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Trial record 1 of 1 for:    activ-3 | Covid19
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ACTIV-3: Therapeutics for Inpatients With COVID-19 (TICO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04501978
Recruitment Status : Active, not recruiting
First Posted : August 6, 2020
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
University of Copenhagen
Medical Research Council
Kirby Institute
Washington D.C. Veterans Affairs Medical Center
AIDS Clinical Trials Group
National Heart, Lung, and Blood Institute (NHLBI)
US Department of Veterans Affairs
Prevention and Early Treatment of Acute Lung Injury (PETAL)
Cardiothoracic Surgical Trials Network (CTSN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.

Condition or disease Intervention/treatment Phase
Covid19 Drug: LY3819253 Drug: Placebo Drug: Remdesivir Phase 3

Detailed Description:

This is a master protocol to evaluate the safety and efficacy of multiple investigational agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly enhancing viral control in order to limit disease progression.

The protocol is for a randomized, blinded, controlled platform study that allows investigational drugs to be added and dropped during the course of the study. This allows for efficient testing of new drugs against placebo and standard of care (SOC) treatment within the same study. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.

This platform study involves 2 stages. In stage 1, safety will be evaluated and two intermediate outcomes will be assessed to determine whether a drug advances to stage 2. Treatments considered to have demonstrated unacceptable risks relative to benefits, or those which do not reach the effectiveness threshold for the stage 1 intermediate outcomes, will not advance to stage 2. In some cases, stage 1 may include 2 or 3 doses of the same investigational drug, which will be considered separate drugs for the purpose of the study.

Investigational drugs with reasonably well-established safety profiles and evidence of effectiveness (i.e. at least equivalent to the criteria for advancement of a drug from stage 1 to stage 2) may enter the study directly at stage 2. Conversely, for drugs with minimal pre-existing safety evidence, the pace of stage 1 will initially be restricted and there will be an early review of safety data by an independent Data and Safety Monitoring Board (DSMB). A Phase 1 dose escalation study for some investigational drugs may be required, and if so, the Phase 1 study would precede stage 1 and be carried out as a separate protocol.

The international trials within this protocol will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19
Actual Study Start Date : August 4, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ACTIV-3 Drug plus SOC
Participants in this study will be randomized to receive ACTIV-3 Drug plus Standard of Care (SOC) or placebo plus SOC
Drug: LY3819253
Administered by IV infusion

Drug: Remdesivir
Provided to all study participants as SOC unless contraindicated for an individual patient.

Placebo Comparator: Placebo plus SOC
The placebo arm may be pooled across more than one experimental arm if multiple investigational drugs are available to be tested at the same time. If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study
Drug: Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion

Drug: Remdesivir
Provided to all study participants as SOC unless contraindicated for an individual patient.




Primary Outcome Measures :
  1. Pulmonary ordinal outcome (Stage 1) [ Time Frame: Day 5 ]
    Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

  2. Pulmonary+ ordinal outcome (Stage 1) [ Time Frame: Day 5 ]
    Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

  3. Time from randomization to sustained recovery (Stage 2) [ Time Frame: Up to Day 90 ]
    Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.


Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: Thru Day 90 ]
  2. Composite of time to sustained recovery and mortality [ Time Frame: Thru Day 90 ]
  3. Days alive outside short-term acute care hospital [ Time Frame: Up to Day 90 ]
  4. Pulmonary ordinal outcome [ Time Frame: Days 1-7, 14 and 28 ]
    Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

  5. Pulmonary+ ordinal outcome [ Time Frame: Days 1-7 ]
    Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

  6. Change in New Early Warning (NEW) Score [ Time Frame: Baseline to Day 5 ]
    Total of: Respiratory rate (breaths per minute) scored from 0 to +3; Oxygen saturation (%) scored from 0 to +3; Any supplemental oxygen scored from 0 to +2; Temperature scored from 0 to +3; Systolic BP scored from 0 to +3; Heart rate (beats per minute) scored from 0 to +3.; and AVPU (alert, voice, pain, unresponsive) scored from 0 to +3. A higher score denotes a worse outcome.

  7. Incidence of clinical organ failure [ Time Frame: Thru Day 28 ]
  8. Composite of death or serious clinical COVID-19 related events [ Time Frame: Thru Day 90 ]
  9. Composite of cardiovascular events and thromboembolic events [ Time Frame: Thru Day 90 ]
  10. Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death [ Time Frame: Thru Days 5 and 28 ]
  11. Incidence of infusion reactions [ Time Frame: Thru Day 0 ]
  12. Composite of SAEs or death [ Time Frame: Thru Day 90 ]
  13. Change in SARS-CoV-2 neutralizing antibody levels [ Time Frame: Baseline to Days 1, 3, 5, 28 and 90 ]
  14. Change in overall titers of antibodies [ Time Frame: Baseline to Days 1, 3, 5, 28 and 90 ]
  15. Change in neutralizing antibody levels [ Time Frame: Baseline to Days 1, 3, 5, 28 and 90 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent.
  • Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19 infection.
  • Symptoms of COVID-19 for ≤ 12 days.
  • Require admission to hospital for acute medical care (not for purely public health or quarantine purposes).

Exclusion Criteria:

  • Patients who have received plasma from a person who recovered from COVID-19 or who have received neutralizing monoclonal antibodies at any time prior to hospitalization.
  • Patients not willing to abstain from participation in other COVID-19 treatment trials until after Day 5 of the study.
  • Any condition which, in the opinion of the responsible investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
  • Patients considered unable to participate in study procedures.
  • Women of child-bearing potential who are not already pregnant at study entry and who are unwilling to abstain from sexual intercourse with men, or practice appropriate contraception through Day 90 of the study.
  • Men who are unwilling to abstain from sexual intercourse with women of child-bearing potential or who are unwilling to use barrier contraception through Day 90 of the study.
  • [Stage 1 only] Presence at study enrollment of any of the following:

    1. stroke
    2. meningitis
    3. encephalitis
    4. myelitis
    5. myocardial ischemia
    6. myocarditis
    7. pericarditis
    8. symptomatic congestive heart failure
    9. arterial or deep venous thrombosis or pulmonary embolism
  • [Stage 1 only] Current or imminent requirement for any of the following:

    1. invasive mechanical ventilation
    2. ECMO (extracorporeal membrane oxygenation)
    3. Mechanical circulatory support
    4. vasopressor therapy
    5. commencement of renal replacement therapy at this admission (i.e. not patients on chronic renal replacement therapy).

Other investigational drug protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04501978


Locations
Show Show 61 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
University of Copenhagen
Medical Research Council
Kirby Institute
Washington D.C. Veterans Affairs Medical Center
AIDS Clinical Trials Group
National Heart, Lung, and Blood Institute (NHLBI)
US Department of Veterans Affairs
Prevention and Early Treatment of Acute Lung Injury (PETAL)
Cardiothoracic Surgical Trials Network (CTSN)
Investigators
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Principal Investigator: Prof. Jens Lundgren INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
Study Chair: Prof. James Neaton INSIGHT Statistical and Coordinating Centre, University of Minnesota
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04501978    
Other Study ID Numbers: 014 / ACTIV-3
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
COVID-19
COVID 19
SARS-CoV-2
ACTIV-3
ACTIV3
Coronaviridae Infections
Coronavirus Infections
RNA Virus Infections
Virus Diseases
Nidovirales Infections
SARS Coronavirus