Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion
Principal Investigator
by David Smith, MD, MAS
Photo of David Smith
David Smith

Description

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 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.

Official Title

Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)

Details

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. Version 6.0 of the protocol restricts enrollment to agents in phase II to participants at lower risk of progression to severe COVID-19, regardless of the mode of administration of the agent. The current phase III evaluation will continue as a placebo-controlled evaluation of the one agent that has previously been approved for full phase III evaluation by the Trial Oversight Committee (TOC) and will continue to include only participants who are at higher risk of progression to severe COVID-19. The design of the phase III evaluation for future agents will be developed in a subsequent version of the protocol and will include an active-controlled comparator instead of a placebo control. 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.

Keywords

Coronavirus Covid19 COVID-19 COVID 19 Coronaviridae Infections Coronavirus Infections RNA Virus Infections Virus Diseases Nidovirales Infections SARS-CoV-2 SARS Coronavirus ACTIV-2 ACTIV2 Gabexate Immunoglobulins Immunoglobulins, Intravenous Antibodies Camostat bamlanivimab BRII-196/BRII-198 AZD7442 (IV) AZD7442 (IM) SNG001 SAB-185 (3,840 Units/kg) SAB-185 (10,240 Units/kg) SAB-185 (Lower dose) SAB-185 (Higher dose)

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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).
  • 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).

You CAN'T join if...

  • 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).
  • In phase II, meeting the protocol definition of being at "higher risk of progression to severe COVID-19" (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)

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

Locations

  • University of California San Diego (Site 1160), 9350 Campus Point Drive, Perlman Cancer Cancer accepting new patients
    La Jolla California 92037 United States
  • University of California San Diego (Site 1002), 220 Dickinson Street accepting new patients
    San Diego California 92103 United States
  • VA San Diego Health System (Stie 1127), 3350 La Jolla accepting new patients
    San Diego California 92161-0002 United States

Lead Scientist at UCSD

  • David Smith, MD, MAS
    Davey Smith, MD, MAS, is an infectious disease specialist and translational research virologist. In his translational research, he uses basic science techniques to answer clinically relevant questions. Dr. Smith's primary research involves both figuring out how to stop the transmission of HIV and curing HIV, and he has published over 200 scientific publications in these areas.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
A Participant's Guide to Clinical Trials (NIAID) Find a Clinical Trial (NIAID) Clinical Trials at NIAID National Institute for Allergy and Infectious Diseases (NIAID) NIH: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
ID
NCT04518410
Phase
Phase 2/3
Study Type
Interventional
Last Updated