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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03891420
Recruitment Status : Recruiting
First Posted : March 27, 2019
Last Update Posted : July 23, 2020
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
COVID-19 Yellow Fever Drug: Galidesivir Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 9, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

Arm Intervention/treatment
Experimental: Galidesivir
Galidesivir IV infusion
Drug: Galidesivir
Galidesivir IV infusion

Placebo Comparator: Placebo
Placebo IV infusion
Drug: Placebo
Placebo IV infusion




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]

Secondary Outcome Measures :
  1. yellow fever virus (YFV) titer (Group A) [ Time Frame: change in YFV titer from baseline through Day 21 ]
  2. antiviral effect on SARS-CoV-2 in the respiratory tract - COVID-19 (Group B) [ Time Frame: change in SARS-CoV-2 from baseline through Day 21 ]
  3. changes in clinical status using 8-point ordinal scale in COVID-19 (Group B) [ Time Frame: through Day 21 ]
  4. changes from baseline and time to improvement using NEWS in COVID-19 (Group B) [ Time Frame: through Day21 ]
  5. mortality [ Time Frame: mortality at Day 56 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03891420


Contacts
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Contact: Study Director 919-859-1302 clinicaltrials@biocryst.com

Locations
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Brazil
Hospital de Clinicas da Universidade Federal do Parana Recruiting
Curitiba, Parana, Brazil
Hospital Sao Vicente de Paulo-PPDS Recruiting
Passo Fundo, Rio Grande Do Sul, Brazil
Hospital Sao Lucas da Pucrs Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil
Foundation Regional Faculty of Medicine of São José do Rio Preto Not yet recruiting
São José Do Rio Preto, SP, Brazil
Clinical Research Unit and Department of Infectious and Parasitic Diseases Hospital das Clínicas, School of Medicine, USP Recruiting
São Paulo, SP, Brazil, 05403-010
Sponsors and Collaborators
BioCryst Pharmaceuticals
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Esper Kallas, MD, PhD University of Sao Paulo, Brazil
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Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03891420    
Other Study ID Numbers: BCX4430-108
272201300017C-18-0-1 ( U.S. NIH Grant/Contract )
DMID18-0022 ( Other Identifier: NIAID )
First Posted: March 27, 2019    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioCryst Pharmaceuticals:
COVID-19
Galidesivir
Yellow Fever
Additional relevant MeSH terms:
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Yellow Fever
Fever
Body Temperature Changes
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral