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

• ClinicalTrials.gov Identifier: NCT04662060
• Recruitment Status: Active, not recruiting
• First Posted: December 10, 2020
• Last Update Posted: May 27, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Tracking Information

• First Submitted Date: December 8, 2020
• First Posted Date: December 10, 2020
• Last Update Posted Date: May 27, 2022
• Actual Study Start Date: April 23, 2021
• Actual Primary Completion Date: May 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2021)

For Clinical Domain: Time-to-sustained-resolution [ Time Frame: 28 days ]

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.

Original Primary Outcome Measures (submitted: December 9, 2020)

• For Viral Domain:Time until cessation of shedding of SARS-CoV-2 virus [ Time Frame: 28 days ]
  Defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs
• For Clinical Domain: Time from randomization to sustained symptom resolution assessed over a 28-day period [ Time Frame: 28 days ]
  Resolution is defined as the first study day where no symptoms are self-reported for 48 hours, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none. Participants who never experienced resolution will be censored at their last survey completion day.

Current Secondary Outcome Measures (submitted: April 8, 2021)

• For the Viral Domain: Change in Viral Shedding [ Time Frame: 10 days ]
  Change in shedding of SARS-CoV-2 virus through day 10 attained from self-collected nasal swab RT-PCR data after transformation using a referenced standard curve.
• Time to viral cessation [ Time Frame: 28 days ]
  Defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs.
• Time to first resolution [ Time Frame: 28 days ]
  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.
• Time to full resolution [ Time Frame: 28 days ]
  Defined as the study day where no symptoms are first self-reported.
• Indicator of SARS-CoV-2 related hospitalizations, ED visits, or death in outpatients with COVID-19 disease. [ Time Frame: 28 days ]
• Indicator participant has developed antibodies to SARS-CoV-2 [ Time Frame: 28 days ]

Original Secondary Outcome Measures (submitted: December 9, 2020)

• Time to first resolution [ Time Frame: 28 days ]
  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.
• Indicator of SARS-CoV-2 related hospitalizations, ED visits, or death in outpatients with COVID-19 disease. [ Time Frame: 28 days ]
• Indicator participant has developed antibodies to SARS-CoV-2 [ Time Frame: 28 days ]
• Time to event from randomization to worsening of symptoms or disease progression [ Time Frame: 28 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Acebilustat Sub-Protocol
• Official Title: 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

Brief Summary

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

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 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Covid19

Intervention

• Drug: Acebilustat
  100 mg capsule administered orally once daily
• Drug: Placebo
  Placebo to match acebilustat administered orally once daily

Study Arms

• Experimental: Acebilustat
  Participants are randomized to receive acebilustat for 28 days.
  Intervention: Drug: Acebilustat
• Placebo Comparator: Matching Placebo
  Participants are randomized to receive placebo to match acebilustat for 28 days.
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 9, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2022
• Actual Primary Completion Date: May 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Additional exclusion criteria for acebilustat protocol:

1. 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).
2. Patient is pregnant or breastfeeding.
3. Patients with baseline ALT >1.5 × ULN.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04662060
• Other Study ID Numbers: COPPS-Acebilustat
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Angela Rogers, MD; Stanford University
• Principal Investigator: Joseph Levitt, MD, MS; Stanford University

• PRS Account: Stanford University
• Verification Date: May 2022