Purpose

This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 75 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent data and safety monitoring board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. Subjects will be assessed daily while hospitalized. Discharged subjects will be asked to attend study visits at Days 15 and 29. All subjects will undergo a series of efficacy, safety, and laboratory assessments. The primary objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19.

Condition

Eligibility

Eligible Ages
Between 18 Years and 99 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.
  2. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
  3. Understands and agrees to comply with planned study procedures.
  4. Agrees to the collection of oropharyngeal (OP) swabs.
  5. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
  6. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen collected < 72 hours prior to randomization.

Note - 72 hours is not necessarily time from initial diagnosis. If > / = 72 hours since positive PCR, the PCR may be repeated to assess eligibility.

7. Illness of any duration, and at least one of the following:

- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

- Clinical assessment (evidence of rales/crackles on exam) AND SpO2 < / = 94% on room air, OR

- Requiring supplemental oxygen, OR

- Requiring mechanical ventilation.

8. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.

9. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29.

Exclusion Criteria

  1. Alanine Transaminase (ALT)/Aspartate Transaminase (AST) > 5 times the upper limit of normal.
  2. Estimated glomerular filtration rate (eGFR) < 50 or requiring dialysis.
  3. Pregnancy or breast feeding.
  4. Anticipated transfer to another hospital which is not a study site within 72 hours.
  5. Allergy to any study medication.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Placebo
200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo for the duration of the hospitalization up to a 10 days total course. n=220.
  • Other: Placebo
    The supplied matching placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients.
Experimental
Remdesivir
200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir for the duration of the hospitalization up to a 10 days total course. n=220.
  • Drug: Remdesivir
    Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.

Recruiting Locations

University of Texas Medical Branch - Division of Infectious Disease
Galveston, Texas 77555-0435

More Details

Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

20-0006 Central Contact
13017617948
DMIDClinicalTrials@niaid.nih.gov

Detailed Description

This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 75 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent data and safety monitoring board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. The initial sample size is calculated to be approximately 440 subjects, and if any additional therapeutic arms are added, the sample size will be recalculated. Subjects will be assessed daily while hospitalized. Discharged subjects will be asked to attend study visits at Days 15 and 29. All subjects will undergo a series of efficacy, safety, and laboratory assessments. The primary objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19. The secondary objectives of the study are to 1) evaluate the clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by clinical severity, hospitalization, and mortality, and 2) evaluate the safety of different investigational therapeutics as compared to the control arm.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.