SPI-1005 Treatment in Severe COVID-19 Patients

• ClinicalTrials.gov Identifier: NCT04483973
• Recruitment Status: Enrolling by invitation
• First Posted: July 23, 2020
• Last Update Posted: November 8, 2022
• Sponsor: Sound Pharmaceuticals, Incorporated
• Information provided by (Responsible Party): Sound Pharmaceuticals, Incorporated

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19; Coronavirus; Coronavirus Infection; Corona Virus Infection	Drug: Ebselen; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 27, 2021
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: SPI-1005 400 mg BID; Oral administration of SPI-1005 400 mg BID for 14 days, with 30-day follow-up	Drug: Ebselen; Glutathione peroxidase mimetic; Other Name: SPI-1005
Experimental: SPI-1005 800 mg BID; Oral administration of SPI-1005 800 mg BID for 14 days, with 30-day follow-up	Drug: Ebselen; Glutathione peroxidase mimetic; Other Name: SPI-1005
Placebo Comparator: Placebo; Oral administration of matching placebo BID for 14 days, with 30-day follow-up	Drug: Placebo; Matching placebo containing excipients

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. WHO Ordinal Scale [ Time Frame: 30 days ]
   Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement. Scale is 0-8 where higher score is worse outcome.
2. Degree of supplemental oxygen [ Time Frame: 30 days ]
   Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
3. Peripheral Oxygen Saturation (SpO2) [ Time Frame: 30 days ]
   Peripheral oxygen saturation measured by pulse oximetry

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 96510

United States, Idaho

St. Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States, 83702

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63130

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

Wake Forest University

Winston-Salem, North Carolina, United States, 27109

United States, Texas

University of Texas Southwestern

Dallas, Texas, United States, 75390

Sponsors and Collaborators

Sound Pharmaceuticals, Incorporated

Investigators

• Principal Investigator: Miriam Treggiari, MD; Yale University

More Information

Publications:

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.

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.

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.

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.

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.

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. Erratum In: ACS Pharmacol Transl Sci. 2021 Apr 29;4(3):1246.

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.

• Responsible Party: Sound Pharmaceuticals, Incorporated
• ClinicalTrials.gov Identifier: NCT04483973
• Other Study ID Numbers: SPI-1005-292
• First Posted: July 23, 2020
• Last Update Posted: November 8, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sound Pharmaceuticals, Incorporated:

ebselen; SPI-1005; COVID-19; Covid; SARS-COV-2; Mpro; main protease; PLpro; papain-like protease

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Disease Attributes; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Ebselen; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Anti-Ulcer Agents; Gastrointestinal Agents; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Cyclooxygenase Inhibitors