A Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose Phase 2a Study of SLV213 in Ambulatory Individuals Positive for COVID-19
Overview
- Phase
- Phase 2
- Intervention
- SLV213
- Conditions
- Covid19
- Sponsor
- Kenneth Krantz, MD, PhD
- Enrollment
- 81
- Primary Endpoint
- Treatment-Emergent Adverse Events
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
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.
Investigators
Kenneth Krantz, MD, PhD
Chief Medical Officer
Selva Therapeutics, Inc.
Eligibility Criteria
Inclusion Criteria
- •Agree to participate in the trial by signing the IRB approved Informed Consent
- •Age ≥ 18 years of age
- •Positive diagnosis for COVID-19 by SARS-CoV-2 PCR by nasopharyngeal swab within the past 3 days
- •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
- •Ambulatory (not hospitalized) at the time of enrollment
- •Normal (or stable if abnormal per comorbidity) baseline ECG
- •Men of child-bearing potential must use birth control with heterosexual partner(s) (abstinence or condoms)
- •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
- •Pregnant or lactating
- •Treatment with COVID-19 antiviral such as remdesivir or SARS-CoV-2 antibodies
- •At increased risk of developing more severe COVID-19 disease (at least one of the following):
- •Age ≥60 years
- •Presence of pulmonary disease, specifically moderate or severe persistent asthma, chronic obstructive pulmonary disease, pulmonary hypertension, emphysema
- •Diabetes mellitus (type 1 or 2), requiring oral medication or insulin for treatment
- •Cardiovascular disease, including Hypertension, requiring at least 1 oral medication for treatment; congestive heart failure; coronary artery disease; cardiomyopathy; pulmonary hypertension
- •Body mass index ≥30
- •Chronic renal disease (but not on dialysis)
- •Sickle cell disease or trait
Arms & Interventions
Experimental: Multiple Ascending Dose Cohort 3
Intervention: SLV213, 8 subjects will receive 800mg oral doses once a day for seven consecutive days.
Intervention: SLV213
Experimental: Multiple Ascending Dose Cohort 1
Intervention: SLV213, 8 subjects will receive 200mg oral doses twice a day for seven consecutive days.
Intervention: SLV213
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.
Intervention: Placebo
Experimental: Multiple Ascending Dose Cohort 2
Intervention: SLV213, 8 subjects will receive 400mg oral doses twice a day for seven consecutive days.
Intervention: SLV213
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.
Intervention: Placebo
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.
Intervention: Placebo
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.
Intervention: SLV213
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Treatment-Emergent Adverse Events
Time Frame: 21 days following treatment end
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).
Secondary Outcomes
- COVID-19 Symptom Improvements(21 days following treatment end)
- COVID-19 Related Death(21 days following treatment end)
- COVID-19 Symptom Resolution(21 days following treatment end)
- SpO2/FiO2 Ratio Change(Baseline and Day 7)
- Hospitalization(21 days following treatment end)
- SARS-CoV-2 Viral Load Change(Baseline and Day 8)
- Oxygen Support(21 days following treatment end)
- Negative SARC-CoV-2 Testing(Through Day 8)