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ACTIV-2: A Study for Outpatients With COVID-19

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04518410
Recruitment Status : Recruiting
First Posted : August 19, 2020
Last Update Posted : November 24, 2020
Sponsor:
Collaborators:
Eli Lilly and Company
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE August 17, 2020
First Posted Date  ICMJE August 19, 2020
Last Update Posted Date November 24, 2020
Actual Study Start Date  ICMJE August 19, 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Duration of COVID-19 symptoms (Phase 2) [ Time Frame: Up to Day 28 ]
    Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)
  • Post-treatment presence of SARS-CoV-2 RNA at Day 3 (Phase 2) [ Time Frame: Day 3 ]
    Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs
  • Post-treatment presence of SARS-CoV-2 RNA at Day 7 (Phase 2) [ Time Frame: Day 7 ]
    Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs
  • Post-treatment presence of SARS-CoV-2 RNA at Day 14 (Phase 2) [ Time Frame: Day 14 ]
    Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs
  • Post-treatment presence of SARS-CoV-2 RNA at Day 21 (Phase 2) [ Time Frame: Day 21 ]
    Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs
  • Post-treatment presence of SARS-CoV-2 RNA at Day 28 (Phase 2) [ Time Frame: Day 28 ]
    Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs
  • Incidence of new adverse event (AE) ≥ Grade 3 (Phase 2) [ Time Frame: Thru Day 28 ]
  • Cumulative incidence of death from any cause or hospitalization (Phase 3) [ Time Frame: Thru Day 28 ]
    ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19
  • Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 3) [ Time Frame: Thru Day 28 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Cumulative incidence of death from any cause or hospitalization (Phase 2) [ Time Frame: Thru Day 28 ]
    ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19
  • Duration of COVID-19 symptoms (Phase 3) [ Time Frame: Up to Day 28 ]
    Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)
  • Presence of SARS-CoV-2 RNA (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Measured as detectable or undetectable, from participant-collected nasal swabs
  • Level of SARS-Cov-2 RNA (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Measured from participant-collected nasal swabs
  • COVID-19 severity ranking (Phases 2 and 3) [ Time Frame: From Day 0 thru Day 28 ]
    Based on symptom severity scores. Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3). For participants who are alive at 28 days and not previously hospitalized, the severity ranking will be based on the area under the curve (AUC) of the symptom score associated with COVID-19 disease over time. Participants hospitalized or who die during follow-up through 28 days will be ranked as worse than those alive and never hospitalized as follows (in worsening rank order): alive and not hospitalized at 28 days; hospitalized but alive at 28 days; and died at or before 28 days.
  • Incidence of ≥1 worsening symptom of COVID-19 (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Progression of one or more COVID-19-associated symptoms to a worse status than recorded at study entry, prior to start of investigational product or placebo
  • Duration of fever (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Defined as the last day in the participant's study diary on which a temperature ≥ 38°C (100.4°F) was recorded or a potentially antipyretic drug was taken.
  • Time to self-report return to usual (pre-COVID-19) health (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    As recorded in participant's study diary
  • Cumulative incidence of death from any cause or hospitalization (Phases 2 and 3) [ Time Frame: Day 0 thru Week 24 ]
  • Oxygen saturation level (Phase 2) [ Time Frame: Thru Day 28 ]
    Measured by pulse oximeter and categorized as <96% versus ≥96%
  • Level of SARS-CoV-2 RNA from site-collected NP swabs (Phase 2) [ Time Frame: Days 0, 3, 7, 14, 21 and 28 ]
    Measured by AUC and above assay lower limit of quantification
  • Level of SARS-CoV-2 RNA from saliva (Phase 2) [ Time Frame: Days 0, 3, 7, 14, 21 and 28 ]
    Measured by AUC and above assay lower limit of quantification
  • Level of SARS-CoV-2 RNA from self-collected nasal swabs (Phase 2) [ Time Frame: Daily at Days 0-14, plus Days 21 and 28 ]
    Measured by AUC and above assay lower limit of quantification
  • Level of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Days 3, 7, 14, 21 and 28 ]
    From site-collected NP swabs
  • Post-treatment presence of SARS-CoV-2 RNA in saliva (Phase 2) [ Time Frame: Days 3, 7, 14, 21 and 28 ]
    Measured as detectable or undetectable
  • Post-treatment level of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Days 3, 7, 14, 21 and 28 ]
    Measured from saliva samples
  • Incidence of new adverse event (AE) ≥ Grade 3 (Phase 3) [ Time Frame: Thru Week 24 ]
  • Concentration of investigational agent (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Analyses of plasma samples collected from placebo-treated participants are not planned
  • Level of anti-drug antibodies (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Analyses of plasma samples collected from placebo-treated participants are not planned
  • AUC (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Area under the concentration-time curve. Analyses of plasma samples collected from placebo-treated participants are not planned
  • Total body clearance (CL) (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Analyses of plasma samples collected from placebo-treated participants are not planned
  • Elimination half-life (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    T1/2. Analyses of plasma samples collected from placebo-treated participants are not planned
  • Cmax (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Maximum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned
  • Cmin (Phase 2 - LY3819253) [ Time Frame: Days 0, 14, 28, Week 12, Week 24 ]
    Minimum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ACTIV-2: A Study for Outpatients With COVID-19
Official Title  ICMJE Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)
Brief Summary

Drug studies often look at the effect one or two drugs have on a medical condition, and involve one company. There is currently an urgent need for one study to efficiently test multiple drugs from more than one company, in people who have tested positive for COVID-19 but who do not currently need hospitalization. This could help prevent disease progression to more serious symptoms and complications, and spread of COVID-19 in the community.

This study looks at the safety and effectiveness of different drugs in treating COVID-19 in outpatients. Participants in the study will be treated with either a study drug or with placebo.

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 study is designed to transition from phase 2 to phase 3 in the same trial, with or without a pause in enrollment, depending on the speed of enrollment and interim results. For promising agents with limited availability, a phase 3 evaluation may occur at a later time. Up to two dose levels of the same agent may be assessed. Agents may also enter directly into phase 3 evaluation if sufficient safety and efficacy data are available from outside the trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Unblinded data will be provided to the Data and Safety Monitoring Board for interim analyses. Unblinded Day 28 data will also be provided to a small group of people from the company who owns the investigational agent, to assist the company in deciding if the agent should move into phase 3 evaluation; or in choosing a dose of their agent to move into phase 3 evaluation.
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus
  • Covid19
Intervention  ICMJE
  • Drug: LY3819253
    Administered by IV infusion
  • Drug: Placebo
    Commercially available 0.9% sodium chloride solution. Administered by IV infusion
Study Arms  ICMJE
  • Experimental: ACTIV-2 Drug
    Participants in this study will be randomized to receive ACTIV2 Drug or placebo
    Intervention: Drug: LY3819253
  • Placebo Comparator: Placebo
    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
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2020)
2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent.
  • Positive test for COVID-19 up to 7 days before participation in study.
  • Able to begin study treatment no later than 10 days from self-reported onset of COVID-19 related symptom(s):

    • fever or feeling feverish
    • cough
    • shortness of breath or difficulty breathing at rest or when active
    • sore throat
    • body pain or muscle pain/aches
    • fatigue
    • headache
    • chills
    • blocked nose/nasal congestion
    • runny nose
    • loss of taste or smell
    • nausea or vomiting
    • diarrhea
    • temperature ≥ 38°C (100.4°F)
  • One or more of the following signs/symptoms within 48 hours of participating in the study:

    • fever or feeling feverish
    • cough
    • shortness of breath or difficulty breathing at rest or when active
    • sore throat
    • body pain or muscle pain/aches
    • fatigue
    • headache
    • chills
    • blocked nose/nasal congestion
    • runny nose
    • loss of taste or smell
    • nausea or vomiting
    • diarrhea
    • temperature ≥ 38°C (100.4°F)
  • Oxygen levels of ≥92% when resting (measured by study staff within 48 hours of participating in the study), unless participant is receiving long-term supplementary oxygen for an underlying lung condition.
  • Participant must agree not to participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period until hospitalization or 28 days after the start of the study, whichever occurs first.

Exclusion Criteria:

  • History of or current hospitalization for COVID-19.
  • Current need for hospitalization or immediate medical attention.
  • Any use of the following medications up to 30 days before participating in the study:

    • Hydroxychloroquine (except for long-term autoimmune diseases)
    • Chloroquine and/or ivermectin (unless used for parasitic infection)
    • Remdesivir, systemic and inhaled steroids (unless used for long-term conditions)
    • HIV protease inhibitors (unless used long-term for HIV infection)
  • Receipt of plasma from a person who recovered from COVID-19 any time before participating in the study.
  • Receipt of a SARS-CoV-2 vaccine any time before participating in the study.
  • Receipt of other investigational treatments for SARS-CoV-2 any time before participating in the study (not including drugs approved and taken for other conditions/diseases).
  • Receipt of systemic steroids (e.g. prednisone, dexamethasone) or inhaled steroids up to 30 days before participating in the study, unless this is a stable dose for a long-term condition.
  • Known allergy/sensitivity or hypersensitivity to study drug or placebo.
  • Any condition requiring surgery up to 7 days before participating in the study, or that is considered life threatening up to 30 days before participating in the study.

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04518410
Other Study ID Numbers  ICMJE A5401/ACTIV-2
38742 ( Other Identifier: DAIDS-ES )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Eli Lilly and Company
  • AIDS Clinical Trials Group
Investigators  ICMJE
Study Chair: David Smith, MD, MAS University of California, San Diego
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP