The purpose of this study is to assess safety, and tolerability of multiple doses of ILV-094 administered to subjects with psoriasis
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
76
SC and IV administration on days 1, 14, 28, and 42
David Stoll, MD
Beverly Hills, California, United States
Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug to the end of study (Day 126), that were absent before treatment or that worsened relative to pre-treatment state. AEs include both SAEs and all non-SAEs.
Time frame: Day 1 up to Day 126
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Clinically significant ECG findings included: heart rate (HR): less than or equal to (\<=) 45 beats per minute (bpm) or greater than or equal to (\>=)120 bpm or decrease/increase of \>=15 bpm from baseline value, PR interval: \>=220 millisecond (msec) and change of \>=20 msec from baseline value and; QRS interval \>=120 msec; corrected QT (QTc) interval for men greater than (\>) 450 msec, QTc interval for women \>470 msec.
Time frame: Day 1 up to Day 126
Number of Participants With Vital Sign Values of Potential Clinical Importance (PCI)
Criteria for identifying vital sign values of PCI: heart rate: increase of \>15 bpm from baseline value and \>=120 bpm and decrease of \>15 bpm from baseline value and \<=45 bpm; Sitting and Supine systolic blood pressure (SBP): increase of \>=20 millimeters of mercury (mm Hg) from baseline value and \>=160 mm Hg and decrease of \>=20 mm Hg from baseline value and \<=90 mm Hg; Sitting and Supine diastolic blood pressure (DBP): increase of \>=15 mm Hg from baseline value and \>=100 mm Hg and decrease of \>=15 mm Hg from baseline value and \<=50 mm Hg; Respiratory rate: \<10 or \>25 breaths/minute; Weight: \>=7 percent increase or decrease from baseline value; Oral temperature: \<35 degree Celsius (C) or \>38.3 degree C.
Time frame: Day 1 up to Day 126
Number of Participants With Laboratory Test Values of Potential Clinical Importance
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Dermatology Research
Santa Monica, California, United States
Miami Research Associates
South Miami, Florida, United States
MRA Clinical Research
South Miami, Florida, United States
Hudson Dermatology
Evansville, Indiana, United States
Dawes Fretzin Clinical Research Group
Indianapolis, Indiana, United States
Dawes Fretzin Dermatology Group
Indianapolis, Indiana, United States
Hamzavi Dermatology
Fort Gratiot, Michigan, United States
Central Dermatology
St Louis, Missouri, United States
New York University Medical Center
New York, New York, United States
...and 14 more locations
Criteria:Hematocrit:5% decrease from baseline,Hemoglobin:decrease of \>=20 gram per liter(g/L) from baseline,WBC: \<3.0\*10\^9/L;neutrophils: \<1.5\*10\^9/L,platelet count:\<100\*10\^9/L,eosinophils: \>0.5\*10\^9/L;prothrombin time,partial thromboplastin time: \>1.5\*Upper limit of normal(ULN);sodium,potassium: \>5millimoles per liter(mmol/L)aboveULN/below lower limit of normal(LLN),creatinine: \>1.36\*ULN,urea: \>1.5\*ULN,glucose(fasting): \>0.83mmol/L above ULN/below ULN,glucose (non-fasting): \>5.0 mmol/L above ULN/\>0.56 mmol/L below LLN,calcium:change of \>=0.25 mmol/L from baseline,magnesium:change at \>=0.21mmol/L from baseline value,phosphorus:\>0.162 mmol/L above ULN/below LLN,total protein:change of \>=20 g/L from baseline,albumin:change of \>=10 g/L from baseline,uric acid:change of \>0.119mmol/L from baseline,creatine kinase: \>3\*ULN,cholesterol: \>7.77mmol/L,triglycerides:\>3.39mmol/L;ALT,AST,total bilirubin: \>2\*ULN,alkaline phosphatase: \>1.5\*ULN,Gamma-glutamyl transferase,lactate dehydrogenase: \>3\*ULN.
Time frame: Day 1 up to Day 126
Maximum Observed Plasma Concentration (Cmax) of ILV-094: Single Dose
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of ILV-094: Multiple Dose
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ILV-094: Single Dose
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ILV-094: Multiple Dose
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Terminal-phase Disposition Rate Constant of ILV-094: Single Dose
The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations, expressed in 1/day.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1
Terminal-phase Disposition Rate Constant of ILV-094: Multiple Dose
The terminal-phase disposition rate constant measured by a log-linear regression of the terminal mono exponential portion of the observed plasma concentrations, expressed in 1/day.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Terminal Half-Life (t1/2) of ILV-094: Single Dose
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1
Terminal Half-Life (t1/2) of ILV-094: Multiple Dose
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Area Under the Curve From Time Zero to The Time of Last Quantifiable Concentration (AUClast) of ILV-094: Single Dose
AUClast is defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1
Area Under the Curve From Time Zero to 312 Hours [AUC (0-312)] Postdose of ILV-094: Multiple Dose
AUC (0-312) = Area under the plasma concentration time-curve from time zero (pre-dose) to 312 hours (0-312) postdose of ILV-094.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312 hours post-dose
Apparent Clearance of ILV-094: Multiple Dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after IV dose (apparent clearance) was influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Apparent Volume of Distribution of ILV-094: Multiple Dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Average Observed Plasma Concentration (Cavg) of ILV-094: Multiple Dose
Cavg was the average plasma concentration of drug during the dosing interval.
Time frame: Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14
Accumulation Ratio (Rac) of ILV-094
Rac was estimated as: X\*AUClast of Day 1 divided by AUC312 of Day 42, where X is the ratio of the maintenance dose to the loading dose of ILV-094, AUClast is defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration and AUC-312 is the AUC from time 0 to 312 hours on Day 42.
Time frame: Day 1: pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose; Day 42: pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312 hours post-dose
Serum C-Reactive Protein (CRP) Levels
CRP is an acute-phase protein which provides an objective criterion of inflammatory activity. Normal range of CRP is 0 milligram per deciliter (mg/dL) to 1 mg/dL. A decrease in the level of CRP indicates reduction in inflammation.
Time frame: Day 1, 14, 28, 42, 56
Serum Interleukin-6 (IL-6) Levels
Time frame: Day 1, 14, 28, 42, 56
Serum Amyloid-A Levels
Time frame: Day 1, 14, 28, 42, 56
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Scores at Week 2, 4, 6, 8 and 12
PASI score is the combined assessment of lesion severity and area affected into single score range on a scale of 0 (no disease) to 72 (maximal disease), with higher scores indicating greater severity of psoriasis. Body divided into 4 sections (head and neck \[h\], arms \[u\], trunk \[t\], legs \[l\]); each area scored by itself and scores combined for final PASI score. For each section, percent body surface area (A) of skin involved was estimated: 0 (no involvement) to 6 (90-100 percent involvement), severity estimated by clinical signs: erythema (E), induration (I), scaling (S); 5 point scale: 0 (no involvement) to 4 (very marked involvement). Final PASI score = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl), where head: 0.1; upper limbs: 0.2; trunk: 0.3; lower limbs: 0.4).
Time frame: Baseline, Week 2, 4, 6, 8, 12
Percent Change From Baseline in Target Lesion Score (TLS) at Week 2, 4, 6, 8 and 12
TLS was based on the severity of 3 components: erythema, induration, and scaling. Severity of each component was evaluated on a 5-point scale as: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked, with higher scores reflected increased lesion severity. Scores of 3 components were summed to derive the total target lesion score, ranging from 0=none to 12=very marked, with higher scores reflected increased lesion severity.
Time frame: Baseline, Week 2, 4, 6, 8, 12
Percent Change From Baseline in Physician Global Assessment Score at Week 2, 4, 6, 8 and 12
Physician global assessment of disease activity was measured on an 11-point scale, ranging from 0 = no disease activity to 10 = extreme disease activity, where higher scores indicating greater disease activity.
Time frame: Baseline, Week 2, 4, 6, 8, 12