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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 : December 1, 2021
Sponsor:
Collaborators:
Eli Lilly and Company
AIDS Clinical Trials Group
Brii Biosciences Limited
AstraZeneca
Sagent Pharmaceuticals
Synairgen Research Ltd.
Bristol-Myers Squibb
SAb Biotherapeutics, Inc.
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 December 1, 2021
Actual Study Start Date  ICMJE August 19, 2020
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2021)
  • COVID-19 symptom duration (Phase 2) [ Time Frame: Up to Day 28 ]
    Duration defined as the number of days from start of investigational agent to the first of two consecutive days when any symptoms scored as moderate or severe as study entry (pre-treatment) are scored as mild or absent; and any symptoms scored as mild or absent at study entry are scored as absent, AND any symptoms scored as mile or absent at study entry (pre-treatment) are scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); 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)
  • Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 3 ]
    Measured as quantification (<LLoQ versus ≥LLoQ ) from staff-collected NP (nasopharyngeal) swabs
  • Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 7 ]
    Measured as quantification (<LLoQ versus ≥LLoQ ) from staff-collected NP (nasopharyngeal) swabs
  • Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 14 ]
    Measured as quantification (<LLoQ versus ≥LLoQ ) from staff-collected NP (nasopharyngeal) swabs
  • Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 2) [ Time Frame: Thru Day 28 ]
  • Cumulative incidence of death due to any cause or hospitalization due to any cause (Phase 3) [ Time Frame: Thru Day 28 ]
    Hospitalization defined as ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to 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
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2021)
  • COVID-19 symptom duration (Phase 3) [ Time Frame: Thru Day 28 ]
    Duration defined as the number of days from start of investigational agent to the first of two consecutive days when any symptoms scored as moderate or severe as study entry (pre-treatment) are scored as mild or absent; and any symptoms scored as mild or absent at study entry are scored as absent, AND any symptoms scored as mile or absent at study entry (pre-treatment) are scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); 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)
  • Quantification of SARS-CoV-2 RNA (Phase 3) [ Time Frame: Day 3 ]
    Measured as quantification (<LLoQ versus ≥LLoQ ) from staff-collected NP (nasopharyngeal) swabs
  • Cumulative incidence of death from any cause or hospitalization due to any cause (Phase 2) [ Time Frame: Thru Day 28 ]
    Hospitalization defined as ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19
  • Cumulative incidence of death from any cause, or hospitalization due to any cause related to COVID-19 (Phase 3) [ Time Frame: Thru Day 28 ]
    Hospitalizations due to any cause deemed unrelated to COVID-19 are excluded. Hospitalization defined as ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19
  • Level of SARS-CoV-2 RNA from NP swabs (Phase 2) [ Time Frame: Thru Day 14 ]
    Measured from staff-collected NP swabs
  • Level of SARS-CoV-2 RNA from NP swabs (Phase 3) [ Time Frame: Day 3 ]
    Measured from staff-collected NP swabs
  • Duration of targeted clinical COVID-19 symptoms (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Duration defined as the number of days from start of investigational agent to the first of four consecutive days when all symptoms scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); 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)
  • COVID-19 symptom 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.
  • Proportion of participants with ≥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 in study diary at study entry, prior to start of investigational product or placebo
  • Time to self-reported return to usual health (a) (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Defined as the number of days from start of investigational treatment until the first of two consecutive days that a participant reported return to usual (pre-COVID-19) health as recorded in a participant's study diary
  • Cumulative incidence of death due to any cause or hospitalization due to any cause (Phases 2 and 3) [ Time Frame: Day 0 thru Week 24 ]
  • Cumulative incidence of death due to any cause or hospitalization due to any cause (Phases 2 and 3) [ Time Frame: Day 0 thru Week 72 ]
  • Oxygen saturation level (Phase 2) [ Time Frame: Thru Day 28 ]
    Measured by pulse oximeter and categorized as <96% versus ≥96%
  • AUC of SARS-CoV-2 RNA from site-collected NP swabs (Phase 2) [ Time Frame: Thru Day 14 ]
    Measured by area under the curve (AUC) and above assay lower limit of quantification of quantitative SARS-CoV-2 RNA over time
  • Incidence of new adverse event (AE) ≥ Grade 2 (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
  • Incidence of new adverse event (AE) ≥ Grade 2 (Phases 2 and 3) [ Time Frame: Thru Week 24 ]
  • Incidence of new adverse event (AE) ≥ Grade 3 (Phases 2 and 3) [ Time Frame: Thru Week 24 ]
  • Time to self-reported return to usual health (b) (Phases 2 and 3) [ Time Frame: Thru Day 28 ]
    Defined as the number of days from start of investigational treatment until the first of four consecutive days that a participant reported return to usual (pre-COVID-19) health as recorded in a participant's study diary
Original 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
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. In Phase II, participants in the study will be treated with either a study drug or with placebo. In protocol version 7.0, participants in Phase III of the study will be treated with either a study drug or active comparator drug. Participants assigned to the bamlanivimab agent/placebo arm and will have 28 days of intensive follow-up following study drug administration, followed by limited follow-up through 24 weeks in phase II and in phase III. All other investigational agents and their corresponding placebo arms will involve 28 days of intensive follow-up, followed by limited follow-up through 72 weeks in phase II and phase III. Additional study visits may be required, depending on the agent.

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 includes both infused and non-infused agents and is a randomized controlled platform that allows agents to be added and dropped during the course of the study for efficient phase II and phase III testing of new agents within the same trial infrastructure.

Version 7 of the protocol provided for blinded phase II evaluation of an investigational agent for superiority to placebo among participants at lower risk of progression to hospitalization or death, regardless of the mode of administration of the agent.

Agents that graduate to phase III after initiation of the protocol version will be evaluated in persons at higher risk for progression to hospitalization or death for non-inferiority to an active comparator (monocolonal antibody cocktail of casirivimab plus imdevimab (REGEN-COV, Regeneron). This active comparator has been shown to be effective in this population in preventing hospitalization or death. When two or more agents are being evaluated in the same phase of the study, the trial design includes sharing of the control group (placebo in phase II and active comparator in phase III) for efficient evaluation of each agent.

Investigational agents will be approved by the Trial Oversight Committee (TOC) for phase II evaluation based on the presence of in vitro data demonstrating promise as anti-SARS-CoV-2 therapeutics in pre-clinical testing, and for which there are suitable pharmacokinetics and safety data from phase I testing, or through clinical or research testing for a different indication, and agent availability. Investigational agents will be included in phase III evaluation based on agent entry criteria for phase III as outlined in the protocol (or by TOC approval based on data available outside ACTIV-2).

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
  • Biological: bamlanivimab
    7000 mg or 700 mg (Phase 2), 700 mg (Phase 3). Administered by single IV infusion. Phases 2 and 3 completed for bamlanivimab. Participants are no longer being randomized to this intervention.
    Other Name: LY3819253
  • Drug: Placebo (IV)
    Commercially available 0.9% sodium chloride solution.
  • Biological: BRII-196/BRII-198
    1000 mg (BRII-196)/1000 mg (BRII-198) combination therapy. Administered by consecutive IV infusions as single dose. Participants are no longer being randomized to this intervention.
  • Biological: AZD7442 (IV)
    300 mg AZD7442 (150 mg AZD8895 + 150 mg AZD1061). Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.
    Other Name: AZD8895 + AZD1061
  • Biological: AZD7442 (IM)
    Administered intramuscularly as 2 separate injections sequentially (300 mg AZD8895 then 300 mg AZD1061) for one dose. Injections administered in the side of the thigh, one injection in each thigh. Participants are no longer being randomized to this intervention.
    Other Name: AZD8895 + AZD1061
  • Drug: SNG001
    1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device).
  • Drug: Camostat
    200 mg (2 x 100 mg) film-coated tablets administered orally every 6 hours for 7 days. Participants are no longer being randomized to this intervention.
    Other Names:
    • FOY-305
    • camostat mesilate
    • camostat mesylate
  • Drug: Placebo (IM)
    Commercially available 0.9% sodium chloride Injection, USP. Administered intramuscularly as 2 separate injections, sequentially for one dose. Injections administered in the side of the thigh, one injection in each thigh.
  • Drug: Placebo (Inhaled solution)
    Trisodium citrate dihydrate, di-sodium hydrogen-phosphate, sodium dihydrogen-phosphate dihydrate, racemic methionine (DL-methionine) and water. 1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device).
  • Drug: Placebo (oral tablet)
    200 mg (2 x 100 mg) film-coated tablets administered orally every 6 hours for 7 days.
  • Biological: BMS-986414 + BMS-986413
    Administered subcutaneously (SC) as 4 separate injections for one dose (two injections of C135-LS 200mg and two injections of C144-SL 200mg).
    Other Name: C135-LS + C144-LS
  • Drug: Placebo (SC injections)
    Administered SC as 4 separate injections for one dose.
  • Biological: SAB-185 (3,840 Units/kg)
    Administered by IV infusion as single dose.
    Other Name: Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)
  • Biological: SAB-185 (10,240 Units/kg)
    Administered by IV infusion as single dose.
    Other Name: Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)
  • Drug: CASIRIVIMAB + IMDEVIMAB
    600 mg casirivimab and 600 mg imdevimab, administered together as single IV infusion as one-time dose at study entry.
    Other Names:
    • REGN10933 + REGN10987
    • REGN-COV2
Study Arms  ICMJE
  • Experimental: Bamlanivimab
    Administered by IV infusion.
    Intervention: Biological: bamlanivimab
  • Experimental: BRII-196/BRII-198
    Administered by IV infusion.
    Intervention: Biological: BRII-196/BRII-198
  • Experimental: AZD7442 (IV)
    Administered by IV infusion.
    Intervention: Biological: AZD7442 (IV)
  • Experimental: Placebo (IV)
    The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and use the same method of administration. 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 (IV)
  • Experimental: SNG001
    Administered by inhalation.
    Intervention: Drug: SNG001
  • Placebo Comparator: Placebo (Inhaled solution)
    The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way. 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 (Inhaled solution)
  • Experimental: AZD7442 (IM)
    Administered by IM injection.
    Intervention: Biological: AZD7442 (IM)
  • Placebo Comparator: Placebo (IM)
    The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way. 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 (IM)
  • Experimental: Camostat
    Administered as oral tablets.
    Intervention: Drug: Camostat
  • Placebo Comparator: Placebo (oral tablets)
    The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way. 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 (oral tablet)
  • Experimental: BMS 986414 + BMS 986413
    Administered as subcutaneous (SC) injections.
    Intervention: Biological: BMS-986414 + BMS-986413
  • Placebo Comparator: Placebo (SC injections)
    The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way. 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 (SC injections)
  • Experimental: SAB-185 (Lower dose)
    Administered by IV infusion.
    Intervention: Biological: SAB-185 (3,840 Units/kg)
  • Experimental: SAB-185 (Higher dose)
    Administered by IV infusion.
    Intervention: Biological: SAB-185 (10,240 Units/kg)
  • Active Comparator: Casirivimab + Imdevimab (Phase III only)
    Administered by IV infusion
    Intervention: Drug: CASIRIVIMAB + IMDEVIMAB
Publications * Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9:CD013825. doi: 10.1002/14651858.CD013825.pub2. Review.

*   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 17, 2021)
8797
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2020)
2000
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent.
  • Documentation of laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g. oropharyngeal, nasopharyngeal (NP), or nasal swab, or saliva) collected ≤240 hours (10 days) prior to study entry. Laboratory-confirmed SARS-CoV-2 infection outside the US must be conducted at a DAIDS-approved laboratory.
  • Able to begin study treatment no later than 7 days from self-reported onset of COVID-19 related symptom(s) or measured fever, where the first day of symptoms is considered symptom day 0 and defined by the self-reported date of first reported sign/symptom from the following list:

    • subjective 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
    • loss of taste or smell
    • nausea or vomiting
    • diarrhea
    • temperature > 38°C (100.4°F)
  • One or more of the following signs/symptoms within 24 hours of participating in the study:

    • subjective 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
    • loss of taste or smell
    • nausea or vomiting
    • diarrhea
    • temperature > 38°C (100.4°F)
  • Oxygen levels of ≥92% obtained at rest (adjusted as needed for altitude) by study staff within 24 hours of study entry. For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, their oxygen saturation should be measured while on their standard home oxygen supplementation level.
  • 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.
  • Meet the protocol definition of being at "higher" risk of progression to hospitalization or death (BRII-196/BRII-198).
  • In Phase III, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (SNG001, SAB-185, BMS 986414+BMS 986413)
  • For participants of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to study entry by any clinic or laboratory that has a CLIA certification or its equivalent, or by a point of care (POC)/CLIA-waived test. Note: Participants not of reproductive potential are eligible without requiring the use of a contraceptive method (BRII-196/BRII-198. AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
  • Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives for 24 weeks after investigational product is administered. Participants with pregnant partners should use condoms during vaginal intercourse through 24 weeks after investigational agent administration. Participants should refrain from sperm donation for 24 weeks after investigational agent administration (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SAB-185).
  • Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives for 30 days after investigational agent administration. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to sue effective contraceptives for 30 days after investigational agent is administered to the participant. Participants with pregnant partners should use condoms during vaginal intercourse through 30 days after last dose of investigational agent administration. Participants should refrain from sperm donation for 30 days after investigational agent administration (SNG001).
  • Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-regnant sexual partners of reproductive potential to use effective contraceptives from study entry through 90 days after study treatment. Participants with pregnant partners should use condoms during vaginal intercourse from study entry through 90 days after the last dose of the study treatment. Participants should refrain from sperm donation from study entry through 90 days after the last dose of study treatment (Camostat).
  • If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 24 weeks after investigational agent is administered. This would include oral contraceptives, implanted contraceptives, implanted contraceptives, intrauterine devices, and barrier methods.
  • If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for 24 weeks after investigational agent is administered (AZD7442 [IV], AZD7442 [IM], SAB-185).
  • If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 30 days after investigational agent is administered (SNG001).
  • If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 90 days after the last dose of treatment (Camostat).
  • If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for at least 48 weeks after the investigational agent is administered (BMS 986414+BMS 986413).

Exclusion Criteria:

  • History of or current hospitalization for COVID-19.
  • For the current SARS-CoV-2 infection, any positive SARS-CoV-2 nucleic acid or antigen tests from any respiratory tract specimen collected > 240 hours prior to study entry.
  • Current need for hospitalization or immediate medical attention.
  • Use of any prohibited medication listed in the protocol and/or use of systemic or inhaled steroids for the purpose of COVID-19 treatment (new or increased dose from chronic baseline) within 30 days prior to study.
  • Receipt of convalescent COVID-19 plasma or other antibody-based anti-SARS-CoV-2 treatment or prophylaxis at any time prior to study entry.
  • 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 or COVID-19 vaccines).
  • 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.
  • Currently pregnant or breastfeeding (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
  • In phase II, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).
  • Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections, or other overlying skin conditions or tattoos that would preclude the assessment of injection site reactions, per the discretion of the investigator (AZD7442 [IM]).
  • Inflammatory skin conditions that compromise the safety of subcutaneous (SC) injections, or other overlying skin conditions or tattoos that would preclude the assessment of infection site reactions, per the discretion of the investigator (BMS 986414+BMS 986413).
  • History of coagulopathy which, in the opinion of the investigator, would preclude IM injection, or use of oral or injectable anticoagulants (protocol provides more information on prohibited medications) (AZD7442 [IM]).
  • Use of or need for chronic supplemental oxygen (SNG001).
  • Known severe liver disease prior to enrollment (defined as ALT or AST > 5 times upper limit of normal or end stage liver disease with Child-Pugh Class C or Child-Pugh-Turcotte score ≥ 10) (Camostat).
  • Known severe kidney disease prior to enrollment (defined as estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m² or on renal-replacement therapy such as peritoneal dialysis or hemodialysis (Camostat)

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 Argentina,   Brazil,   Canada,   Mexico,   Philippines,   Puerto Rico,   South Africa,   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
  • Brii Biosciences Limited
  • AstraZeneca
  • Sagent Pharmaceuticals
  • Synairgen Research Ltd.
  • Bristol-Myers Squibb
  • SAb Biotherapeutics, Inc.
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 2021

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