Clinical trial NCT04843787: SLV213 Treatment in Ambulatory COVID-19 Patients
Official title: A Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose Phase 2a Study of SLV213 in Ambulatory Individuals Positive for COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Lead sponsor: Selva Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: FHI Clinical, Inc.
First posted: 2021-04-14
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multiple Ascending Dose (MAD)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-Emergent Adverse Events
timeFrame: 21 days following treatment end
Secondary outcomes:
measure: COVID-19 Symptom Improvements
timeFrame: 21 days following treatment end
measure: COVID-19 Symptom Resolution
timeFrame: 21 days following treatment end
measure: Negative SARC-CoV-2 Testing
timeFrame: Through Day 8
measure: SARS-CoV-2 Viral Load Change
timeFrame: Baseline and Day 8
measure: SpO2/FiO2 Ratio Change
timeFrame: Baseline and Day 7
measure: Oxygen Support
timeFrame: 21 days following treatment end
measure: Hospitalization
timeFrame: 21 days following treatment end
measure: COVID-19 Related Death
timeFrame: 21 days following treatment end
Other outcomes:
Locations:
Study officials:
References: