COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol

COVID-19 Outpatient Pragmatic Platform Study (COPPS): A Pragmatic Multi-arm, Adaptive, Phase 2, Blinded, Randomized Placebo-controlled Platform Trial to Assess the Efficacy of Different Investigational Therapeutics in Reducing Time to Disease Resolution or Viral Load Cessation, as Compared to Standard Supportive Care in Outpatients With COVID-19

The overall objective of this study is to efficiently evaluate the clinical efficacy and safety of different investigational therapeutics among adults who have COVID-19 but are not yet sick enough to require hospitalization. The overall hypothesis is that through an adaptive trial design, potential effective therapies (single and combination) may be identified for this group of patients.

COVID-19 Outpatient Pragmatic Platform Study (COPPS) is a pragmatic platform protocol designed to evaluate COVID-19 treatments by assessing their ability to reduce viral shedding (Viral Domain) or improve clinical outcomes (Clinical Domain). To be included into the platform, every investigational product will collect data for both Domain primary endpoints. Individual treatments to be evaluated in the platform will be described in separate sub-protocols.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Camostat; Drug: Acebilustat

Detailed Description

The platform study allows investigational products with objectives either: evaluating viral shedding (Virology Domain); and COVID-19 related Clinical Outcomes (Clinical Domain).

The primary objective for investigational products within the Viral Domain is:

A. To evaluate the efficacy of each therapeutic intervention in addition to standard supportive care (SSC) compared with SSC in reducing viral shedding of SARS-CoV-2 virus in outpatients with COVID-19 disease.

The primary objective for investigational products within for the Clinical Domain is:

B. To evaluate the efficacy of each therapeutic intervention in addition to SSC as compared to SSC in improving sustained clinical outcomes in outpatients with COVID-19 disease.

Secondary objectives are:

1. The objective of the non-assigned domain an investigational product is under.

   1. If under Clinical Domain, reduction in viral shedding.
   2. If under Viral Domain, time to sustained resolution of symptoms.
2. To evaluate the efficacy of each therapeutic intervention in reducing SARS-CoV-2 related hospitalizations, ED visits, or death in outpatients with COVID-19 disease.
3. To assess the development of antibodies against SARS-CoV-2
4. To evaluate the safety and tolerability of each therapeutic intervention compared with placebo (supportive care).

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Pleasanton, California, United States, 94588
      • ValleyCare Medical Center
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Outpatient setting
2. Age ≥ 18 years and ≤ 80 years at the time of the assessment
3. Able and willing to understand the study, adhere to all study procedures, and provide written informed consent
4. Initial diagnosis of COVID-19 disease as defined by an FDA-cleared molecular diagnostic assay positive for SARS-CoV-2 with no more than 72 hours from the initial swab used in the diagnosis to the time of commencing informed consent.
5. At baseline, at least two symptoms should have mild or higher severity score, where at least one of the mild symptoms is not cough, fatigue, or loss of smell/taste OR at least one symptom has a moderate or higher severity score on the COVID Outpatient Symptom Scale (COSS).
6. Participant's COVID-19 related symptom onset occurred within 7 days prior to time of randomization.
7. Other inclusion criteria specific to the investigational product that may, in the eyes of the investigator, be deemed necessary.

Exclusion Criteria:

1. At screening, the participant needs to be admitted to the hospital or is being evaluated for potential admission.
2. Previous use of experimental drugs that may be active against COVID-19 in the eyes of the investigators.
3. Participant yields a positive urine pregnancy test at screening.

4. Participant is using adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers).

   NOTE: Treatment of study participants following institutional COVID-19 treatment policies or guidelines, including the use of immunomodulatory medications, is permitted. This excludes treatment with agents that have the potential for direct antiviral activity, including convalescent plasma and NO, and co-enrollment into other clinical studies that evaluate investigational agents for COVID-19.

5. Participant has a serious chronic disease (e.g., uncontrolled human immunodeficiency virus [HIV], cancer requiring chemotherapy within the preceding 6 months, and/or moderate or severe hepatic insufficiency).
6. Has renal insufficiency including severe renal impairment and ESRD and/or requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
7. Has liver impairment greater than Child Pugh A.
8. Has a history of alcohol or drug abuse in the previous 6 months.
9. Has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year.
10. Has taken another investigational drug within the past 30 days.
11. Is deemed by the Investigator to be ineligible for any reason.
12. Additional exclusions may pertain to specific drugs as described in study-specific protocols.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acebilustat; Participants are randomized to receive either active acebilustat or matching placebo for 28 days.	Drug: Acebilustat; 100 mg capsule administered orally once daily
Experimental: Camostat; Participants are randomized to receive either active camostat or matching placebo for 10 days.	Drug: Camostat; 200 mg (2 x 100 mg tablet) administered orally four times daily (800 mg total daily dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Clinical Domain: Time-to-sustained-resolution	Time from randomization to sustained symptom resolution assessed over a 28-day period. Resolution is defined as the first day where no symptoms are self-reported on all succeeding days through and including day 28, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none.	28 days
For Viral Domain: Change in Viral Shedding	Change in shedding of SARS-CoV-2 virus through day 10 attained from self-collected nasal swab. Viral load (nucleic acid) was assessed by RT-PCR Ct over time, and is reported here as the average change in Ct values per day. Cycle threshold (Ct) denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to ~2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Viral Cessation	Defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs.	28 days
Time to First Resolution	Defined as the first study day where no symptoms are self-reported, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none.	28 days
Time to Full Resolution	Defined as the study day where no symptoms are first self-reported.	28 days
Number of Participants With SARS-CoV-2 Related Hospitalizations, Emergency Department (ED) Visits, or Death in Outpatients With COVID-19 Disease.		28 days
Number of Participants That Developed Antibodies to SARS-CoV-2		28 days

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Chaitan Khosla, PhD, Stanford University; Principal Investigator: Upinder Singh, MD, Stanford University; Principal Investigator: Manisha Desai, PhD, Stanford University; Principal Investigator: Yvonne Maldonado, MD, Stanford University; Principal Investigator: Haley Hedlin, PhD, Stanford University

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Bunning B, Hedlin H, Purington N, Sundaram V, Kapphahn K, Weng Y, Cunanan K, Maldonado Y, Singh U, Khosla C, O'Hara R, Nicolls M, Springman E, Parsonnet J, Rogers A, Levitt J, Desai M. The COVID-19 Outpatient Pragmatic Platform Study (COPPS): Study design of a multi-center pragmatic platform trial. Contemp Clin Trials. 2021 Sep;108:106509. doi: 10.1016/j.cct.2021.106509. Epub 2021 Jul 16.
• Levitt JE, Hedlin H, Duong S, Lu D, Lee J, Bunning B, Elkarra N, Pinsky BA, Heffernan E, Springman E, Moss RB, Bonilla HF, Parsonnet J, Zamanian RT, Langguth JJ, Bollyky J, Khosla C, Nicolls MR, Desai M, Rogers AJ. Evaluation of acebilustat, a selective inhibitor of leukotriene B4 biosynthesis, for treatment of outpatients with mild-moderate COVID-19 disease: A randomized, double-blind, placebo- controlled Phase 2 trial. Clin Infect Dis. 2023 Mar 30:ciad187. doi: 10.1093/cid/ciad187. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Actual): May 3, 2022
• Study Completion (Actual): February 2, 2023

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Outpatient; Master Protocol
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Camostat
• Other Study ID Numbers: COPPS-Master Protocol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No