Study Evaluating The Safety And Tolerability Of ILV-094 In Subjects With Psoriasis

AN ASCENDING MULTIPLE DOSE STUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND CLINICAL EFFICACY OF ILV-094 ADMINISTERED SUBCUTANEOUSLY OR INTRAVENOUSLY TO SUBJECTS WITH PSORIASIS

The purpose of this study is to assess safety, and tolerability of multiple doses of ILV-094 administered to subjects with psoriasis

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: ILV-094

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratical Medical
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta, Hospital Site Clinical Sciences Building
    • Edmonton, Alberta, Canada, T6G 2C8
      • The Northern Alberta Clinical Trials and Research Centre (NACTRC)
  • Ontario
    • Toronto, Ontario, Canada, M9L 3A2
      • Bio Pharma Services Inc
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
  • Quebec
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Recherches Inc
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • FARMOVS Parexel (Pty) Ltd
  • Western Cape
    • George, Western Cape, South Africa, 6529
      • Parexel George
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • David Stoll, MD
    • Santa Monica, California, United States, 90404
      • Dermatology Research
  • Florida
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Hudson Dermatology
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Dermatology Group
  • Michigan
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Central Dermatology
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Reseach Unit
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635-0909
      • Altoona Center for Clinical Research
  • Texas
    • Dallas, Texas, United States, 75246-1613
      • Baylor Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1	Drug: ILV-094; SC and IV administration on days 1, 14, 28, and 42; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Day 1 up to Day 126
Number of Participants With Laboratory Test Values of Potential Clinical Importance	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.	Day 1 up to Day 126

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Day 1, 14, 28, 42, 56
Serum Interleukin-6 (IL-6) Levels		Day 1, 14, 28, 42, 56
Serum Amyloid-A Levels		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).	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.	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.	Baseline, Week 2, 4, 6, 8, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Positive Anti-Drug Antibodies Response	Participants with their ADA titer levels >=6.23 were considered to be ADA positive. Participants with at least 1 positive ADA titer are reported.	Day 1 up to Day 126

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2007
• Primary Completion (Actual): June 14, 2010
• Study Completion (Actual): June 14, 2010

Study Registration Dates

• First Submitted: November 21, 2007
• First Submitted That Met QC Criteria: November 23, 2007
• First Posted (Estimated): November 26, 2007

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Dermatologic Agents; Fezakinumab
• Other Study ID Numbers: 3199K2-1105; B1981002 (Other Identifier: Alias Study Number); 2009-012554-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.