Clinical trial NCT04317040: Efprezimod Alfa (CD24Fc, MK-7110) as a Non-antiviral Immunomodulator in COVID-19 Treatment (MK-7110-007)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronavirus Disease 2019 (COVID-19)
Lead sponsor: Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2020-03-20
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the efficacy and safety of efprezimod alfa in hospitalized adult participants who are diagnosed with coronavirus disease 2019 (COVID-19) and receiving oxygen support.

The primary hypothesis of the study is clinical improvement in the experimental group versus the control group.


Eligibility criteria: Inclusion Criteria:

* Diagnosed with coronavirus disease 2019 (COVID-19) and confirmed severe acute respiratory syndrome coronavirus 2 (SARS-coV-2) viral infection
* Severe or critical COVID-19, or National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal score 2, 3 or 4 (Scale 2: requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Scale 3: non-invasive ventilation or high flow oxygen devices; Scale 4: supplemental oxygen support; a peripheral capillary oxygen saturation (SpO2) \</= 94% or tachypnea (respiratory rate \>/= 24 breaths/min). Intubation should be within 7 days

Exclusion Criteria:

* Participants who are pregnant, breastfeeding, or have a positive pregnancy test result before enrollment
* Participants previously enrolled in the efprezimod alfa study
* Intubation for invasive mechanical ventilation is over 7 days
* Documented acute renal or hepatic failure
* The investigator believes that participating in the trial is not in the best interests of the participant, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues)

Primary outcomes:
measure: Time to Improvement in Coronavirus Disease 2019 (COVID-19) Clinical Status
timeFrame: Up to Day 29
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to 30 days
Secondary outcomes:
measure: Percentage of Participants Who Died or Had Respiratory Failure (RF)
timeFrame: Up to Day 29
measure: Time to Disease Progression in Clinical Status of COVID-19
timeFrame: Up to Day 29
measure: Number of Participants Who Died Due to Any Cause
timeFrame: Up to Day 29
measure: Rate of Clinical Relapse
timeFrame: Up to Day 29
measure: Conversion Rate of COVID-19 Clinical Status
timeFrame: Up to Day 15
measure: Time to Hospital Discharge
timeFrame: Up to Day 29
measure: Duration of MV
timeFrame: Up to Day 29
measure: Duration of Pressors
timeFrame: Up to Day 29
measure: Duration of ECMO
timeFrame: Up to Day 29
measure: Duration of High Flow Oxygen Therapy
timeFrame: Up to Day 29
measure: Length of Hospital Stay
timeFrame: Up to 90 days
measure: Change From Baseline in Absolute Lymphocyte Count
timeFrame: Baseline and up to Day 15
measure: Change From Baseline in D-Dimer Concentration
timeFrame: Baseline and up to Day 15
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Baptist Health Research Institute
state: Florida
city: Annapolis
country: United States
facility: Anne Anundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Institute of Human Virology, University of Maryland Baltimore
state: Maryland
city: Rockville
country: United States
facility: Shady Grove Medical Center
state: Maryland
city: Silver Spring
country: United States
facility: White Oak Medical Center
state: Maryland
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Houston
country: United States
facility: University of Texas at Houston
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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citation: Chen GY, Chen X, King S, Cavassani KA, Cheng J, Zheng X, Cao H, Yu H, Qu J, Fang D, Wu W, Bai XF, Liu JQ, Woodiga SA, Chen C, Sun L, Hogaboam CM, Kunkel SL, Zheng P, Liu Y. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat Biotechnol. 2011 May;29(5):428-35. doi: 10.1038/nbt.1846. Epub 2011 Apr 10.
citation: Chen GY, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5.
citation: Tian RR, Zhang MX, Zhang LT, Zhang P, Ma JP, Liu M, Devenport M, Zheng P, Zhang XL, Lian XD, Ye M, Zheng HY, Pang W, Zhang GH, Zhang LG, Liu Y, Zheng YT. CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS. Antiviral Res. 2018 Sep;157:9-17. doi: 10.1016/j.antiviral.2018.07.004. Epub 2018 Jul 3.
citation: Tian RR, Zhang MX, Liu M, Fang X, Li D, Zhang L, Zheng P, Zheng YT, Liu Y. CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys. Cell Mol Immunol. 2020 Aug;17(8):887-888. doi: 10.1038/s41423-020-0452-5. Epub 2020 May 7. No abstract available.
citation: Welker J, Pulido JD, Catanzaro AT, Malvestutto CD, Li Z, Cohen JB, Whitman ED, Byrne D, Giddings OK, Lake JE, Chua JV, Li E, Chen J, Zhou X, He K, Gates D, Kaur A, Chen J, Chou HY, Devenport M, Touomou R, Kottilil S, Liu Y, Zheng P; SAC-COVID Study Team. Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Infect Dis. 2022 May;22(5):611-621. doi: 10.1016/S1473-3099(22)00058-5. Epub 2022 Mar 11.
citation: Song NJ, Allen C, Vilgelm AE, Riesenberg BP, Weller KP, Reynolds K, Chakravarthy KB, Kumar A, Khatiwada A, Sun Z, Ma A, Chang Y, Yusuf M, Li A, Zeng C, Evans JP, Bucci D, Gunasena M, Xu M, Liyanage NPM, Bolyard C, Velegraki M, Liu SL, Ma Q, Devenport M, Liu Y, Zheng P, Malvestutto CD, Chung D, Li Z. Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. J Hematol Oncol. 2022 Jan 10;15(1):5. doi: 10.1186/s13045-021-01222-y.