First-in-Human Study of Orally Administered GS-441524 for COVID-19

• ClinicalTrials.gov Identifier: NCT04859244
• Recruitment Status: Completed
• First Posted: April 26, 2021
• Last Update Posted: August 10, 2021
• Sponsor: Copycat Sciences LLC
• Information provided by (Responsible Party): Copycat Sciences LLC

Tracking Information

• First Submitted Date: April 19, 2021
• First Posted Date: April 26, 2021
• Last Update Posted Date: August 10, 2021
• Actual Study Start Date: January 1, 2021
• Actual Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2021)

Emergence of treatment-related adverse events (AEs) [ Time Frame: Day 7 ]

Treatment-related AEs are defined as significant changes to blood chemistry (CBC, CMP) or 6-lead ECG.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 21, 2021)

• Pharmacokinetic (PK) Parameter: AUC0-24h of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  AUC0-24h is defined as the concentration of drug over time between time 0 to time 24 hours.
• PK Parameter: AUClast of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  AUClast is defined as the concentration of drug from time zero to the last observable concentration.
• PK Parameter: T1/2 of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  T/2 is defined as the estimate of the terminal elimination half-life of the drug
• PK Parameter: Cmax of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  Cmax is defined as the maximum observed concentration of drug.
• PK Parameter: Tmax of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  Tmax is defined as the time (observed time point) of Cmax.
• PK Parameter: Clast of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  Clast is defined as the last observable concentration of drug.
• PK Parameter: Tlast of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  Tlast is defined as the time (observed time point) of Clast.
• PK Parameter: AUCtau of GS-441524 in Parts 1 and 2. [ Time Frame: Intensive PK: Day 1 to Day 7 ]
  AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-in-Human Study of Orally Administered GS-441524 for COVID-19
• Official Title: First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of Orally Administered GS-441524 in a Healthy Human Volunteer
• Brief Summary: This is a two-part study is to evaluate the multi-day safety, tolerability, and pharmacokinetics (PK) of orally administered GS-441524 in a healthy human volunteer.
• Detailed Description: Part 1: 750 mg GS-441524 administered once daily (QD) for 7 days. Part 2: 750 mg GS-441524 administered three times daily (TID) for 3 days.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

Drug: GS-441524

750 mg administered as a solution

Other Name: Parent nucleoside of remdesivir

Study Arms

• Experimental: Part 1: GS-441524 (QD, 7 days)
  750 mg GS-441524 administered QD for 7 days
  Intervention: Drug: GS-441524
• Experimental: Part 2: GS-441524 (TID, 3 days)
  750 mg GS-441524 administered TID for 3 days
  Intervention: Drug: GS-441524

Publications *

• Humeniuk R, Mathias A, Cao H, Osinusi A, Shen G, Chng E, Ling J, Vu A, German P. Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects. Clin Transl Sci. 2020 Sep;13(5):896-906. doi: 10.1111/cts.12840. Epub 2020 Aug 5.
• Tempestilli M, Caputi P, Avataneo V, Notari S, Forini O, Scorzolini L, Marchioni L, Ascoli Bartoli T, Castilletti C, Lalle E, Capobianchi MR, Nicastri E, D'Avolio A, Ippolito G, Agrati C; COVID 19 INMI Study Group. Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19. J Antimicrob Chemother. 2020 Oct 1;75(10):2977-2980. doi: 10.1093/jac/dkaa239.
• Davis MR, Pham CU, Cies JJ. Remdesivir and GS-441524 plasma concentrations in patients with end-stage renal disease on haemodialysis. J Antimicrob Chemother. 2021 Feb 11;76(3):822-825. doi: 10.1093/jac/dkaa472. No abstract available.
• Yan VC, Muller FL. Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment. ACS Med Chem Lett. 2020 Jun 23;11(7):1361-1366. doi: 10.1021/acsmedchemlett.0c00316. eCollection 2020 Jul 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2021): 1
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 1, 2021
• Actual Primary Completion Date: May 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Willing and able to provide written informed consent
• Negative pregnancy test at screening and prior to dosing
• Minimum body weight of 50 kg and body mass index (BMI) of 18-32 kg/m2

Exclusion Criteria:

• Use of other investigational drugs within 28 days of dosing
• Positive pregnancy test
• Abuse of alcohol or drugs
• Other clinically significant medical conditions or laboratory abnormalities

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04859244
• Other Study ID Numbers: CC-2021-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All collected IPD
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Within 6 months after publication
• Access Criteria: Materials available upon request

• Current Responsible Party: Copycat Sciences LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Copycat Sciences LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Victoria Yan; Copycat Sciences

• PRS Account: Copycat Sciences LLC
• Verification Date: April 2021