ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)

Sponsor

Susanna Naggie, MD (Other)

Overall Status

Completed

CT.gov ID

NCT05736874

Collaborator

National Center for Advancing Translational Sciences (NCATS) (NIH), Vanderbilt University Medical Center (Other)

1,341

Enrollment

Locations

Arms

9.4

Actual Duration (Months)

15.4

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Prior and current drug arms are listed on clinicaltrials.gov and will be updated with the activation of any new drug arms. This protocol was originally registered under NCT04885530. Per recent guidance on reporting master protocol research programs (MPRPs), a separate record for Arm C was created.

Condition or Disease	Intervention/Treatment	Phase
Covid19	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

Study Type:

Interventional

Actual Enrollment :

1341 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-Blind, Placebo-Controlled, Randomized TrialDouble-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 :

Aug 6, 2021

Actual Primary Completion Date :

Mar 17, 2022

Actual Study Completion Date :

May 18, 2022

Arms and Interventions

Arm	Intervention/Treatment
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 inhaled agent. 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.

Arm

Intervention/Treatment

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 inhaled agent. 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.

Outcome Measures

Primary Outcome Measures

Number of hospitalizations as measured by patient reports. [Up to 28 days]
Number of deaths as measured by patient reports [Up to 28 days]
Number of symptoms as measured by patient reports [Up to 28 days]

Secondary Outcome Measures

Change in COVID Clinical Progression Scale [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".
Number of hospitalizations as measured by patient reports [Up to 28 days]
Number of deaths as measured by patient reports [Up to 28 days]
Number of Symptom Resolutions as measured by patient reports [Up to 28 days]
Symptom resolution, defined as first of at least three consecutive days without symptoms
Change in Quality of Life (QOL) as measured by the PROMIS-29 [Baseline, Day 7, 14, 28, and 90]
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.
Composite score of hospitalizations, urgent care visits, and emergency room visits as measured by patient reports [Up to 28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Current use 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*

[*If only one study drug appendix is open at the time of enrollment. If multiple study drug appendices are open, a participant may opt-out of any study drug appendix or be excluded from any study drug appendix based on contraindications listed in the study drug appendix, current use of study drug, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study drug appendices.]

Arm-specific exclusion criteria

Severe hypersensitivity to milk proteins
Currently prescribed or use within 30 days of inhaled or systemic steroids
Moderate to severe hepatic impairment, defined as Child-Pugh B or C
Nursing mothers
Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lamb Health, LLC	Gilbert	Arizona	United States	85298
2	First Care Medical Clinic	Mesa	Arizona	United States	85203
3	Trident Health Center	Peoria	Arizona	United States	85382
4	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
5	Assuta Family Medical Group APMC	North Hollywood	California	United States	91606
6	Stanford	Palo Alto	California	United States	94304
7	Doctors Medical Group of Colorado Springs, P.C.	Colorado Springs	Colorado	United States	80917
8	Pine Ridge Family Medicine Inc.	Colorado Springs	Colorado	United States	80924
9	Tabitha B. Fortt, M.D., LLC	Stamford	Connecticut	United States	06905
10	George Washington University Hospital	Washington	District of Columbia	United States	20037
11	Lupus Foundation of Gainesville	Gainesville	Florida	United States	32606
12	University of Florida Health	Gainesville	Florida	United States	32611
13	University of Florida-JAX-ASCENT	Jacksonville	Florida	United States	32209
14	AMRON Vitality and Wellness Center, LLC	Jacksonville	Florida	United States	32244
15	Sunshine Walk In Clinic	Lake Mary	Florida	United States	32746
16	Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
17	Jackson Memorial Hospital	Miami	Florida	United States	33136
18	University of Miami	Miami	Florida	United States	33136
19	Well Pharma Medical Research	Miami	Florida	United States	33173
20	Innovation Clinical Trials Inc.	Palmetto Bay	Florida	United States	33157
21	Lice Source Services Plantation	Plantation	Florida	United States	33313
22	Premier Health	Saint Petersburg	Florida	United States	33707
23	Tallahassee Memorial Hospital	Tallahassee	Florida	United States	32308
24	Tampa General Hospital	Tampa	Florida	United States	33606
25	UF Health Precision Health Research	The Villages	Florida	United States	32159
26	Emory Healthcare	Atlanta	Georgia	United States	30322
27	Essential Medical Care, Inc.	College Park	Georgia	United States	30349
28	David Kavtaradze MD, Inc.	Cordele	Georgia	United States	31015
29	Elite Family Practice	Douglasville	Georgia	United States	30134
30	Christ the King Health Care, P.C.	Loganville	Georgia	United States	30052
31	Miller Family Practice, LLC	Macon	Georgia	United States	31201
32	Olivo Wellness Medical Center	Chicago	Illinois	United States	60618
33	NorthShore Medical Group	Evanston	Illinois	United States	60201
34	Advanced Medical Care, Ltd	Lake Zurich	Illinois	United States	60047
35	Franciscan Health Michigan City	Michigan City	Indiana	United States	46360
36	Del Pilar Medical and Urgent Care	Mishawaka	Indiana	United States	46545
37	University of Kansas - Wichita	Wichita	Kansas	United States	67214
38	A New Start II, LLC	Central City	Kentucky	United States	42330
39	University Medical Center- New Orleans	New Orleans	Louisiana	United States	70112
40	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
41	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287-1900
42	Jadestone Clinical Research, LLC	Rockville	Maryland	United States	20855
43	Boston Medical Center	Boston	Massachusetts	United States	02118
44	Health Quality Primary Care	Lawrence	Massachusetts	United States	01843
45	Ananda Medical Clinic	Dearborn	Michigan	United States	48124
46	GFC of Southeastern Michigan, PC	Detroit	Michigan	United States	48202
47	Romancare Health Services	Detroit	Michigan	United States	48206
48	Essentia Health	Duluth	Minnesota	United States	55805
49	University of Minnesota	Minneapolis	Minnesota	United States	55455
50	University of Missouri - Columbia	Columbia	Missouri	United States	65212
51	Comprehensive Pain Management and Endocrinology	Henderson	Nevada	United States	89052
52	Focus Clinical Research Solutions	Bayonne	New Jersey	United States	07002
53	Raritan Bay Primary Care & Cardiology Associates	Matawan	New Jersey	United States	07747
54	Mediversity Healthcare	Turnersville	New Jersey	United States	08012
55	Geriatrics and Medical Associates	Clinton	New York	United States	13323
56	Weill Cornell Medical College	New York	New York	United States	10065
57	Spinal Pain and Medical Rehab, PC	Yonkers	New York	United States	10701
58	Vaidya MD PLLC	Clayton	North Carolina	United States	27520
59	Maria Medical Center, PLLC	Dunn	North Carolina	United States	28334
60	Duke Clinical Research Institute	Durham	North Carolina	United States	27701
61	Duke University Medical Center	Durham	North Carolina	United States	27710
62	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27151
63	Diabetes and Endocrinology Assoc. of Stark County	Canton	Ohio	United States	44718
64	University of Cincinnati	Cincinnati	Ohio	United States	45267
65	TriHealth, Inc	Montgomery	Ohio	United States	45242
66	The Heart and Medical Center	Durant	Oklahoma	United States	74701
67	Hugo Medical clinic	Hugo	Oklahoma	United States	74743
68	Bucks County Clinical Research	Morrisville	Pennsylvania	United States	19067
69	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
70	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
71	Medical University of South Carolina	Charleston	South Carolina	United States	29403
72	Clinical Trials Center of Middle TN	Franklin	Tennessee	United States	37067
73	Rapha Family Wellness	Hendersonville	Tennessee	United States	37075
74	Medical Specialists of Knoxville	Knoxville	Tennessee	United States	37938
75	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37203
76	Express Family Clinic	Allen	Texas	United States	75013
77	Texas Tech University Health Sciences Center	El Paso	Texas	United States	79905
78	Texas Health Physicians Group	Fort Worth	Texas	United States	76107
79	Highlands Medical Associates, P.A.	Highlands	Texas	United States	77562
80	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
81	Family Practice Doctors P.A.	Humble	Texas	United States	77338
82	Vytalus Medical Group	Humble	Texas	United States	77338
83	Texas Health Physicians Group	Irving	Texas	United States	75039
84	University Diagnostics and Treatment Clinic	Pasadena	Texas	United States	77504
85	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
86	Jeremy W. Szeto, D.O., P.A.	Sugar Land	Texas	United States	77479
87	University of Virginia	Charlottesville	Virginia	United States	22903