ACTIV-6: COVID-19 Study of Repurposed Medications

Purpose

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. Prior and current drug arms are listed on clinicaltrials.gov and will be updated with the activation of any new drug arms. Each study arm will also have its own clinicaltrials.gov entry and will include "Pro00107921" in the Unique Protocol ID. Pro00107921_A - Arm D (Ivermectin 400) - NCT05736861; Pro00107921_B - Arm B (Fluvoxamine) - NCT05890586; Pro00107921_C - Arm C (Fluticasone) - NCT05736874; Pro00107921_D - Arm D (Ivermectin 600) - NCT05894538; Pro00107921_E - Arm E (Fluvoxamine 100) - NCT05894564; Pro00107921_F - Arm F (Montelukast) - NCT05894577; Pro00107921_G - Arm G (Metformin) - NCT06042855.

Condition

  • Covid19

Eligibility

Eligible Ages
Over 30 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

  • Current or recent (within 10 days of screening) hospitalization for COVID-19 infection - Current or planned participation in another interventional trial to treat COVID-19, at the discretion of the study principal investigator (PI) - Current or recent use (within the last 14 days) of study drug or study drug/device combination - Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo - Known contraindication(s) to study drug including prohibited concomitant medications - Previous or current enrollment in the ACTIV-6 trial

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Double-Blind, Placebo-Controlled, Randomized Trial
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • Ivermectin Tablets
Placebo Comparator
Arm A - Placebo 		Placebo - appearance and size matched to active study drug. Participant will be instructed to take a pre-specified number of tablets for 3 consecutive days based on their weight, matched to active study drug dosing.
  • 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 names:
    • Fluvoxamine Maleate Tablets
Placebo Comparator
Arm B- Placebo 		Placebo - appearance and size matched to active study drug. Placebo will be self-administered orally by each participant 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 names:
    • Fluticasone Furoate
Placebo Comparator
Arm C - Placebo 		Placebo is a self-administered by inhalation. Participants will self-administer 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 names:
    • Ivermectin Tablets
Placebo Comparator
Arm D - Placebo 		Placebo - appearance and size matched to active study drug. Participant will be instructed to take a pre-specified number of tablets for 6 consecutive days based on their weight, matched to active study drug dosing.
  • 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 E - Fluvoxamine 100 		Fluvoxamine will be self-administered orally by each participant at a dose of 50 mg twice a day for 1 day, followed by a dose of 100 mg twice a day for 12 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 names:
    • Fluvoxamine Maleate Tablets
Placebo Comparator
Arm E - Placebo 		Placebo - appearance and size matched to active study drug. Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.
  • 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 F - Montelukast 		Montelukast will be self-administered orally by each participant at a dose of 10 mg once a day for 14 days.
  • Drug: Montelukast
    Montelukast sodium is a white to off-white powder. The 10 mg montelukast tablets are beige, rounded square-shaped, biconvex, film-coated tablets. Each tablet contains 10.4 mg of montelukast sodium, which is equivalent to 10 mg montelukast. All packaging will be labeled to indicate that the product is for investigational use.
Placebo Comparator
Arm F - Placebo 		Placebo - appearance and size matched to active study drug. Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.
  • 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 G - Metformin 		Metformin IR tablets will be self-administered orally according to the following dosing schedule: - 500 mg on Day 1; - 500 mg in the morning and 500 mg in the evening on Day 2 through Day 5; and - 500 mg in the morning and 2 x 500 mg (a total of 1000 mg) in the evening on Day 6 through Day 14.
  • Drug: Metformin
    Metformin IR tablets contain the active metformin hydrochloride and inactive ingredients including povidone and magnesium stearate. Commercially available metformin 500 mg tablets will be provided.
Placebo Comparator
Arm G - Placebo 		Placebo - appearance and size matched to active study drug. Placebo will be self-administered orally by each participant, with number of tablets matched to active study drug dosing.
  • 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.

Recruiting Locations

More Details

NCT ID
NCT04885530
Status
Completed
Sponsor
Susanna Naggie, MD

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.