Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 and conducted an any US clinic or laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent or any non-US 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.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Bamlanivimab
Administered by IV infusion.
  • 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 names:
    • LY3819253
Experimental
BRII-196/BRII-198
Administered by IV infusion.
  • 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.
Experimental
AZD7442 (IV)
Administered by IV infusion.
  • 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 names:
    • AZD8895 + AZD1061
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
  • Drug: Placebo (IV)
    Commercially available 0.9% sodium chloride solution.
Experimental
SNG001
Administered by inhalation.
  • Drug: SNG001
    1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device).
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
  • 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).
Experimental
AZD7442 (IM)
Administered by IM injection.
  • 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 names:
    • AZD8895 + AZD1061
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
  • 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.
Experimental
Camostat
Administered as oral tablets.
  • 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
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
  • Drug: Placebo (oral tablet)
    200 mg (2 x 100 mg) film-coated tablets administered orally every 6 hours for 7 days.
Experimental
BMS 986414 + BMS 986413
Administered as subcutaneous (SC) injections.
  • 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 names:
    • C135-LS + C144-LS
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
  • Drug: Placebo (SC injections)
    Administered SC as 4 separate injections for one dose.
Experimental
SAB-185 (Lower dose)
Administered by IV infusion.
  • Biological: SAB-185 (3,840 Units/kg)
    Administered by IV infusion as single dose.
    Other names:
    • Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)
Experimental
SAB-185 (Higher dose)
Administered by IV infusion.
  • Biological: SAB-185 (10,240 Units/kg)
    Administered by IV infusion as single dose.
    Other names:
    • Anti-SARS-CoV-2 Human Immunoglobulin Intravenous (Tc bovine-derived)
Active Comparator
Casirivimab + Imdevimab (Phase III only)
Administered by IV infusion
  • 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

Recruiting Locations

Vanderbilt Therapeutics Clinical Research (Site 1013), Vanderbilt Health One Hundred Oaks, 719 Thompson Ln., Ste 47183
Nashville, Tennessee 37204-4718
Contact:
Beverly Woddward
615-936-8516
beverly.o.woodward@vumc.org

More Details

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

Study Contact

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).

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.