NCT04518410

ACTIV-2: A Study for Outpatients With COVID-19

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

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 4,044 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 (monoclonal 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).

Conditions

• Coronavirus
• Covid19

Interventions

Type	Name	Description
BIOLOGICAL	bamlanivimab 7000mg	Administered by single IV infusion. Participants are no longer being randomized to this intervention.
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.
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.
DRUG	SNG001	1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device). Participants are no longer being randomized to this intervention.
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.
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). Participants are no longer being randomized to this intervention.
BIOLOGICAL	SAB-185 (3,840 Units/kg)	Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.
BIOLOGICAL	SAB-185 (10,240 Units/kg)	Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.
DRUG	CASIRIVIMAB + IMDEVIMAB	600 mg casirivimab and 600 mg imdevimab, administered together as single IV infusion as one-time dose at study entry. Participants are no longer being randomized to this intervention.
DRUG	Placebo for Bamlanivimab 7000mg	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for Bamlanivimab 700mg	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for BRII-196+BRII-198	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for SNG001	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). Participants are no longer being randomized to this intervention.
DRUG	Placebo for 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.
DRUG	Placebo for SAB-185 (low dose)	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for BMS-986414 + BMS-986413	Administered SC as 4 separate injections for one dose. Participants are no longer being randomized to this intervention.
DRUG	Placebo for AZD7442 (IV)	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for AZD7442 (IM)	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
DRUG	Placebo for SAB-185 (high dose)	Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
BIOLOGICAL	bamlanivimab 700mg	Administered by single IV infusion. Participants are no longer being randomized to this intervention.

Timeline

• Start date: 2020-08-19
• Primary completion: 2022-04-07
• Completion: 2023-06-20
• First posted: 2020-08-19
• Last updated: 2024-08-02
• Results posted: 2023-07-27

Locations

252 sites across 9 countries: United States, Argentina, Brazil, Canada, Guatemala, Mexico, Philippines, Puerto Rico, South Africa

Regulatory

• FDA-regulated drug study