ACTIV-2: A Study for Outpatients With COVID-19
ACTIV-2: A Study for Outpatients With COVID-19
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 and will have 28 days of intensive follow-up following study drug administration,
 followed by limited follow-up through 24 weeks. Study visits may be required after week 24
 depending on the study agent.
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. For infused agents, enrollment will
 be restricted to participants at higher risk of progression to severe COVID-19. Non-infused
 agents will be open to participants at both "higher" and "lower" risk of progression to
 severe COVID-19.

 For infused agents, the study begins with a phase II evaluation, followed by a transition
 into a larger Phase III evaluation for promising agents. Phase III evaluation is a
 continuation of the phase II trial for agents that meet study-defined criteria for further
 evaluation and for which sufficient investigational agent is available. An infused agent may
 also enter directly into phase III evaluation based on Trial Oversight Committee (TOC)
 assessments.

 For non-infused agents, the same phase II study will be undertaken as for infused agents.
 Following design of the phase III evaluation for non-infused agents in a subsequent version
 or amendment of the protocol these may also enter directly into phase III based on TOC
 assessments.

 Investigational agents will be selected by the 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.
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 8 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:

 -  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 24 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 24 hours of
 participating in the study). 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 severe
 COVID-19 (BRII-196/BRII-198, AZD7442 [IV]).

 -  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, CL135-LS+C144-LS).

 -  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 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 (C135-LS+C144-LS).

 Exclusion Criteria:

 -  History of or current hospitalization for COVID-19.

 -  For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular test from any
 respiratory tract specimen collected more than 10 days prior to study entry.

 -  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 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).

 -  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, C135-LS+C144-LS).

 -  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
 (C135-LS+C144-LS).

 -  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).

 -  Meet the protocol definition of being at "higher" risk of progression to sever
 COVID-19 (C135-LS+C144-LS).

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