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

Tracking Information

• First Submitted Date: July 13, 2020
• First Posted Date: July 23, 2020
• Last Update Posted Date: November 8, 2022
• Actual Study Start Date: August 27, 2021
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 21, 2020): Number of participants with treatment-related adverse events [ Time Frame: 30 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 6, 2020)

• 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.
• Degree of supplemental oxygen [ Time Frame: 30 days ]
  Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
• Peripheral Oxygen Saturation (SpO2) [ Time Frame: 30 days ]
  Peripheral oxygen saturation measured by pulse oximetry

Original Secondary Outcome Measures (submitted: July 21, 2020)

• WHO Ordinal Scale [ Time Frame: 30 days ]
  Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement
• Degree of supplemental oxygen [ Time Frame: 30 days ]
  Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
• Peripheral Oxygen Saturation (SpO2) [ Time Frame: 30 days ]
  Peripheral oxygen saturation measured by pulse oximetry

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

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Covid19
• Coronavirus
• Coronavirus Infection
• Corona Virus Infection

Intervention

• Drug: Ebselen
  Glutathione peroxidase mimetic
  Other Name: SPI-1005
• Drug: Placebo
  Matching placebo containing excipients

Study Arms

• Experimental: SPI-1005 400 mg BID
  Oral administration of SPI-1005 400 mg BID for 14 days, with 30-day follow-up
  Intervention: Drug: Ebselen
• Experimental: SPI-1005 800 mg BID
  Oral administration of SPI-1005 800 mg BID for 14 days, with 30-day follow-up
  Intervention: Drug: Ebselen
• Placebo Comparator: Placebo
  Oral administration of matching placebo BID for 14 days, with 30-day follow-up
  Intervention: Drug: Placebo

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.

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: July 21, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (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: NCT04483973
• Other Study ID Numbers: SPI-1005-292
• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sound Pharmaceuticals, Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Sound Pharmaceuticals, Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Miriam Treggiari, MD; Yale University

• PRS Account: Sound Pharmaceuticals, Incorporated
• Verification Date: November 2022