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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

Tracking Information
First Submitted Date  ICMJE March 15, 2019
First Posted Date  ICMJE March 27, 2019
Last Update Posted Date July 23, 2020
Actual Study Start Date  ICMJE April 9, 2020
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
  • yellow fever virus (YFV) titer (Group A) [ Time Frame: change in YFV titer from baseline through Day 21 ]
  • 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 ]
  • changes in clinical status using 8-point ordinal scale in COVID-19 (Group B) [ Time Frame: through Day 21 ]
  • changes from baseline and time to improvement using NEWS in COVID-19 (Group B) [ Time Frame: through Day21 ]
  • mortality [ Time Frame: mortality at Day 56 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • yellow fever virus (YFV) titer [ Time Frame: change in YFV titer from baseline through Day 21 ]
  • mortality [ Time Frame: mortality at Day 56 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effects of Galidesivir in Yellow Fever or COVID-19
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • COVID-19
  • Yellow Fever
Intervention  ICMJE
  • Drug: Galidesivir
    Galidesivir IV infusion
  • Drug: Placebo
    Placebo IV infusion
Study Arms  ICMJE
  • Experimental: Galidesivir
    Galidesivir IV infusion
    Intervention: Drug: Galidesivir
  • Placebo Comparator: Placebo
    Placebo IV infusion
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2020)
132
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2019)
54
Estimated Study Completion Date  ICMJE May 31, 2021
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Director 919-859-1302 clinicaltrials@biocryst.com
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03891420
Other Study ID Numbers  ICMJE BCX4430-108
272201300017C-18-0-1 ( U.S. NIH Grant/Contract )
DMID18-0022 ( Other Identifier: NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BioCryst Pharmaceuticals
Study Sponsor  ICMJE BioCryst Pharmaceuticals
Collaborators  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE
Principal Investigator: Esper Kallas, MD, PhD University of Sao Paulo, Brazil
PRS Account BioCryst Pharmaceuticals
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP