COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol

Study Overview
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Brief Summary
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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.

Detailed Description
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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: The objective of the non-assigned domain an investigational product is under. If under Clinical Domain, reduction in viral shedding. If under Viral Domain, time to resolution of symptoms. 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. To assess the development of antibodies against SARS-CoV-2 To evaluate the safety and tolerability of each therapeutic intervention compared with placebo (supportive care).

Official Title
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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

Conditions
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Covid19

Intervention / Treatment
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* Drug: Acebilustat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient setting Age ≥ 18 years and ≤ 80 years at the time of the assessment Able and willing to understand the study, adhere to all study procedures, and provide written informed consent 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. 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). Participant's COVID-19 related symptom onset occurred within 7 days prior to time of randomization. Other inclusion criteria specific to the investigational product that may, in the eyes of the investigator, be deemed necessary. Exclusion Criteria: At screening, the participant needs to be admitted to the hospital or is being evaluated for potential admission. Previous use of experimental drugs that may be active against COVID-19 in the eyes of the investigators. Participant yields a positive urine pregnancy test at screening. 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. 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). Has renal insufficiency including severe renal impairment and ESRD and/or requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Has liver impairment greater than Child Pugh A. Has a history of alcohol or drug abuse in the previous 6 months. Has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year. Has taken another investigational drug within the past 30 days. Is deemed by the Investigator to be ineligible for any reason. Additional exclusion criteria for acebilustat protocol: Patient has abnormal liver enzyme tests at screening, including AST or ALT ≥3 × the upper limit of normal (ULN) or total bilirubin >1.25 × ULN at Screening (patients with known Gilbert's syndrome can be included with bilirubin >1.25 × ULN). Patient is pregnant or breastfeeding. Patients with baseline ALT >1.5 × ULN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acebilustat<br>Participants are randomized to receive acebilustat for 28 days. | Drug: Acebilustat<br>* 100 mg capsule administered orally once daily<br>|
| Placebo Comparator: Matching Placebo<br>Participants are randomized to receive placebo to match acebilustat for 28 days. | Drug: Placebo<br>* Placebo to match acebilustat administered orally once daily<br>|

What is the study measuring?
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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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For the 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Outpatient