ACTG Adds Four Promising New Therapies To ACTIV-2 Outpatient Treatment Study

The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the addition of four new promising therapies to the COVID-19 outpatient treatment study, ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial. These additional agents represent a variety of treatment modalities, including a rapid infusion, an intramuscular injection, an inhalant, and an oral agent. ACTIV-2 includes both phase 2 and phase 3 evaluations of multiple investigational agents for treating early, symptomatic COVID-19 in a single trial. For information about enrolling in the trial, please visit the study website.

“ACTIV-2’s design enables us to simultaneously evaluate a range of treatment options and we are excited to identify agents that can treat COVID-19 early to improve symptoms, reduce transmission, and prevent progression of disease,” said ACTG Chair Judith Currier, MD, MSc, University of California, Los Angeles (UCLA). “The ACTG aims to advance as many successful therapeutics as we can, making the treatment of COVID-19 simple and accessible.”

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ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents against placebo within the same trial infrastructure. In addition to studying the safety and efficacy of these investigational therapies, ACTIV-2 also aims to determine whether they are able to decrease viral shedding, thereby potentially preventing transmission of SARS-CoV-2 (the virus that causes COVID-19). The new agents, which will be evaluated in phase 2 studies among non-hospitalized adults with COVID-19 are:

• AZD7442 (AstraZeneca): a combination of two monoclonal antibodies (AZD8895 and AZD1061) that will be studied as both an infusion administered over 15 minutes and an intramuscular injection

• SNG001 (Synairgen): a nebulized formulation of beta interferon that will be studied as an inhalant

• Camostat (Sagent Pharmaceuticals): an orally administered serine protease inhibitor that inhibits viral entry by blocking a host cell protease

ACTIV-2 was developed and launched and has proceeded on an unprecedented timeline. The ACTG received approval to develop an adaptive master platform trial for non-hospitalized individuals with COVID-19 in May 2020 and enrolled the first participant less than 15 weeks later. Following intensive efforts to set up outpatient treatment sites, there are now 104 active U.S. sites, which are enrolling briskly. In addition to the four new therapies announced today, ACTIV-2 is currently conducting a phase 2 study of BRII-196 and BRII-198 (a combination of monoclonal antibodies administered through infusion) and has completed a phase 2 study of bamlanivimab (a single monoclonal antibody, also administered through infusion).

To qualify for ACTIV-2, participants must have tested positive for SARS-CoV-2 in the outpatient setting within 10 days and started experiencing symptoms within eight days of enrolling. Participants eligible for the AZD7442 infusion study will have a risk factor that puts them at higher risk of progressing to severe COVID-19, including being age 60 or older, being a current smoker, or having one of the following conditions: chronic lung, kidney, or liver disease; obesity; hypertension; cardiovascular disease; diabetes; or current cancer or immunosuppression. Participants eligible for the other agents may be at higher or lower risk for progressing to severe COVID-19.

ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response - Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

New ACTIV-2 Agents

Each of the new agents is being evaluated in a phase 2 study that will randomize 110 participants to receive the investigational agent and 110 to receive placebo.

• AZD7442, developed by AstraZeneca, is a combination of two monoclonal antibodies (AZD8895 and AZD1061) that is being studied as both a rapid (15-minute) infusion and an intramuscular injection. Both monoclonal antibodies were created from antibodies made by individuals who recovered from COVID-19 and target the spike protein of SARS-CoV-2. In the infusion study, participants will receive one 300 mg infusion of AZD7442 (150 mg of AZD8895 plus 150 mg of AZD1061) or placebo. In the injection study, participants will receive 600 mg of AZD7442 as two separate intramuscular injections administered on the same day (300 mg of AZD8895 and 300 mg of AZD1061) or placebo. Rachel Bender-Ignacio, MD, MPH (University of Washington) is leading the injection study and David Alain Wohl, MD (University of North Carolina or UNC) is leading the infusion study.

• SNG001,developed by Synairgen, is a nebulized formulation of beta interferon that is being studied as an inhalant. SNG001 will be self-administered as a nebulized dose (15.6 MIU) that participants will inhale once daily for 14 days. Participants will be trained to use the nebulizer device by study staff and will take all doses at home. ACTIV-2 is the first U.S. study to evaluate SNG001 among non-hospitalized people with COVID-19. The study is being led by Billy Fischer, M.D. (UNC), Upi Singh, MD (Stanford University), and Prasanna Jagannathan, MD (Stanford University).

• Camostat, provided by Sagent Pharmaceuticals (a Nichi-Iko Group Company), is an orally administered protease inhibitor that will be dosed as 200 mg every six hours for seven days. Camostat inhibits TMPRSS2, a host cell protease that facilitates SARS-CoV-2 binding and entry into the host cell. Participants will take the first dose of Camostat at enrollment and subsequent doses at home. The study is being led by Jonathan Li, MD, MMSc (Brigham and Women’s Hospital Therapeutics, Harvard Medical School) and Nikolaus Jilg, MD, PhD (Massachusetts General Hospital, Harvard Medical School).

“With the addition of these agents, ACTIV-2 is now able to evaluate treatments for people across a range of risk for progressing to severe COVID-19, thereby broadening the potential population who may be helped by these treatments,” said Kara W. Chew, MD, MS, UCLA. “While the rollout of COVID-19 vaccines is a tremendous milestone, given the unprecedented number of COVID-19 cases around the world, we remain in urgent need of treatment options. We are hopeful that ACTIV-2 will provide some of the solutions we need to effectively counter the pandemic and mitigate complications of COVID-19 for the many who are affected.”

ACTIV-2 is led by Dr. Chew and Davey Smith, MD, University of California, San Diego (protocol chairs) and Dr. Wohl and Eric S. Daar, MD, Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, MD, UNC.

“We are very pleased that ACTIV-2 has added such a diverse range of treatment options to the study,” said Orbit Clanton, a member of the ACTIV-2 community advisory board (CAB) and co-chair of the ACTG’s global CAB. “The CAB’s focus has been on ensuring that the study provides real world solutions to the profound challenges presented by COVID-19. Pursuing a variety of treatment types through ACTIV-2’s unique study design is an important part of that mission.”

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