Study Evaluating The Safety And Tolerability Of ILV-094 In Subjects With Psoriasis
- Registration Number
- NCT00563524
- Lead Sponsor
- Wyeth is now a wholly owned subsidiary of Pfizer
- Brief Summary
The purpose of this study is to assess safety, and tolerability of multiple doses of ILV-094 administered to subjects with psoriasis
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
- Men and Women of nonchildbearing potential 18 years or older.
- Physician Area and Severity Index (PASI) greater than 11.
- Physician Global Assessment (PGA) greater than 3.
- Use of any investigational small -molecule drug within 30 days before the first dose of test article administration, and use of any investigational biologic agents within 5 half lives before study day 1, or 90 days for investigational biologics that may have a long clinical duration of effect.
- Live vaccines within 3 months before test article administration or during the study.
- Use of any biologic therapy within approximately 5 half-lives before test article administration. Approximate half-lives of biologic therapies approved for psoriasis are as follows: Enbrel, 5 days; Humira, 14 days; Remicade, 9 days; Amevive, 12 days; Raptiva, 6 days. It is recommended that Amevive be discontinued for at least 90 days because of its long clinical duration of action.
- Psoralen plus ultraviolet A radiation (PUVA) therapy within 4 weeks before study day 1.
- Ultraviolet B (UVB) therapy within 2 weeks before study day 1.
- Receipt of systemic psoriasis therapy (eg, oral retinoids, methotrexate, hydroxyurea, cyclosporine, or azathioprine) or systemic corticosteroids within 4 weeks before study day 1.
- Topical steroids, topical vitamin A or D analog preparations, or anthralin within 2 weeks before study day 1. (Exception: topical therapies, including steroids at no higher than mild strength [class 6 or 7 topical corticosteroids], are permitted on the scalp, axillae, face, and groin, but the dose of the medication must be kept stable throughout the trial.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 ILV-094 -
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) Day 1 up to Day 126 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.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Day 1 up to Day 126 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.
Number of Participants With Laboratory Test Values of Potential Clinical Importance Day 1 up to Day 126 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.
Number of Participants With Vital Sign Values of Potential Clinical Importance (PCI) Day 1 up to Day 126 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.
- Secondary Outcome Measures
Name Time Method Terminal-phase Disposition Rate Constant of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14 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.
Terminal Half-Life (t1/2) of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14 Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to 312 Hours [AUC (0-312)] Postdose of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312 hours post-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.
Average Observed Plasma Concentration (Cavg) of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14 Cavg was the average plasma concentration of drug during the dosing interval.
Serum C-Reactive Protein (CRP) Levels Day 1, 14, 28, 42, 56 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.
Accumulation Ratio (Rac) of ILV-094 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 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 to Reach Maximum Observed Plasma Concentration (Tmax) of ILV-094: Multiple Dose 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 Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1 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.
Terminal Half-Life (t1/2) of ILV-094: Single Dose Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1 Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Serum Interleukin-6 (IL-6) Levels Day 1, 14, 28, 42, 56 Serum Amyloid-A Levels Day 1, 14, 28, 42, 56 Maximum Observed Plasma Concentration (Cmax) of ILV-094: Single Dose 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 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 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 The Time of Last Quantifiable Concentration (AUClast) of ILV-094: Single Dose Pre-dose, 1, 2, 3, 4, 8, 24, 48, 96, 144, 192, 240, 312 hours post-dose on Day 1 AUClast is defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration.
Apparent Clearance of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14 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.
Apparent Volume of Distribution of ILV-094: Multiple Dose Pre-dose, 1, 2, 3, 4, 8, 24, 28, 96,144, 192, 240, 312, 480, 648, 816 hours post-dose on Day 14 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.
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Scores at Week 2, 4, 6, 8 and 12 Baseline, Week 2, 4, 6, 8, 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).
Percent Change From Baseline in Target Lesion Score (TLS) at Week 2, 4, 6, 8 and 12 Baseline, Week 2, 4, 6, 8, 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.
Percent Change From Baseline in Physician Global Assessment Score at Week 2, 4, 6, 8 and 12 Baseline, Week 2, 4, 6, 8, 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.
Trial Locations
- Locations (24)
Hudson Dermatology
🇺🇸Evansville, Indiana, United States
Dawes Fretzin Clinical Research Group
🇺🇸Indianapolis, Indiana, United States
Baylor Research Institute
🇺🇸Dallas, Texas, United States
FARMOVS Parexel (Pty) Ltd
🇿🇦Bloemfontein, Free State, South Africa
David Stoll, MD
🇺🇸Beverly Hills, California, United States
Dermatology Research
🇺🇸Santa Monica, California, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Duke Clinical Reseach Unit
🇺🇸Durham, North Carolina, United States
Central Dermatology
🇺🇸Saint Louis, Missouri, United States
New York University Medical Center
🇺🇸New York, New York, United States
Dawes Fretzin Dermatology Group
🇺🇸Indianapolis, Indiana, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Innovaderm Recherches Inc
🇨🇦Montreal, Quebec, Canada
MRA Clinical Research
🇺🇸South Miami, Florida, United States
Queen Mary Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong
Stratical Medical
🇨🇦Edmonton, Alberta, Canada
University of Alberta, Hospital Site Clinical Sciences Building
🇨🇦Edmonton, Alberta, Canada
Parexel George
🇿🇦George, Western Cape, South Africa
The Northern Alberta Clinical Trials and Research Centre (NACTRC)
🇨🇦Edmonton, Alberta, Canada
Hamzavi Dermatology
🇺🇸Fort Gratiot, Michigan, United States
K. Papp Clinical Research
🇨🇦Waterloo, Ontario, Canada
Bio Pharma Services Inc
🇨🇦Toronto, Ontario, Canada
Miami Research Associates
🇺🇸South Miami, Florida, United States