19. Here, we report an unprecedented collaboration between sponsor, contract research organization (CRO) and regulatory authorities that enabled accelerated generation of these phase I data, including administration of the first-in-human (FIH) dose of molnupiravir within 5 days of receiving approval from the Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK). Frequent, direct communication with regulatory authorities and parallel, streamlined sponsor-CRO working groups facilitated this accelerated timeline. Dosing in healthy volunteers was completed for eight single ascending dose (SAD) cohorts, seven multiple ascending dose (MAD) cohorts, and one food-effect (FE) cohort within approximately 16 weeks of initial protocol submission to the REC and MHRA. Working to standard industry timelines, the FIH study would have normally taken approximately 46 weeks to complete and 33 weeks to enable Phase 2 dosing. Data from this study supported submission of a Phase 2/3 clinical trial protocol to the US Food and Drug Administration (FDA) within eight weeks of initial protocol submission, with FDA comments permitting phase 2 study initiation within two additional weeks. In the setting of a global pandemic, this model of collaboration allows for accelerated generation of clinical data compared to standard processes, without compromising safety.

scholarly journals Accelerated first-in-human clinical trial of EIDD-2801/MK-4482 (molnupiravir), a ribonucleoside analog with potent antiviral activity against SARS-CoV-2

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wendy Holman ◽  
Wayne Holman ◽  
Stacy McIntosh ◽  
Wendy Painter ◽  
George Painter ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Food Effect ◽  
Antiviral Agent ◽  
Pharmacokinetic Profile ◽  
Total Daily Dose ◽  
Phase 2 ◽  
Double Blind ◽  
Contract Research Organization ◽  
Fed State ◽  
Global Pandemic

AbstractA recently published article described the safety, tolerability, and pharmacokinetic profile of molnupiravir (Painter et al. 2021), a novel antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Here, we report an unprecedented collaboration between sponsor, contract research organization (CRO), and regulatory authorities that enabled accelerated generation of these phase I data, including administration of the first-in-human (FIH) dose of molnupiravir within 5 days of receiving regulatory approval in the United Kingdom (UK). Single and multiple ascending dose (SAD and MAD, respectively) cohorts were dosed in randomized, double-blind, and placebo-controlled fashion, with a 6:2 active-to-placebo ratio in each cohort. A food-effect (FE) cohort included 10 subjects who were randomized to receive drug in the fasted or fed state followed by the fed or fasted state to complete a fed and fasted sequence for each subject. Dose escalation decisions were accelerated and MAD cohorts were initiated prior to completion of all SAD cohorts with the provision that the total daily dose in a MAD cohort would not exceed a dose proven to be safe and well-tolerated in a SAD cohort. Dosing in healthy volunteers was completed for eight single ascending dose (SAD) cohorts, seven multiple ascending dose (MAD) cohorts, and one food-effect (FE) cohort within approximately 16 weeks of initial protocol submission to the Research Ethics Committee (REC) and Medicines and Healthcare products Regulatory Agency (MHRA). Working to standard industry timelines, the FIH study would have taken approximately 46 weeks to complete and 33 weeks to enable phase 2 dosing. Data from this study supported submission of a phase 2/3 clinical trial protocol to the US Food and Drug Administration (FDA) within 8 weeks of initial protocol submission, with FDA comments permitting phase 2 study initiation within two additional weeks. In the setting of a global pandemic, this model of collaboration allows for accelerated generation of clinical data compared to standard processes, without compromising safety.

scholarly journals Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4861-4861
Author(s):  
Sikander Ailawadhi ◽  
Sri Lekha Bodepudi ◽  
Zan Tahir Shareef ◽  
Fabiola Coromoto Cardozo ◽  
Salman Ahmed ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Geographical Distribution ◽  
Research Funding ◽  
Phase 1 ◽  
The United States ◽  
Phase 2 ◽  
B Cell Malignancies ◽  
The Us

Abstract Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p<0.001) (Figure 3). Conclusions: Widespread access to clinical trials within a cancer diagnosis is imperative for generalizability of trial results. In a comprehensive, national analysis we noted that while it may appear that clinical trials are available across the US, sites where they are open are distributed unevenly, giving rise to a disparity in access to evidence-based therapeutic advancements for patients. Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

Racial distribution of clinical trial participants in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18516-e18516
Author(s):  
Monaliben Patel ◽  
Lisa M. Hess ◽  
Eric Wen Su ◽  
Xiaohong Li ◽  
Debora S. Bruno
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Phase 2 ◽  
Phase 3 ◽  
Black Patients ◽  
The Us ◽  
Oncology Clinical Trials ◽  
Seer Data ◽  
Trial Participants

e18516 Background: Lack of diverse representation in clinical trials negatively impacts the cancer survival of patients and populations unaccounted for in clinical research. Efforts such as the 1993 NIH Revitalization Act have focused on improving the diversity of trial participants in the US. This retrospective study evaluated the racial distribution of oncology clinical trial participants using data published in clinicaltrials.gov from Jan 2010 through Dec 2020. Methods: I2E of Linguamatics (IQVIA, Inc), a natural language processing software, was used to identify participant race in oncology trials. Data extracted included trial identifier, year of completion, sponsor, cancer type, and race. Studies were limited to academic, cooperative group and government studies headquartered in the US. Clinical trial results were compared to the racial distribution of SEER 2010 data using z-test. Results: Data from 35,686 patients (14,220 enrolled to 236 phase 2 and 21,471 enrolled to 47 phase 3 trials) were available for analysis. A summary by race is provided in the Table, excluding unknown, which represented 8.5% of phase 2 and 3.5% of phase 3 trials. The proportions of white/black patients enrolled to phase 2 and phase 3 trials beginning in 2010-12 were 84.4%/11% and 83.1%/9.9%, respectively (total enrollment 84.9%/9.6%). For trials beginning in 2015-17, white/black enrollment represented 88.5%/8.1% of patients enrolled to phase 2 and 86.4%/10.1% of patients in phase 3 trials. Black patients represented 9.6% of all trial participants, in contrast with the SEER data where 12% of all patients were black (p < 0.001). For lung cancer trials, black participants represented only 7.9% of all trial participants whereas in breast cancer trials, 10.2% of participants were black, versus the SEER data specific to these tumor types (black patients represent 10.9%/11.5% of lung/breast cancer diagnoses between 2013 to 2017, both p < 0.01). Conclusions: This study suggests that over the past decade most races (other than white) have been significantly underrepresented in US oncology clinical trials, and is even more pronounced for black patients with lung cancer. Based on this analysis, there is no evidence that trial enrollment distribution, particularly of white versus black participants, has changed since 2010. Data are limited to the relative lack of studies reporting results that began enrollment after 2017. These findings suggest that the development of new strategies to improve the recruitment of racial minorities to oncology clinical trials are warranted.[Table: see text]

scholarly journals Is health politically irrelevant? Experimental evidence during a global pandemic

2020 ◽  
Author(s):  
Arnab Acharya ◽  
John Gerring ◽  
Aaron Reeves
Keyword(s):  
Public Health ◽  
Health Effects ◽  
The United States ◽  
Economic Effects ◽  
Health Issues ◽  
Voter Preferences ◽  
The United Kingdom ◽  
Global Pandemic ◽  
Three Samples ◽  
The Us

This project involves three samples, drawn from the United Kingdom, the United States, and India. Respondents are recruited through MTurk and compensated after the completion of a short survey. In each country, we aim for a sample of 1,500, reserving 500 for each of three treatment arms – a pure control, an “economics” treatment (where we prime the economic effects of the Coronavirus pandemic), and a “public health” treatment (where we prime the health effects of the pandemic). People in the US, UK, and India are extremely concerned about the pandemic – both its health effects and economic repercussions – and they become even more concerned when primed with information about the repercussions of the virus. Yet, we find no evidence that these worries translate into changes in political behavior. The null findings contained in this study suggest that politicians are unlikely to be punished or rewarded for their failures or successes in managing Covid-19 in the next election. We suggest that these findings indicate that public health issues have little influence on voter preferences in most election cycles.

Comparison of a Novel Tazarotene 0.045% Lotion to Tazarotene 0.1% Cream: Patient-Reported Outcomes from a Phase 2 Clinical Trial

2019 ◽  
Vol 3 ◽  
pp. S9
Author(s):  
Zoe Draelos ◽  
Fran Cook-Bolden ◽  
Lawrence Green ◽  
Eric Guenin ◽  
Gina Martin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Patient Reported Outcomes ◽  
Phase 2 ◽  
Patient Reported ◽  
Phase 2 Clinical Trial

Abstract not available.

Too WEIRD, Too Fast: Preprints about COVID-19 in the Psychological Sciences

2020 ◽  
Author(s):  
Arathy Puthillam
Keyword(s):  
Overwhelming Majority ◽  
Global Pandemic ◽  
The Us ◽  
The World ◽  
The Face ◽  
Conducting Research ◽  
Psychological Studies

That American and European participants are overrepresented in psychological studies has been previously established. In addition, researchers also often tend to be similarly homogenous. This continues to be alarming, especially given that this research is being used to inform policies across the world. In the face of a global pandemic where behavioral scientists propose solutions, we ask who is conducting research and on what samples. Forty papers on COVID-19 published in PsyArxiV were analyzed; the nationalities of the authors and the samples they recruited were assessed. Findings suggest that an overwhelming majority of the samples recruited were from the US and the authors were based in US and German institutions. Next, men constituted a large proportion of primary and sole authors. The implications of these findings are discussed.

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