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CD24Fc as a Non-antiviral Immunomodulator in COVID-19 Treatment (SAC-COVID)

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ClinicalTrials.gov Identifier: NCT04317040
Recruitment Status : Not yet recruiting
First Posted : March 20, 2020
Last Update Posted : March 23, 2020
Sponsor:
Information provided by (Responsible Party):
OncoImmune, Inc.

Brief Summary:

The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe COVID 19 and absolute lymphocyte counts ≤ 800/mm^3 in peripheral blood.

Arm A: CD24Fc/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via IV infusion on Day 1. Total of 230 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. Serum cytokine IL-6 level will be used as stratification factor in randomization. All subjects will be treated with the best available treatment. The follow up period is 15 days.


Condition or disease Intervention/treatment Phase
Severe Coronavirus Disease (COVID-19) Drug: CD24Fc Drug: Placebo Phase 3

Detailed Description:

As the newest global medical emergency, the COVID-19 (diagnosed SARS-CoV2 infection with lung involvement) exhibits features that are unlikely ameliorated by antivirals-based approaches alone. First, although the new coronavirus (SARS-CoV-2) infect lung and intestine, many patients suddenly take a turn for the worse even when the viral replication appears to be under control. Second, patients with serious or critical clinical symptoms show remarked T cell lymphopenia that are more severe and more acute than human immunodeficiency virus (HIV) infection. Functional exhaustion of T cells is suggested by high expression of T-cell exhaustion markers, which again appears more acute than in HIV patients. Third, multiple cytokines are elevated among patients with severe clinical symptoms, which potentially explains the multiple organ failure associated with COVID-19. For these reasons, treatment of COVID-19 likely requires a combination of both antivirals and non-antivirals-based approaches.

CD24Fc is a biological immunomodulator in Phase II/III clinical trial stage. CD24Fc comprises the nonpolymorphic regions of CD24 attached to the Fc region of human IgG1. We have shown that CD24 is an innate checkpoint against the inflammatory response to tissue injuries or danger-associated molecular patterns (DAMPs). Preclinical and clinical studies have demonstrated that CD24Fc effectively address the major challenges associated with COVID-19. First, a Phase I clinical trial on healthy volunteers not only demonstrated safety of CD24Fc, but also demonstrated its biological activity in suppressing expression of multiple inflammatory cytokines. Second, in Phase II clinical trial in leukemia patients undergoing hematopoietic stem cell transplantation (HCT), three doses of CD24Fc effectively eliminated severe (Grade 3-4) acute graft vs host diseases (GVHD), which is caused by over reacting immune system and transplanted T cells attacking recipient target tissues. Third, in preclinical models of HIV/SIV infections, we have shown that CD24Fc ameliorated production of multiple inflammatory cytokines, reversed the loss of T lymphocytes as well as functional T cell exhaustion and reduced the leukocyte infiltration of multiple organs. It is particularly noteworthy that CD24Fc reduced the rate of pneumonia in SIV-infected Chinese rhesus monkey from 83% to 33%. Therefore, CD24Fc maybe a prime candidate for non-antiviral biological modifier for COVID-19 therapy. The phase III trial will involve 230 patients randomized into blinded placebo and CD24Fc arms, with time to clinical improvement from severe to mild symptom as the primary endpoint.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CD24Fc Treatment
Single dose at Day 1, CD24Fc, 480mg, diluted to 100ml with normal saline, IV infusion in 60 minutes.
Drug: CD24Fc
CD24Fc is given on Day 1.
Other Name: Human CD24 and human IgG Fc Fusion Protein

Placebo Comparator: Placebo
Single dose at Day 1, normal saline solution 100ml, IV infusion in 60 minutes.
Drug: Placebo
Placebo is given on Day 1.
Other Name: Saline




Primary Outcome Measures :
  1. Improvement of COVID-19 disease status [ Time Frame: 14 days ]
    Time to improve in clinical status: the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 3 or 4" to "scale 5 or higher" based on NIAID ordinal scales.


Secondary Outcome Measures :
  1. Conversion rate of clinical status at Day 8 [ Time Frame: 7 days ]
    Conversion rate of clinical status on days 8 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)

  2. Conversion rate of clinical status at Day 15 [ Time Frame: 14 days ]
    Conversion rate of clinical status on days 15 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)

  3. Hospital discharge time [ Time Frame: 14 days ]
    The discharge time or NEWS2 (National Early Warning Score 2) of ≤2 is maintained for 24 hours

  4. All cause of death [ Time Frame: 14 days ]
    All cause of death

  5. Duration of mechanical ventilation [ Time Frame: 14 days ]
    Duration of mechanical ventilation (IMV, NIV) (days)

  6. Duration of pressors [ Time Frame: 14 days ]
    Duration of pressors (days)

  7. Duration of ECMO [ Time Frame: 14 days ]
    Duration of extracorporeal membrane oxygenation (days)

  8. Duration of oxygen therapy [ Time Frame: 14 days ]
    Duration of oxygen therapy (oxygen inhalation by nasal cannula or mask) (days)

  9. Length of hospital stay [ Time Frame: 14 days ]
    Length of hospital stay (days)

  10. Absolute lymphocyte count [ Time Frame: 14 days ]
    Changes of absolute lymphocyte count in peripheral blood



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Should be at least 18 years of age,
  2. Male or female,
  3. Diagnosed with COVID-19 and confirmed SARS-coV-2 viral infection.
  4. Able to sign the consent form.
  5. Severe COVID-19 (Appendix A), or NIAID 7-point ordinal score 3 to 4 (requiring non-invasive ventilation or oxygen, a SpO2 </= 94% or tachypnea (respiratory rate >/= 24 breaths/min), Appendix B).
  6. The absolute lymphocyte count is ≤ 0.8 × 10^9 / L (8x10^5 / mL, 800 / mm3).

Exclusion Criteria:

  1. Patients with COVID 19 in critical condition or ARDS (Appendix A) or NIAID 7-point ordinal score 2 (Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)).
  2. Patients with bacterial / fungal infections.
  3. Patients who are pregnant, breastfeeding, or have a positive pregnancy test result before enrollment.
  4. Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit).
  5. Patients with known severe renal impairment (creatinine clearance ≤ 30 mL / min) or patients receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
  6. Will be transferred to a non-study site hospital within 72 hours.
  7. The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04317040


Contacts
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Contact: Pan Zheng, MD, PhD (202) 7516823 pzheng@oncoimmune.com
Contact: Martin Devenport, PhD (410) 2070582 mdevenport@oncoimmune.com

Locations
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United States, Maryland
Institute of Human Virology, University of Maryland Baltimore
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
OncoImmune, Inc.
Investigators
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Principal Investigator: Shyamasundaran Kottilil Institute of Human Virology, University of Maryland Baltimore

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Responsible Party: OncoImmune, Inc.
ClinicalTrials.gov Identifier: NCT04317040    
Other Study ID Numbers: CD24Fc-007
First Posted: March 20, 2020    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases