Clinical trial NCT04483973: SPI-1005 Treatment in Severe COVID-19 Patients
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Severe COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Covid19
Coronavirus
Coronavirus Infection
Corona Virus Infection
Keywords: ebselen
SPI-1005
COVID-19
Covid
SARS-COV-2
Mpro
main protease
PLpro
papain-like protease
Lead sponsor: Sound Pharmaceuticals, Incorporated
Sponsor class: INDUSTRY
First posted: 2020-07-23
Enrollment: 60
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: The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.


Eligibility criteria: Inclusion Criteria:

* Adults ≥18 years of age
* Positive nCoV2 PCR test by nasopharyngeal, oral, saliva, or respiratory sample
* Clinical signs, symptoms, and respiratory status consistent with severe COVID-19
* Score of 5-7 on the WHO Ordinal Scale
* Onset of severe COVID-19 symptoms ≤7 days of study enrollment
* Subject is in-patient at time of randomization to study treatment
* Subject or legally authorized representative is willing and able to provide informed consent, and agrees for subject to comply with planned study procedures including reproductive requirements

Exclusion Criteria:

* Female patients who are pregnant or breastfeeding.
* Participation in another interventional investigational drug or device study concurrently or within 30 days prior to study consent.
* Patients with impaired hepatic or renal function.
* Subject has any other illness or condition that, in the opinion of the investigator, would prohibit the subject from participating.

Primary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: 30 days
Secondary outcomes:
measure: WHO Ordinal Scale
timeFrame: 30 days
measure: Degree of supplemental oxygen
timeFrame: 30 days
measure: Peripheral Oxygen Saturation (SpO2)
timeFrame: 30 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boise
country: United States
facility: St. Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: Yale University
name: Miriam Treggiari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9.
citation: Menendez CA, Bylehn F, Perez-Lemus GR, Alvarado W, de Pablo JJ. Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease. Sci Adv. 2020 Sep 11;6(37):eabd0345. doi: 10.1126/sciadv.abd0345. Print 2020 Sep.
citation: Weglarz-Tomczak E, Tomczak JM, Talma M, Burda-Grabowska M, Giurg M, Brul S. Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2. Sci Rep. 2021 Feb 11;11(1):3640. doi: 10.1038/s41598-021-83229-6.
citation: Brown AS, Ackerley DF, Calcott MJ. High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor. Molecules. 2020 Oct 13;25(20):4666. doi: 10.3390/molecules25204666.
citation: Haritha CV, Sharun K, Jose B. Ebselen, a new candidate therapeutic against SARS-CoV-2. Int J Surg. 2020 Dec;84:53-56. doi: 10.1016/j.ijsu.2020.10.018. Epub 2020 Oct 23. No abstract available.
citation: Chen T, Fei CY, Chen YP, Sargsyan K, Chang CP, Yuan HS, Lim C. Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir. ACS Pharmacol Transl Sci. 2021 Mar 26;4(2):898-907. doi: 10.1021/acsptsci.1c00022. eCollection 2021 Apr 9.
citation: Sies H, Parnham MJ. Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections. Free Radic Biol Med. 2020 Aug 20;156:107-112. doi: 10.1016/j.freeradbiomed.2020.06.032. Epub 2020 Jun 26.