A Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effects of Galidesivir in Yellow Fever or COVID-19

BioCryst

Status and phase

Terminated

Phase 1

Conditions

COVID-19

Yellow Fever

Treatments

Drug: Galidesivir

Drug: Placebo

Study type

Interventional

Funder types

Industry

NIH

Identifiers

NCT03891420

272201300017C-18-0-1 (U.S. NIH Grant/Contract)

DMID18-0022 (Other Identifier)

BCX4430-108

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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
Neutrophil count < 7500 /mm3
International Normalized Ratio (INR) < 1.5

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 ≥ 1.
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

Ability to provide written informed consent, accept randomization to any assigned treatment arm, and comply with planned study procedures
Males and nonpregnant, non-breast-feeding females, aged 18 years or older
Male and female subjects must agree to the contraception requirements and must meet the inclusion criteria regarding contraception as outlined in the protocol
Subject weight ≥ 50 kg (110 lb.)
Clinical syndrome consistent with moderate-severe (but not critically ill) COVID-19, defined by at least one of the following:
1. Symptoms of acute viral lower respiratory tract infection, such as fever, non-productive cough, dyspnea, and either 1) a pulse oximetry oxygen saturation (SpO2) ≤ 94% or a respiratory rate > 24 breaths/minute as measured at rest without use of supplemental oxygen or 2) a clinical requirement for supplemental oxygen treatment or non-invasive mechanical ventilation
2. Radiographic pulmonary findings seen on chest imaging (chest X-ray or computed tomography [CT scan]) consistent with COVID-19
Positive test for SARS-CoV-2 by molecular amplification of the virus in a respiratory specimen (nasopharyngeal, oropharyngeal, lower respiratory tract [eg, expectorated sputum]) collected < 96 hours prior to randomization. Note: subjects may have a positive test recorded prior to screening if they are admitted to the hospital with a presumed case of COVID-19

Exclusion Criteria: Group B - COVID-19

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 the subject
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
A clinical treatment plan that would include concomitant administration of any other experimental treatment or off-label use of marketed medications that are intended as specific treatment for the COVID-19 clinical syndrome or the SARS-CoV-2 infection. Any such medications must be discontinued prior to study enrollment, unless a formal written standard of care policy document from the national, state, or institutional authorities requires otherwise.
Severe or rapidly progressive disease or medical condition of any type such that death is an expected or likely outcome within 72 hours or that would require referral or transfer to another medical facility
Severe renal impairment (estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73m2) or receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis
Severe liver disease by medical history or ALT or AST > 5 times upper limit of normal
Congestive heart failure by medical history ≥ Class 3
Requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization