Hospitalized influenza MedDRA version: 19.0 Level: PT Classification code 10022000 Term: Influenza System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Danirixin
Product Code: GSK1325756
Pharmaceutical Form: Powder for injection
INN or Proposed INN: GSK1325756H
CAS Number: N/A
Current Sponsor code: GSK1325756
Other descriptive name: Da
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: AGE 1. Adults 18 years (as per local laws) of age and older at the time of signing the informed consent. TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 2. Presence of fever (=38.0 °C [=100.4 °F] by any route) at Baseline (enrollment) or history of fever/feverishness during the 48 hours prior. 3. O2 saturation 24 breaths per minute. For those subjects who require ventilator support or oxygen supplementation, this requirement is waived. - Heart rate >100 bpm - Systolic bp 30mL/min. 9. Baseline Liver Function Tests as follows: (refer to the protocol P31 For further details) SEX 10. Male or Female subjects could be eligible if : Males: Male subjects with female partners of child bearing potential must comply with the until at least 36 hours (five half-lives) after the last dose of study medication. a. Vasectomy with documentation of azoospermia. b. Male condom plus partne
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL) 1. Subjects who, in the opinion of the investigator, are not likely to survive the next 48 hours beyond Baseline; 2. Immunosuppression, whether due to primary immunosuppressive conditions, such as history of inherited immunodeficiency syndromes, HIV infection, or secondary conditions, such as immunosuppressive medication, stem cell or solid organ transplantation, or malignancy; 3. Documented current liver disease (including Hepatitis A, B, or C), or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones); 4. QTc Criteria: QTcB or QTcF >480 msec or >500 msec with bundle branch block; 5. For subjects enrolled in the sentinel cohorts: diabetes mellitus and chronic kidney disease; 6. Subjects who require dialysis, or are on renal replacement therapies; 7. Subjects who require extra corporeal membrane oxygenation (ECMO) at baseline (enrolled subjects who subsequently require ECMO may continue in the study) 8. Women who are pregnant as determined by a positive human chorionic gonadotrophin (hCG) ultrasensitive test prior to dosing or women who are breastfeeding; CONCOMITANT MEDICATIONS 9. Subjects who received other treatments for influenza including vitaglutam, umifenovir, and neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) for more than 72 hours during current acute illness; 10. Subjects who received any immunoglobulins within 6 months of screening or planned administration of any of these products during the treatment period. 11. Subjects treated with cytotoxic or immunosuppressive drugs within six months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed. RELEVANT HABITS 12. Known history of drug abuse within 6 months of study start. CONTRAINDICATIONS 13. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA 14. Absolute neutrophil count <1.0 Gi/L 15. Subjects who have participated in a clinical trial using an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the efficacy of treatment with IV DNX twice daily given with oral oseltamivir compared to oral oseltamivir twice daily on time to clinical response (TTCR);Secondary Objective: - To assess the efficacy of treatment with IV DNX twice daily given with oral oseltamivir compared to oral oseltamivir twice daily on time to respiratory response (TTRR) - To evaluate clinical measures of influenza illness following treatment with IV DNX twice daily given with oral oseltamivir compared to oral oseltamivir twice daily - To characterize the safety and tolerability of IV DNX twice daily given with oral oseltamivir compared to oral oseltamivir twice daily - To characterize the pharmacokinetics of IV DNX in subjects hospitalized for influenza;Primary end point(s): Primary endpoint: Time to Clinical Response (composite) • Hospital discharge OR • Normalization of: o Temperature; and o Oxygen saturation; and o Respiratory status/Heart Rate/SBP (normalization of 2 out of these 3 parameters) ;Timepoint(s) of evaluation of this end point: Days 1 through 45 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to Respiratory Response defined as meeting at least one criterion below - Return to pre-morbid oxygen requirement (subjects with chronic oxygen use), OR - Return to no requirement of supplemental oxygen, OR - Respiratory rate =24/min (without supplemental oxygen) • Time to absence of fever • Time to improved oxygen saturation • Time to improved heart rate • Time to improved SBP • Proportion of subjects with clinical response over time • Proportion of subjects with improved respiratory status over time • Time to improvement of ventilation status: modality, frequencies and durations of invasive and non-invasive ventilator support, duration of oxygen supplementation. • Length of stay in the ICU • Frequency of ICU admission and readmission • Length of stay in the hospital • Rates of development of septic shock • Frequency of antibiotic use • Proportion of subjects with improvement in Ordinal scale of clinical efficacy over time : - Death - Mechanical vent - In the ICU - Non-ICU hospitalization - Hospital discharge • Frequency of adverse events (AEs) and serious adverse events (SAEs) • Frequency of adverse events of special interest (AESIs) • Change from baseline in clinical laboratory evaluations, and ECG parameters • Standard pharmacokinetic parameters for IV danirixin (i.e. AUC, Cmax, Cavg). ;Timepoint(s) of evaluation of this end point: Day 1 through 45 | — |
Countries
Korea, Republic of, Mexico, Netherlands, Russian Federation, Spain, Sweden, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed