April 27, 2020
NOT-OD-20-077
PA-20-135 Emergency Competitive Revision to Existing NIH Awards (Emergency Supplement - Clinical Trial Optional)
NOT-HL-20-789 -
Notice of Expiration of NOT-HL-20-757
NOT-HL-20-800 - Notice of Expiration of NOT-HL-20-782
National Heart, Lung, and Blood Institute (NHLBI)
NHLBI is issuing this Notice of Special Interest (NOSI) due to the urgent need for early phase clinical trials to evaluate new or existing interventions that may prevent or treat Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NHLBI seeks to leverage existing clinical trials expertise and, using NHLBI programs that are actively conducting Phase I-III clinical trials, to rapidly initiate and conduct Phase I-Phase I/II (bridging) clinical trials in patients at risk for SARS-CoV-2 infection and/or patients with COVID-19. It is strongly recommended that the parent activity code be one of the following: P01, R01, R33, R41, R42, R43, R44, U01, U24, U54, UH3, or UM1.
Topics of specific interest to the NHLBI include the safety and efficacy of interventions for primary prevention and/or treatment of COVID-19, associated clinical phenotypes, and surrogate outcomes, relevant to heart, lung, and blood (HLB) diseases.
Programs currently conducting research without an active Phase I-III clinical trial may wish to consider applications to NOT-HL-20-757.
Background
Coronaviruses are a diverse family of viruses that cause a range of disease in humans and animals, and there are currently no approved coronavirus vaccines or therapeutics. In January 2020, a novel coronavirus, SARS-CoV-2, was identified as the causative agent of an outbreak of viral pneumonia centered around Wuhan, China. Current information regarding confirmed cases is changing daily and can be found on the Centers for Disease Control and Prevention website (https://www.cdc.gov/coronavirus/index.html).
Patients diagnosed with this illness have reported symptoms such as fever, cough, shortness of breath, fatigue, myalgias, headache, sore throat, abdominal pain, and diarrhea. Patients admitted to the hospital generally have pneumonia and abnormal chest imaging, and complications include acute respiratory failure, acute respiratory distress syndrome (ARDS), and acute myocardial injury. The severity of illness and course of the infection is heterogenous and appears to be more severe in the elderly and in individuals with underlying comorbidities, including cardiovascular and chronic respiratory diseases. Emerging evidence indicates that cytokine storm is associated with severity and early cardiac injury. Additionally, ARDS, thrombocytopenia and disseminated intravascular coagulopathy (DIC) are associated with severity and mortality.
Specific Area of Research Interest
This NOSI is applicable to active NHLBI, Phase I-III single or multisite clinical trials that seek to conduct Phase I-Phase I/II (bridging) for COVID-19. For the purposes of this NOSI, the definition of a bridging study is a study performed to provide clinical data that allows extrapolation of existing data from a population for whom an intervention product has been approved, in order to bring the intervention product to a new population (e.g., into a new disease indication, adults into peds, etc.). In addition to the primary aim of assessing the safety of the intervention product, secondary aims may include: 1) further testing of the intervention's feasibility and acceptability; 2) determining the optimal dose for a subsequent trial by assessing dose-response with respect to a functional pharmacodynamic readout biological signature in response to product; 3) determining the pharmacokinetics of the dose and formulation of the product to be used in future trials to justify the frequency of dosing; and 4) developing functional biological signature measures and clinical outcome measures feasible for use in larger efficacy and effectiveness studies in heterogeneous populations or subpopulations. The specific activities proposed will depend on the product under study and available preliminary data on the product. Supported research is expected to inform future efforts to diagnose, prevent, mitigate, or treat this viral infection and associated manifestations.
Research examples that would be responsive to this NOSI includes but are not limited to:
Research proposals from programs conducting clinical research outside of an active Phase I-III clinical trial that do not have the appropriate investigator team expertise in safety, efficacy and/or management trials are not responsive to this NOSI and will be withdrawn without review.
Required Capabilities
Applicants responding to this NOSI must have appropriate capabilities, infrastructure, and attributes. These key components are expected to ensure qualified personnel and site capabilities for the safe conduct of Phase I-Phase I/II (bridging) for COVID-19.
Initiation of Enrollment
Investigators applying for this NOSI must be prepared to initiate enrollment within the first quarter of the award.
Experience in the Conduct of Clinical Trials
It is essential that investigators applying for these awards have expertise and well-documented past performance in the conduct of Phase I-III clinical trials.
Coordination of Clinical Trials and Associated Activities
The awardees will be responsible for all administrative duties, filing adverse event reports, maintenance of all regulatory documents, communications, protocol, consent and forms development, quality control, milestone tracking, and analysis and reporting of outcomes.
Personnel
While necessary personnel may be added to implement the study, the original team must have relevant expertise already in place, along with an appropriate infrastructure to enable the leveraging of existing HLB trials.
Application and Submission Information
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additions:
Section IV. PHS Human Subjects and Clinical Trials Information
Section 2 Study Population Characteristics
Section 2.7 Study Timeline
A table or graph of the overall study timeline must be included and may not exceed 4 pages. This is expected to be a visual representation (such as a Gantt Chart) of estimated trial duration and key milestones. Milestones must be relevant, measurable, results-focused and time-bound (e.g., IND/IDE approval, drug/device supply, recruitment milestones, etc.). A narrative is not expected in this section. The period of time for the study duration is expected to be displayed in months and must include, but is not limited to, the following:
Section 3 - Protection and Monitoring Plan
3.3 Data and Safety Monitoring Plan
Describe the process that will be utilized to identify anticipated and unanticipated problems and describe procedures for adverse event reporting, intervention discontinuation, and stopping guidelines, with an appropriate ongoing monitoring process. Parent trial Data and Safety Monitoring Boards (DSMBs) may be proposed to monitor the proposed trial, however, NHLBI reserves the right to require additional expertise be added, or an independent monitoring process.
Section 5 - Other Clinical-Trial Related Attachments
5.1 Other Clinical Trial-related Attachments
Applicants must provide a detailed table listing the characteristics of trials that demonstrate experience in trial coordination in the last 5 years. The table must be provided as an attachment called "Early Phase Clinical Trial Experience.pdf" and may not exceed 3 pages.
The table columns should include:
Column A: clinical study title (include ClinicalTrials.gov number)
Column B: applicant's role in the study
Column C: a brief description of the study design
Column D: planned enrollment
Column E: actual enrollment
Column F: number of sites
Column G: whether the studies were completed on schedule or not
Column H: publication reference(s)
Please direct all inquiries to:
Patricia Noel, PhD
National Heart, Lung, and Blood Institute
Division of Lung Diseases
Telephone: 301-435-0202
Email: [email protected]
Nahed El Kassar, MD, PhD
National Heart, Lung, and Blood Institute
Division of Blood Diseases and Resources
Telephone: 301-827-8268
Email: [email protected]
Emily Tinsley PhD, MS
National Heart, Lung, and Blood Institute
Division of Cardiovascular Sciences
Telephone: 301-435-0519
Email: [email protected]