Lung Injury, AcutePhase 2NCT01597635

The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury

A Phase 2 study testing Dose 1 GSK2586881, Dose 2 GSK2586881 and Dose 3 GSK2586881 in people with Lung Injury, Acute, run by GlaxoSmithKline at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an early phase (phase IIa), randomized, multi-center study in subjects with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The purpose of this study is to investigate the safety of GSK2586881 and to determine what effects it has on people with Acute Lung Injury (ALI) or Acute… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Lung Injury, Acute
What is being tested?: Dose 1 GSK2586881, Dose 2 GSK2586881 and Dose 3 GSK2586881
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 19 sitesin 2 countries
Study dates: 1 Sep 2012to 6 Oct 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, 18 - 80 years of age (inclusive)
Diagnosis of ALI with acute onset of PaO2/FiO2 ratio less than or equal to 300, and bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric, and requirement for positive pressure ventilation via an endotracheal tube, and no clinical evidence of left atrial hypertension
Cause of ALI thought to be associated with infection, sepsis, pneumonia, aspiration, or similar as judged by the PI and/or medical monitor
The subject must be randomized into the study within 48 hours from the time of diagnosis of ALI
Period of hemodynamic stability (e.g. 4-6 hours) prior to the initiation of study treatment not requiring resuscitative measures with stable pressor requirements. In this study low-dose arginine vasopressin is not considered a pressor, and is permitted in Parts A and B.
If mechanically ventilated, duration of mechanical ventilation must be less than 72 hours before dosing begins

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BMI within the range 19.0 - 38.0 kg/m2 inclusive
The subject or legal decision maker is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
QTcB or QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
Alanine aminotransferase (ALT) less than 5 x Upper Limit of Normal (ULN); bilirubin less than or equal to 1.5 x ULN.

Who cannot join

Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.
Known positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody
Current or chronic history of liver disease (Child Pugh score of greater than or equal to 10), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Known history of substance abuse or alcohol abuse, within 6 months of the study causing chronic liver disease such as cirrhosis, chronic ascites or portal hypertension, or known evidence of withdrawal syndrome within the past 6 months.
The subject has participated in a clinical trial and has received 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).
Inability to discontinue use of Angiotensin converting enzyme type 1 inhibitors or Angiotensin receptor blockers.

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Patients requiring high doses of loop diuretics with significant intravascular volume depletion, as assessed clinically
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 GSK Medical Monitor, contraindicates their participation
Pregnant females as determined by positive serum or urine hCG test prior to dosing
Lactating females
Unwillingness or inability to follow the procedures outlined in the protocol
Subject is legally incapacitated (e.g. a prisoner)
History of sensitivity to heparin or heparin-induced thrombocytopenia
Unstable Hemoglobin (Hb less than 7) at time of drug infusion
Malignancy or other irreversible condition for which 6 month mortality is estimated to be greater than 50%
Arterial blood pH less than 7.1 or serum HCO3 - less than 15 (if ABG not available) before infusion is started
Known severe chronic respiratory disease:
known Forced Expiratory Volume in 1 second (FEV1)/ Forced Vital Capacity (FVC) less than 45% predicted, or
known chronic hypercapnia (PaCO2 greater than 45 mmHg) or chronic hypoxemia (PaO2 less than 55 mmHg) on FiO2 =0.21, or
known FEV1 less than 15 ml/kg (e.g. 1L for 70 kg person), or
known radiographic evidence of chronic interstitial infiltration, or
known hospitalization within the past six months for respiratory failure (PaCO2 greater than 50 mmHg or PaO2 less than 55 mmHg, or oxygen saturation less than 88% on FiO2 = 0.21), or
known chronic restrictive, obstructive, neuromuscular, chest wall, or pulmonary vascular disease resulting in severe exercise restriction
Known history of neuromuscular disease that would affect time on mechanical ventilation or impairs ability to ventilate spontaneously
Vasculitis with diffuse alveolar hemorrhage
Lung transplantation
Pre-existing renal failure on hemodialysis or peritoneal dialysis requiring renal replacement therapy
A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.

Trial locations and contacts

19 sites in 2 countries.

Country

City, postcode or hospital

19 sites in 2 countries

United States13 sites

GSK Investigational Site
Ann Arbor, Michigan, 48109
GSK Investigational Site
Charleston, South Carolina, 29425
GSK Investigational Site
Chicago, Illinois, 60611
GSK Investigational Site
Columbus, Ohio, 43215
GSK Investigational Site
Durham, North Carolina, 27710
GSK Investigational Site
Greensboro, North Carolina, 27403
GSK Investigational Site
New York, New York, 10003
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
Philadelphia, Pennsylvania, 19107
GSK Investigational Site
Portland, Oregon, 97239
GSK Investigational Site
Sacramento, California, 95817
GSK Investigational Site
Springfield, Massachusetts, 01199
GSK Investigational Site
Winston-Salem, North Carolina, 27517

Other trials in United States

Canada6 sites

GSK Investigational Site
Greenfield Park, Quebec, J4V 2H1
GSK Investigational Site
Halifax, Nova Scotia, B3H 2Y9
GSK Investigational Site
Kingston, Ontario, K7L 2V7
GSK Investigational Site
Sainte-Foy, Quebec, G1V 4G5
GSK Investigational Site
Vancouver, British Columbia, V5Z 1M9
GSK Investigational Site
Vancouver, British Columbia, V6Z 1Y6

Other trials in Canada

About this study

Official title: A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury

The study has two parts: Part A will be an open-label investigation in five subjects. Part B will be a double-blind, placebo controlled investigation and will involve approximately 60 subjects.

Read the detailed description

The acute respiratory distress syndrome (ARDS) is a form of severe acute lung injury (ALI) characterized by hypoxemic respiratory failure (the lungs are unable to absorb oxygen to the arterial blood) and non-cardiogenic pulmonary edema (accumulation of fluid in the lungs). The syndrome may be caused by direct or indirect injury to the lungs. It is associated with a mortality rate of up to 40-50%. There are no marketed pharmacologic therapies for this devastating syndrome.

This study aims to assess the safety, tolerability and pharmacodynamics of GSK2586881, a recombinant human angiotensin converting enzyme type 2 (rhACE2).

ACE2 is involved in the Renin-Angiotensin System (RAS), which controls blood pressure, electrolytes and intravascular fluid volume. A key function of rhACE2 is believed to be the cleavage of Angiotensin II (Ang II) to Ang (1-7), which have opposing physiological roles. Elevated levels of Ang II are associated with vasoconstriction, inflammation, fibrosis, vascular leak, and sodium absorption. Ang (1-7) appears to be a counterregulatory protein in the RAS; associated with vasodilation, anti-proliferation, antiinflammation, and reduced vascular leak. It has been observed that levels of Ang II are increased in humans with ALI/ ARDS. It is expected that the reduction of Ang II should have a positive impact on ALI and ARDS.

Conditions: Lung Injury, Acute
Being tested: Dose 1 GSK2586881, Dose 2 GSK2586881, Dose 3 GSK2586881, Dose 4 GSK2586881, Placebo (saline)
Keywords: rhACE2, Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury, GSK2586881, critical care
Medical subject headings: Acute Lung Injury, Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dose 1 GSK2586881Drug
Low dose GSK2586881 administered intravenously
Dose 2 GSK2586881Drug
Medium dose GSK2586881 administered intravenously
Dose 3 GSK2586881Drug
Medium-High dose GSK2586881 administered intravenously
Dose 4 GSK2586881Drug
High dose GSK2586881 administered intravenously
Placebo (saline)Drug
Administered intravenously to match intervention

Study groups in NCT01597635
Study group	Role	What they receive
Part A	Experimental	4 increasing doses of GSK2586881 given over 2 days Receives: Drug: Dose 1 GSK2586881; Drug: Dose 2 GSK2586881; Drug: Dose 3 GSK2586881; Drug: Dose 4 GSK2586881
Part B	Experimental	Repeat Medium-High dose of GSK2586881 (or placebo) over 3 days Receives: Drug: Dose 3 GSK2586881; Drug: Placebo (saline)

What is being measured

The primary outcome is the main question the study is designed to answer.

Heart Rate Assessments Upto Day 7 (Part B)
Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Measured: Up to Day 7
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Measured: Up to Day 7
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Measured: Up to Day 7
Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Measured: Up to Day 7
Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Measured: Up to Day 7

Secondary outcomes (18)

Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part A
Measured: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part B.
Measured: Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)
Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
Measured: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours
Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)
Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
Measured: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)
Renin-angiotensin system cascade biomarkers included Ang II and Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.
Measured: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)
Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours on Day 1 and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.
Measured: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)
Renin-angiotensin system cascade biomarkers included Ang II, Ang (1-7) and Ang (1-5). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Measured: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B)
Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-5) and Ang II/Ang (1-7) and). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Measured: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B)
Measures of oxygenation included PEEP the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration, peak ventilator pressure highest level of pressure applied to the lungs during inhalation and plateau ventilatory pressure the pressure applied to small airways and alveoli measured during an inspiratory pause on the ventilator. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Measured: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B)
Measure of oxygenation included PaO2/FiO2 ratio defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen by pulse oximeter a device that measured the oxygen saturation of arterial blood in a participant by utilizing a sensor attached typically to a finger, toe, or ear to determine the percentage of oxyhemoglobin in blood pulsating through a network of capillaries.
Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Measured: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Measure of Oxygenation Index Upto Day 7 (Part B)
Oxygenation index was defined as calculation used in intensive care medicine to measure the fraction of inspired oxygen (FiO2) and its usage within the body and was computed using the equation Oxygenation Index= FiO2 x Mean Airway Pressure/Pao2. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Measured: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B)
The RIFLE score is made up of the glomerular filtration rate criteria (GFRC) and urine output criteria (UOC) and is defined as Risk (Serum Creatinine x 1.5 or GFR decrease > 25%-GFRC and < 0.5 milliliter/kilograms/hour [ml/kg/hour] x 6 hours-UOC), Injury (Serum Creatinine x 2 or GFR decrease > 50%-GFRC and < 0.5 ml/kg/hour x 12 hours), Failure (Serum Creatinine x 3, or GFR decrease > 75% [F=Failure] or Serum Creatinine >=4 milligrams/deciliter [mg/dl] with an acute rise > 0.5 mg/dl [Fc=Failure acute on chronic] and < 0.3 ml/kg/hour x 24 hours, or anuria x 12 hours [Fo=Failure oligouria]). Due to the duration of this study it was not possible to be calculate the designated RIFLE class Loss and RIFLE class End-stage kidney disease. Data has been presented for rifle score total, rifle score GFR and rifle score urine. Abbreviations NAKI= No acute kidney injury, R=risk, I=injury, MISS= Unable to derive score.
Measured: Upto Day 3
Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B)
The SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). The score ranges from 0-24. 0 (normal) to 4 (high degree of dysfunction) is given for each organ system, with a higher score indicating greater severity. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.
Measured: Day 4 and Day 7
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B)
Serum inflammatory biomarkers included CXCL-8 [IL-8], IL-6, markers of neutrophil activation included (e.g. myeloperoxidase [MPO]), markers of lung epithelial cell injury included receptor for advanced glycation end-products [RAGE], Angiopoietin 2, along with rennin, aldosterone levels. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Measured: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B)
Serum inflammatory biomarker included CRP. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Measured: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B)
Markers of lung epithelial cell injury included CCP16 and SP-D. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Measured: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A)
Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.
Measured: Follow-up (Day 14) and follow-up (Day 28)
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B)
Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.
Measured: Follow-up (Day 14 )and follow-up (Day 28)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 20126 Oct 2014

First posted14 May 2012 (estimated)
Study start1 Sep 2012
Primary completion1 Oct 2014
Study completion6 Oct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Lung Injury, AcuteStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01597635
Sponsor's protocol ID: 114622
Status last verified: Aug 2017
First submitted: 26 Jan 2012
Last updated: 28 Sep 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Khan A, Benthin C, Zeno B, Albertson TE, Boyd J, Christie JD, Hall R, Poirier G, Ronco JJ, Tidswell M, Hardes K, Powley WM, Wright TJ, Siederer SK, Fairman DA, Lipson DA, Bayliffe AI, Lazaar AL. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care. 2017 Sep 7;21(1):234. doi: 10.1186/s13054-017-1823-x.
PubMed 28877748

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Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Lung Injury, Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury
ClinicalTrials.gov ID: NCT01597635
Acronym / sponsor ID: 114622
Conditions: Lung Injury, Acute
Keywords: rhACE2, Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury, GSK2586881, critical care
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 Sep 2012
Primary completion: 1 Oct 2014 (actual)
Study completion: 6 Oct 2014 (actual)
First posted: 14 May 2012 (estimated)
Results: Posted 28 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study has two parts: Part A will be an open-label investigation in five subjects. Part B will be a double-blind, placebo controlled investigation and will involve approximately 60 subjects.

Detailed description

This study aims to assess the safety, tolerability and pharmacodynamics of GSK2586881, a recombinant human angiotensin converting enzyme type 2 (rhACE2).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Part A	Experimental	Drug: Dose 1 GSK2586881, Drug: Dose 2 GSK2586881, Drug: Dose 3 GSK2586881, Drug: Dose 4 GSK25868814 increasing doses of GSK2586881 given over 2 days
Part B	Experimental	Drug: Dose 3 GSK2586881, Drug: Placebo (saline)Repeat Medium-High dose of GSK2586881 (or placebo) over 3 days

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Male or female, 18 - 80 years of age (inclusive)
Diagnosis of ALI with acute onset of PaO2/FiO2 ratio less than or equal to 300, and bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric, and requirement for positive pressure ventilation via an endotracheal tube, and no clinical evidence of left atrial hypertension
Cause of ALI thought to be associated with infection, sepsis, pneumonia, aspiration, or similar as judged by the PI and/or medical monitor
The subject must be randomized into the study within 48 hours from the time of diagnosis of ALI
Period of hemodynamic stability (e.g. 4-6 hours) prior to the initiation of study treatment not requiring resuscitative measures with stable pressor requirements. In this study low-dose arginine vasopressin is not considered a pressor, and is permitted in Parts A and B.

Key exclusion criteria (28 listed)

Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.
Known positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody
Current or chronic history of liver disease (Child Pugh score of greater than or equal to 10), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Known history of substance abuse or alcohol abuse, within 6 months of the study causing chronic liver disease such as cirrhosis, chronic ascites or portal hypertension, or known evidence of withdrawal syndrome within the past 6 months.
The subject has participated in a clinical trial and has received 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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dose 1 GSK2586881Low dose GSK2586881 administered intravenously	Drug	Part A
Dose 2 GSK2586881Medium dose GSK2586881 administered intravenously	Drug	Part A
Dose 3 GSK2586881Medium-High dose GSK2586881 administered intravenously	Drug	Part A, Part B
Dose 4 GSK2586881High dose GSK2586881 administered intravenously	Drug	Part A
Placebo (saline)Administered intravenously to match intervention	Drug	Part B

Primary outcome

Heart Rate Assessments Upto Day 7 (Part B)
Time frame: Up to Day 7
Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
Time frame: Up to Day 7
Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
Time frame: Up to Day 7
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
Time frame: Up to Day 7
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
Time frame: Up to Day 7
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

18 secondary outcomes

Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
Time frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
Time frame: Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)
Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
Time frame: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours
Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)
Time frame: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)
Time frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)
Time frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)
Time frame: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B)
Time frame: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B)
Time frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B)
Time frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Measure of Oxygenation Index Upto Day 7 (Part B)
Time frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7
Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B)
Time frame: Upto Day 3
Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B)
Time frame: Day 4 and Day 7
Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B)
Time frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B)
Time frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B)
Time frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A)
Time frame: Follow-up (Day 14) and follow-up (Day 28)
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B)
Time frame: Follow-up (Day 14 )and follow-up (Day 28)

Results and safety

Results posted to the registry on 28 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A	5	2
Part B (Placebo BID)	0	0
Part B (GSK2586881 BID)	0	0

Primary outcome: Heart Rate Assessments Upto Day 7 (Part B)

Time frame: Up to Day 7. Mean (Standard Deviation). Unit: Beats per minute

Measure	Part B (Placebo BID) n = 20	Part B (GSK2586881 BID) n = 19
Heart rate on Day 1 at Pre-dose	87.4 (16.32)	97.7 (16.25)
Heart rate on Day 1 at 0.5 hours	87.9 (17.08)	95.3 (15.10)
Heart rate on Day 1 at 2 hours	88.8 (18.22)	94.7 (17.59)
Heart rate on Day 1 at 6 hours	90.0 (18.03)	96.5 (18.58)
Heart rate on Day 1 at 12 hours	87.6 (20.60)	97.1 (18.46)
Heart rate on Day 2 at 0 hours	92.2 (19.02)	93.4 (16.98)
Heart rate on Day 3 at 0 hours	93.3 (19.20)	97.7 (14.11)
Heart rate on Day 3 at 0.5 hours	91.7 (16.29)	97.2 (12.81)

Population analysed: The All Subjects - Part B Population was defined as all participants in Part B who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Primary outcome: Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)

Time frame: Up to Day 7. Mean (Standard Deviation). Unit: Millimeters of merucry

Measure	Part B (Placebo BID) n = 20	Part B (GSK2586881 BID) n = 19
Diastolic blood pressure on Day 1 at Pre-dose	64.7 (12.86)	53.9 (10.36)
Diastolic blood pressure on Day 1 at 0.5 hours	64.4 (13.75)	54.3 (11.39)
Diastolic blood pressure on Day 1 at 2 hours	64.4 (12.59)	54.8 (9.60)
Diastolic blood pressure on Day 1 at 6 hours	63.4 (12.08)	57.1 (9.21)
Diastolic blood pressure on Day 1 at 12 hours	64.3 (12.78)	57.6 (10.05)
Diastolic blood pressure on Day 2 at 0 hours	67.0 (15.17)	57.0 (10.22)
Diastolic blood pressure on Day 3 at 0 hours	63.9 (14.50)	62.7 (14.03)
Diastolic blood pressure on Day 3 at 0.5 hours	65.6 (13.21)	61.1 (12.83)

Population analysed: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Primary outcome: Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)

Time frame: Up to Day 7. Mean (Standard Deviation). Unit: millisecond

Measure	Part B (Placebo BID) n = 20	Part B (GSK2586881 BID) n = 19
PR interval on Day 1,Pre-dose	136.8 (24.19)	139.0 (25.09)
PR interval on Day 3,12 hours	128.5 (42.09)	149.3 (19.76)
PR interval at follow-up	140.4 (17.81)	144.8 (20.73)
QRS duration on Day 1,Pre-dose	98.0 (9.27)	95.5 (16.62)
QRS duration on Day 3,12 hours	82.8 (8.66)	98.8 (15.86)
QRS duration at follow-up Day 7	84.4 (9.01)	88.6 (16.86)
Uncorrected QT interval on Day 1,Pre-dose	350.0 (27.96)	357.5 (44.13)
Uncorrected QT interval on Day 3,12 hours	357.8 (48.90)	369.8 (33.92)

Population analysed: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

Primary outcome: Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)

Time frame: Up to Day 7. Mean (Standard Deviation). Unit: giga per liter

Measure	Part B (Placebo BID) n = 20	Part B (GSK2586881 BID) n = 19
Basophils on Day 1 at Pre-dose	0.020 (NA)	0.000 (0.0000)
Basophils on Day 3 at 12 hours	0.015 (0.0296)	0.011 (0.0277)
Basophils on Follow-up Day 7	0.025 (0.0431)	0.113 (0.1848)
Eosinophils on Day 1 at Pre-dose	0.110 (NA)	0.233 (0.4041)
Eosinophils on Day 3 at 12 hours	0.096 (0.1624)	0.163 (0.2280)
Eosinophils on Follow-up Day 7	0.137 (0.1074)	0.324 (0.4957)
Lymphocytes on Day 1 at Pre-dose	4.81 (4.603)	0.52 (0.266)
Lymphocytes on Day 3 at 12 hours	1.08 (0.948)	0.60 (0.380)

Population analysed: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: Upto follow-up Day 7.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A	3 of 5 (60%)	5 of 5 (100%)	3 of 5
Part B (Placebo BID)	4 of 20 (20%)	14 of 20 (70%)	2 of 20
Part B (GSK2586881 BID)	3 of 19 (15.8%)	15 of 19 (78.9%)	1 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28877748Khan A, Benthin C, Zeno B, Albertson TE, Boyd J, Christie JD, Hall R, Poirier G, Ronco JJ, Tidswell M, Hardes K, Powley WM, Wright TJ, Siederer SK, Fairman DA, Lipson DA, Bayliffe AI, Lazaar AL. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care. 2017 Sep 7;21(1):234. doi: 10.1186/s13054-017-1823-x.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

19 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dose 1 GSK2586881, Dose 2 GSK2586881 and Dose 3 GSK2586881 in people with Lung Injury, Acute, run by GlaxoSmithKline at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Heart Rate Assessments Upto Day 7 (Part B) (time frame: Up to Day 7). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01597635, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2017.