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ACTIV-6: COVID-19 Study of Repurposed Medications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04885530
Recruitment Status : Recruiting
First Posted : May 13, 2021
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
National Center for Advancing Translational Science (NCATS)
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Susanna Naggie, MD, Duke University

Study Description
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Brief Summary:
The purpose of this study is to evaluate the effectiveness of repurposed medications (study drug(s) in reducing symptoms of non-hospitalized participants with mild to moderate COVID-19. Participants will receive either study drug or placebo. They will self-report any new or worsening symptoms or medical events they may experience while taking study drug or placebo. This study is intended to be all remote with no in person visits, unless the study team feels it is in the best interest of a participant to see them in person.

Condition or disease Intervention/treatment Phase
Covid19 Drug: Ivermectin Drug: Fluvoxamine Drug: Fluticasone Other: Placebo Phase 3

Detailed Description:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that first emerged in December 2019 and has since caused a global pandemic unseen in almost a century with respect to the number of cases and overall mortality. The clinical disease related to SARS-CoV-2 is referred to as Coronavirus Disease 2019 (COVID-19). Over 2020, advances were made for treatment of COVID-19 and several vaccinations have received emergency use authorization for prevention of SARS-CoV-2 infections. However, the pandemic continues to evolve with new variants and surges of infections in different regions of the world, requiring an ongoing evidence-generating platform, in particular for the treatment of COVID-19 infection in the outpatient setting.

This proposed platform protocol can serve as an evidence generating system for prioritized drugs repurposed from other indications with an established safety record and preliminary evidence of clinical efficacy for the treatment of COVID-19. The ultimate goal is to evaluate if repurposed medications can make participants feel better faster and reduce death and hospitalization.

This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within healthcare systems and in community settings where it can be integrated into routine COVID-19 testing programs and subsequent treatment plans. This platform protocol will enroll participants in an outpatient setting with a confirmed polymerase chain reaction (PCR) or antigen test for SARS-CoV-2.

Participants will be randomized to study drugs or placebo based on the arms that are actively enrolling at the time of randomization. Study drugs may be added or removed according to adaptive design and/or emerging evidence. When there are multiple study drugs available, randomization will occur based on appropriateness of each drug for the participant as determined by the study protocol and investigator and participant equipoise. Each participant will be required to randomize to at least one study drug versus placebo. The probability of placebo to treatment will remain the same regardless of eligibility decisions.

Eligible participants will be randomized (1:1), in a blinded fashion, to either the study drug arm or placebo arm in addition to standard of care. As additional study drugs are added, the randomization will be altered to leverage placebo data across arms. Participants will receive a complete supply study drug or placebo with the quantity depending on the study drug/placebo to which they are randomized.

All study visits are designed to be remote. However, screening and enrollment may occur in-person at sites and unplanned study visits may occur in-person or remotely, as deemed appropriate by the site investigator for safety purposes. Participants will be asked to complete questionnaires and report safety events during the study. Participants will be prompted by the online system to report safety events and these will be reviewed and confirmed via medical records and site staff, as necessary.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-Blind, Placebo-Controlled, Randomized Trial
Masking: Double (Participant, Care Provider)
Masking Description: The participant and study teams will know which study drug the participant is allocated to, but will be blinded to study drug versus placebo because they will be matching.
Primary Purpose: Treatment
Official Title: ACTIV-6: COVID-19 Outpatient Randomized Trial to Evaluate Efficacy of Repurposed Medications
Actual Study Start Date : June 8, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A - Ivermectin 400

Ivermectin - 7-mg tablets

Participant will be instructed to take a pre-specified number of tablets for 3 consecutive days based on their weight for a daily dose of approximately 300-400 µg/kg.

 Drug: Ivermectin
Each participant will receive a sufficient quantity of 7-mg tablets to be taken as directed based on their weight. The tablets are white, round, biconvex tablets with "123" over the scoring on one side. All packaging will be labeled to indicate that the product is for investigational use.
Other Name: Ivermectin Tablets
Placebo Comparator: Arm A - Placebo

Placebo -7mg tablets

Participant will be instructed to take a pre-specified number of tablets for 3 consecutive days based on their weight for a daily dose of approximately 300-400 µg/kg.

 Other: Placebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.
Experimental: Arm B - Fluvoxamine
Fluvoxamine will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days.
 Drug: Fluvoxamine
Fluvoxamine is a round golden 50 mg tablet that is scored on both sides - one side has "APO" and the other side has "F50" with a partial bisect. All packaging will be labeled to indicate that the product is for investigational use, administered at a dose of 50 mg, twice daily for 10 days.
Other Name: Fluvoxamine Maleate Tablets
Placebo Comparator: Arm B- Placebo
Placebo will be self-administered orally by each participant at a dose of 50 mg twice a day for 10 days.
 Other: Placebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.
Experimental: Arm C - Fluticasone
Fluticasone is a self-administered inhaled drug. Participants will self-administer 200 µg (1 blister) of fluticasone once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the study drug through the mouthpiece.
 Drug: Fluticasone
Fluticasone furoate is an inhaled powder drug product composed of fluticasone furoate. It is a synthetic trifluorinated corticosteroid that is insoluble in water. Fluticasone furoate is a white powder and will be provided in a two tone grey inhaler with a mouthpiece cover and separate foil blister strips. The inhaler will be packaged in a moisture-protective foil tray with a desiccant and a peelable lid.All packaging will be labeled to indicate that the product is for investigational use. Participants will self-administer 200 µg (1 blister) of fluticasone furoate once daily for 14 days.
Other Name: Fluticasone Furoate
Placebo Comparator: Arm C - Placebo
Placebo is a self-administered inhaled drug. Participants will self-administer 200 µg (1 blister) of placebo once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the placebo through the mouthpiece.
 Other: Placebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.
Experimental: Arm D - Ivermectin 600

Ivermectin - 7-mg tablets

Participant will be instructed to take a pre-specified number of tablets for 6 consecutive days based on their weight for a daily dose of approximately 400-600 µg/kg.

 Drug: Ivermectin
Each participant will receive a sufficient quantity of 7-mg tablets to be taken as directed based on their weight. The tablets are white, round, biconvex tablets with "123" over the scoring on one side. All packaging will be labeled to indicate that the product is for investigational use.
Other Name: Ivermectin Tablets
Placebo Comparator: Arm D - Placebo

Placebo -7mg tablets

Participant will be instructed to take a pre-specified number of tablets for 6 consecutive days based on their weight for a daily dose of approximately 400-600 µg/kg.

 Other: Placebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.


Outcome Measures
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Primary Outcome Measures :
  1. Number of hospitalizations as measured by patient reports. [ Time Frame: Up to 14 days ]
  2. Number of deaths as measured by patient reports [ Time Frame: Up to 14 days ]
  3. Number of symptoms as measured by patient reports [ Time Frame: Up to 14 days ]

Secondary Outcome Measures :
  1. Change in COVID Clinical Progression Scale [ Time Frame: Up to 28 days ]
    COVID Clinical Progression Scale is a scale of 0 to 8, with 0 being "No clinical or virological evidence of infection" to 8 being "death".

  2. Number of hospitalizations as measured by patient reports [ Time Frame: Up to 28 days ]
  3. Number of deaths as measured by patient reports [ Time Frame: Up to 28 days ]
  4. Number of Symptom Resolutions as measured by patient reports [ Time Frame: Up to 28 days ]
    Symptom resolution, defined as first of at least three consecutive days without symptoms

  5. Change in Quality of Life (QOL) as measured by the PROMIS-29 [ Time Frame: Baseline, Day 7, 14, 28, and 29 ]
    The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.

  6. Composite score of hospitalizations, urgent care visits, and emergency room visits as measured by patient reports [ Time Frame: Up to 28 days ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completed Informed Consent
  • Age ≥ 30 years old
  • Confirmed SARS-CoV-2 infection by any authorized or approved polymerase chain reaction (PCR) or antigen test collected within 10 days of screening
  • Two or more current symptoms of acute infection for ≤7 days. Symptoms include the following: fatigue, dyspnea, fever, cough, nausea, vomiting, diarrhea, body aches, chills, headache, sore throat, nasal symptoms, new loss of sense of taste or smell

Exclusion Criteria:

  • Prior diagnosis of COVID-19 infection (> 10 days from screening)
  • Current or recent (within 10 days of screening) hospitalization
  • Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo
  • Known contraindication(s) to study drug including prohibited concomitant medications
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04885530


Contacts
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Contact: Sybil Wilson 1-833-385-1880 sybil.wilson@duke.edu
Contact: Allison DeLong 919-668-6855 allison.delong@duke.edu

Locations
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Sponsors and Collaborators
Susanna Naggie, MD
National Center for Advancing Translational Science (NCATS)
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Susanna Naggie, MD Duke Clinical Research Institute
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Susanna Naggie, MD, Associate Professor of Medicine, Duke University
ClinicalTrials.gov Identifier: NCT04885530    
Other Study ID Numbers: Pro00107921
3U24TR001608-05W1 ( U.S. NIH Grant/Contract )
First Posted: May 13, 2021    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share this data after it has been de-identified. We will share data beginning around 6 months after publication and for up to 36 months afterward. Access will only be shared with those who have obtained prior IRB approval to be able to access this data.
Supporting Materials: Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Up to 36 months after publication
Access Criteria: Interested investigators will need to seek prior IRB approval before access to any data is granted.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Susanna Naggie, MD, Duke University:
SARS-CoV-2
COVID-19
ivermectin
Placebo
Duke University Health System
Outcomes
 Duke Clinical Research Institute
fluticasone
fluvoxamine
ACTIV 6
ACTIV
Additional relevant MeSH terms:
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COVID-19
Ivermectin
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Fluticasone
Xhance
 Fluvoxamine
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiparasitic Agents
Anti-Infective Agents
Anti-Anxiety Agents