SLV213 Treatment in Ambulatory COVID-19 Patients

A Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose Phase 2a Study of SLV213 in Ambulatory Individuals Positive for COVID-19

This Phase 2a trial recruits adult ambulatory patients who have been determined to be COVID-19 positive. The study drug SLV213 will be administered to examine its safety, tolerability and provide assessment of its effect on clinical symptoms of COVID-19. Blood samples will be taken pre-dose and at several time points post-dose for pharmacokinetic (PK) analysis.

Study Overview

• Status: Not yet recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: SLV213; Drug: SLV213; Drug: SLV213; Drug: Placebo; Drug: Placebo; Drug: Placebo

Detailed Description

This double blind, placebo-controlled study will be conducted in two parts. Part A will determine the maximum tolerated dose (MTD) that will be used in Part B to confirm tolerance and provide assessment of the effect of SLV213 on clinical symptoms of COVID-19.

Part A will consist of three sequential cohorts of 12 subjects receiving treatment administered orally either twice a day or once a day for seven consecutive days. Subjects in each cohort will be randomized to one of two treatment arms, SLV213 (8 subjects) or placebo (4 subjects). After each cohort, a Selva Safety Review Committee (SRC) will evaluate the safety of the regimen before proceeding to dose the next cohort. If a cohort is deemed to have reached an intolerable dose level, the dose prior to that level will be the MTD. PK blood samples will be collected throughout the study.

In Part B of the study 45 subjects will be dosed at the MTD (30 SLV213 and 15 Placebo) to confirm tolerance, and to provide assessment of the effect of SLV213 on clinical symptoms of COVID-19. PK blood samples will be collected throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 81
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julia Ortega; Phone Number: +1 (240) 498-0176; Email: jortega@selvarx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Agree to participate in the trial by signing the IRB approved Informed Consent
2. Age ≥ 18 years of age
3. Positive diagnosis for COVID-19 by SARS-CoV-2 PCR by nasopharyngeal swab within the past 3 days
4. Two or more COVID-19 symptoms (at least one of which must be Respiratory) rated Mild or Moderate on the COVID-19 adapted FLU-PRO Plus scale
5. SpO2 ≥ 94%
6. Ambulatory (not hospitalized) at the time of enrollment
7. Normal (or stable if abnormal per comorbidity) baseline ECG
8. Men of child-bearing potential must use birth control with heterosexual partner(s) (abstinence or condoms)

9. Women of child-bearing potential must meet all the following criteria:

   • Use of birth control (abstinence, oral contraceptives, condoms, or intrauterine device)
   • Test negative for β-subunit of HCG

Exclusion Criteria:

1. Pregnant or lactating
2. Treatment with COVID-19 antiviral such as remdesivir or SARS-CoV-2 antibodies

3. At increased risk of developing more severe COVID-19 disease (at least one of the following):

   1. Age ≥60 years
   2. Presence of pulmonary disease, specifically moderate or severe persistent asthma, chronic obstructive pulmonary disease, pulmonary hypertension, emphysema
   3. Diabetes mellitus (type 1 or 2), requiring oral medication or insulin for treatment
   4. Cardiovascular disease, including Hypertension, requiring at least 1 oral medication for treatment; congestive heart failure; coronary artery disease; cardiomyopathy; pulmonary hypertension
   5. Body mass index ≥30
   6. Chronic renal disease (but not on dialysis)
   7. Sickle cell disease or trait
4. Severe or Critical COVID-19, as indicated by respiratory distress or shortness of breath at rest; Resp Rate ≥30/min; Heart rate ≥125/min; SpO2 ≤ 93% on room air or PaO2/FiO2 ≤ 300 if on supplemental O2
5. Positive HIV or positive Hepatitis Panel
6. Treatment with any medications known to be strongly metabolized by CYP3A4 or CYP2D6

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Multiple Ascending Dose Cohort 1; Intervention: SLV213, 8 subjects will receive 200mg oral doses twice a day for seven consecutive days.	Drug: SLV213; SLV213 oral capsule (200mg) BID; Drug: SLV213; SLV213 oral capsule (400mg) BID; Drug: SLV213; SLV213 oral capsule (800mg) QD
Placebo Comparator: Placebo Comparator: Multiple Ascending Dose Cohort 1; Intervention: Placebo, 4 subjects will receive an equivalent number of oral doses twice a day for seven consecutive days.	Drug: Placebo; Placebo oral capsule (200mg) BID; Drug: Placebo; Placebo oral capsule (400mg) BID; Drug: Placebo; Placebo oral capsule (800mg) QD
Experimental: Experimental: Multiple Ascending Dose Cohort 2; Intervention: SLV213, 8 subjects will receive 400mg oral doses twice a day for seven consecutive days.	Drug: SLV213; SLV213 oral capsule (200mg) BID; Drug: SLV213; SLV213 oral capsule (400mg) BID; Drug: SLV213; SLV213 oral capsule (800mg) QD
Placebo Comparator: Placebo Comparator: Multiple Ascending Dose Cohort 2; Intervention: Placebo, 4 subjects will receive the equivalent number of oral doses twice a day for seven consecutive days.	Drug: Placebo; Placebo oral capsule (200mg) BID; Drug: Placebo; Placebo oral capsule (400mg) BID; Drug: Placebo; Placebo oral capsule (800mg) QD
Experimental: Experimental: Multiple Ascending Dose Cohort 3; Intervention: SLV213, 8 subjects will receive 800mg oral doses once a day for seven consecutive days.	Drug: SLV213; SLV213 oral capsule (200mg) BID; Drug: SLV213; SLV213 oral capsule (400mg) BID; Drug: SLV213; SLV213 oral capsule (800mg) QD
Placebo Comparator: Placebo Comparator: Multiple Ascending Dose Cohort 3; Intervention: Placebo, 4 subjects will receive the equivalent number of oral doses once a day for seven consecutive days.	Drug: Placebo; Placebo oral capsule (200mg) BID; Drug: Placebo; Placebo oral capsule (400mg) BID; Drug: Placebo; Placebo oral capsule (800mg) QD
Experimental: Experimental: Multiple Ascending Dose Cohort 4; Intervention: SLV213, 30 subjects will receive the MTD (200mg twice a day, 400mg twice a day or 800 mg once a day) oral doses for seven consecutive days.	Drug: SLV213; SLV213 oral capsule (200mg) BID; Drug: SLV213; SLV213 oral capsule (400mg) BID; Drug: SLV213; SLV213 oral capsule (800mg) QD
Placebo Comparator: Placebo Comparator: Multiple Ascending Dose Cohort 4; Intervention: Placebo, 15 subjects will receive the equivalent number of oral doses once a day or twice a day for seven consecutive days.	Drug: Placebo; Placebo oral capsule (200mg) BID; Drug: Placebo; Placebo oral capsule (400mg) BID; Drug: Placebo; Placebo oral capsule (800mg) QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events	Proportion of participants experiencing any treatment-emergent adverse events judged possibly or probably related to study drug vs. placebo (drug-related adverse events as determined by abnormal clinical laboratory tests, vitals signs, blood pressure monitoring and collection (systolic, diastolic, pulse pressure, heart rate and mean arterial pressure), physical exam and ECG parameters).	21 days following treatment end

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
COVID-19 Symptom Improvements	Time from randomization to an improvement of two points (from the status at randomization) on the COVID19 symptom scale	21 days following treatment end
COVID-19 Symptom Resolution	Time from randomization to resolution of COVID-19 clinical symptoms (e.g. fever, cough, shortness of breath, etc. as described below). Resolution defined as the start of the first 24-hour period when all symptoms are rated as mild or absent and have remained this way for 24 hours	21 days following treatment end
Negative SARC-CoV-2 Testing	Time to two successive nasopharyngeal swabs negative for SARS-CoV-2 by PCR testing	Through Day 8
SARS-CoV-2 Viral Load Change	Change in SARS-CoV-2 viral load measured in plasma samples (e.g., change in the slope of the SARS-CoV-2 log viral load assessed at baseline and Day 8)	Baseline and Day 8
SpO2/FiO2 Ratio Change	Change in SpO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) assessed at baseline then day 7	Baseline and Day 7
Oxygen Support	Number of days without oxygen by non-invasive ventilation/high flow nasal cannula or need for mechanical ventilation	21 days following treatment end
Hospitalization	Proportion of subjects requiring hospitalization	21 days following treatment end
COVID-19 Related Death	Proportion of subjects dying of COVID-19 related causes	21 days following treatment end

Collaborators and Investigators

• Sponsor: Kenneth Krantz, MD, PhD
• Collaborators: FHI Clinical, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: SLV213-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No