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

NCT03891420 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: BCX4430-108272201300017C-18-0-1DMID18-0022
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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.

Conditions

COVID-19; Yellow Fever

Keywords

COVID-19; Galidesivir; Yellow Fever

Outcome Measures

Primary Outcomes (3)

• number of subjects with treatment emergent adverse events and serious adverse events

  absolute number through the end of the study, approximately 56 days

• number of subjects with change in laboratory parameters

  absolute number and change from baseline through the end of the study, approximately 56 days

• exposure of galidesivir as measured by plasma concentrations

  24 hours post dose on Day 1 through 12 hours post dose on Day 7

Secondary Outcomes (5)

• 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 in clinical status using 8-point ordinal scale in COVID-19 (Group B)

  through Day 21

• changes from baseline and time to improvement using NEWS in COVID-19 (Group B)

  through Day21

• mortality

  mortality at Day 56

Study Arms (2)

Galidesivir

EXPERIMENTAL

Galidesivir IV infusion

Drug: Galidesivir

Placebo

PLACEBO COMPARATOR

Placebo IV infusion

Drug: Placebo

Interventions

Galidesivir DRUG

Galidesivir IV infusion

Galidesivir

Placebo DRUG

Placebo IV infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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:
• 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
• 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (5)

Hospital de Clinicas da Universidade Federal do Parana

Curitiba, Paraná, Brazil

Location

Hospital Sao Vicente de Paulo-PPDS

Passo Fundo, Rio Grande do Sul, Brazil

Location

Hospital Sao Lucas da Pucrs

Porto Alegre, Rio Grande do Sul, Brazil

Location

Foundation Regional Faculty of Medicine of São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Location

Clinical Research Unit and Department of Infectious and Parasitic Diseases Hospital das Clínicas, School of Medicine, USP

São Paulo, São Paulo, 05403-010, Brazil

Location

MeSH Terms

Conditions

COVID-19; Yellow Fever

Interventions

galidesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral

Study Officials

• Esper Kallas, MD, PhD

  University of Sao Paulo, Brazil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 27, 2019
• Study Start: April 9, 2020
• Primary Completion: January 31, 2021
• Study Completion: April 30, 2021
• Last Updated: May 27, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (5)