A Phase 1b Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Pharmacokinetics, and Anti-viral Effects of Galidesivir Administered Via Intravenous Infusion to Subjects With Yellow Fever or COVID-19
Overview
- Phase
- Phase 1
- Intervention
- Galidesivir
- Conditions
- COVID-19
- Sponsor
- BioCryst Pharmaceuticals
- Enrollment
- 24
- Locations
- 5
- Primary Endpoint
- exposure of galidesivir as measured by plasma concentrations
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.
Detailed Description
This is a randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetics (PK), safety, and antiviral effects of galidesivir administered via intravenous (IV) infusion vs. placebo in hospitalized adult subjects with either Yellow Fever (Group A) or COVID-19 (Group B). The study will be conducted in two parts, and each Group (A or B) will proceed independently through the study. Part 1 is a dose ranging study with three sequential cohorts of eight patients each that will be randomized 3:1 to receive IV galidesivir or placebo every 12 hours for 7 days. Upon completion of part 1, an optimized dosing regimen of galidesivir will be selected for part 2, based on part 1 results including safety, PK, viral load reduction, and improvement in signs and symptoms and clinical manifestations, and mortality. In part 2, up to 42 patients will be randomized 2:1 to receive IV galidesivir or placebo. After treatment, the patients will remain hospitalized until resolution of symptoms allows release. All patients will be followed for mortality through Day 56.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Group A - Yellow Fever
- •Ability to provide written informed consent
- •Males and nonpregnant, non-breast-feeding females, aged 18 years or older
- •Subject weight ≥ 50 kg (110 lb.)
- •Positive test for YFV by molecular amplification of the virus in the blood
- •First onset of symptoms of YF occurring within the previous 7 days
- •Male and female subjects must agree to the contraception requirements and must meet the inclusion criteria regarding contraception as outlined in the protocol
- •CLCR of at least 60 mL/min by Cockcroft-Gault equation
- •AST \< 5000 u/L
- •Indirect bilirubin \< 1.5 mg/dL
Exclusion Criteria
- •Group A - Yellow Fever
- •Any clinically significant medical condition or medical history that, in the opinion of the investigator or sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participation for that subject
- •Employment by the study site, or an immediate family relationship to either study site employees or Sponsor employee
- •Lack of suitable veins for venipuncture/cannulation as assessed by the Investigator at Screening
- •Participation in any other investigational drug or vaccine study currently or within the past 30 days
- •Diagnosis of YF vaccine-related viscerotropic disease
- •Subjects with hepatic encephalopathy as defined by Conn Score ≥
- •Subject has severe immunosuppression or immunodeficiency, leukemia, lymphoma, thymic disease, generalized malignancy, or radiation therapy (within the past 3 months), or is undergoing current treatment with immunosuppressive drugs, defined as drugs that impair immune responses to infections
- •A treatment plan for YF that would include concomitant administration of antiviral medications
- •Inclusion Criteria Group B - COVID-19
Arms & Interventions
Galidesivir
Galidesivir IV infusion
Intervention: Galidesivir
Placebo
Placebo IV infusion
Intervention: Placebo
Outcomes
Primary Outcomes
exposure of galidesivir as measured by plasma concentrations
Time Frame: 24 hours post dose on Day 1 through 12 hours post dose on Day 7
number of subjects with change in laboratory parameters
Time Frame: absolute number and change from baseline through the end of the study, approximately 56 days
number of subjects with treatment emergent adverse events and serious adverse events
Time Frame: absolute number through the end of the study, approximately 56 days
Secondary Outcomes
- yellow fever virus (YFV) titer (Group A)(change in YFV titer from baseline through Day 21)
- antiviral effect on SARS-CoV-2 in the respiratory tract - COVID-19 (Group B)(change in SARS-CoV-2 from baseline through Day 21)
- changes from baseline and time to improvement using NEWS in COVID-19 (Group B)(through Day21)
- changes in clinical status using 8-point ordinal scale in COVID-19 (Group B)(through Day 21)
- mortality(mortality at Day 56)