Study Evaluating Single Dose Of ILV-095 In Psoriasis Subjects

A SINGLE DOSE STUDY OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND CLINICAL ACTIVITY OF ILV-095 ADMINISTERED SUBCUTANEOUSLY TO SUBJECTS WITH PSORIASIS.

The purpose of this research study is to evaluate the safety and tolerability of ILV-095 when it is given to individuals with moderate to severe chronic plaque psoriasis. Another purpose of the study is to observe how the drug enters the blood and tissues over time, how the body breaks down the drug and whether or not the body will develop an immune reaction (sensitivity) to the drug.

Study Overview

• Status: Terminated
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: ILV-095 300 mg in a 4 to 1 ratio; Drug: ILV-095 300 mg in a 4 to 1 ratio

Detailed Description

B1991002 study is a phase 1 adaptive design study which terminated on 14Mar2011. Regular analyzes of psoriasis assessments conducted per the statistical plan indicate that even if every patient enrolled for the rest of the study respond (up to 23 additional subjects), the study can not meet its primary efficacy endpoint. Pfizer Inc. has terminated the trial and clinical team is asking all clinical investigators to continue collecting safety, pharmacokinetics and pharmacodynamics data until the last subject last visit for all subjects who received test article. Last Subject Last Visit occurred 20May2011.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1C 2H5
      • NewLab Clinical Research Inc
  • Ontario
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
• United States
  • Florida
    • Miami Gardens, Florida, United States, 33169
      • Cetero Research
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research
    • South Miami, Florida, United States, 33143
      • Miami Research Associates, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group, LLC
  • Michigan
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest University Health Sciences
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sexually active men or women must agree to use a medically acceptable form of contraception during the study and continue it for 16 weeks after investigational product administration.
• Negative urine pregnancy test result for all women.
• Body mass index (BMI) >=18 kg/m2 and body weight >=50 kg. BMI is calculated by taking the subject's weight, in kilograms, divided by the square of the subject's height, in meters, at screening: BMI = weight (kg)/(height [m]).
• Must meet the following criteria for disease activity, at screening and/or at study entry (subjects who washout from prior therapy may not meet this level of disease activity at screening but must before being entered into the study).
• Must have stable moderate to severe chronic plaque psoriasis covering >=15% of body surface area and be a candidate for systemic therapy or phototherapy.
• Psoriasis Area Severity Index (PASI) score of >11.
• Physician Global Assessment (PGA) of psoriasis score >=3.
• Target lesion score >=6 based on the physician rating of selected sites for erythema, plaque elevation and scaling, with a minimum of 2 on the plaque elevation score. A-12-point score will be used with a 1-4 scale for each domain. Target lesions should not be on the scalp, axillae, face, or groin.

Exclusion Criteria:

• Presence or history of any disorder that may prevent the successful completion of the study.
• Evidence of unstable clinically significant disease (eg, unstable cardiovascular, renal, respiratory, or psychiatric disease or any serious disorder that currently requires physician care).
• Acute disease state (eg, nausea, vomiting, fever, or diarrhea) within 7 days before study day 1.
• Evidence of skin conditions (eg, eczema) other than psoriasis that would interfere with evaluations of the effect of study medication on psoriasis.
• Presence of guttate, erythrodermic, or pustular psoriasis.
• Active severe infections within 4 weeks before study day 1.
• Systemic malignancy within the past 5 years including melanoma. Treated skin cancer (basal cell carcinoma or squamous cell carcinoma) is excluded.

Evidence of latent tuberculosis by purified protein derivative (PPD) screening. PPD screening should be performed according to local standards using the tuberculin skin test (TST). Any result >5mm is considered positive. Prior Bacillus Calmette-Guerin (BCG) should not be taken into account when interpreting a TST result. TST must be performed during the screening period unless one has been performed within the previous 3 months and the results are available.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: ILV-095 300 mg in a 4 to 1 ratio; Single dose of ILV-095 300 mg; Drug: ILV-095 300 mg in a 4 to 1 ratio; Single dose of Placebo
Active Comparator: ILV-095	Drug: ILV-095 300 mg in a 4 to 1 ratio; Single dose of ILV-095 300 mg; Drug: ILV-095 300 mg in a 4 to 1 ratio; Single dose of Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With 50 Percent Improvement From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 2	PASI score: combined assessment of lesion severity and area affected into single score range:0 (no disease) to 72(maximal disease),with higher scores representing 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 to 100 percent involvement),severity estimated by clinical signs:erythema(E),infiltration(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. Percentage of participants with at least 50 percent(%) improvement in total PASI score at Week 2 relative to baseline total PASI score was reported and 95% confidence interval was calculated using Clopper-Pearson (exact) method.	Baseline, Week 2
Percentage of Participants With 50 Percent Improvement From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 4	PASI score: combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72(maximal disease), with higher scores representing 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 to 100 percent involvement),severity estimated by clinical signs: erythema(E),infiltration(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. Percentage of participants with at least 50% improvement in total PASI score at Week 4 relative to baseline total PASI score was reported and 95% confidence interval was calculated using Clopper-Pearson (exact) method.	Baseline, Week 4
Percentage of Participants With 50 Percent Improvement From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 6	PASI score: combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72(maximal disease), with higher scores representing 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 to 100 percent involvement),severity estimated by clinical signs: erythema(E),infiltration(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. Percentage of participants with at least 50% improvement in total PASI score at Week 6 relative to baseline total PASI score was reported and 95% confidence interval was calculated using Clopper-Pearson (exact) method.	Baseline, Week 6
Percentage of Participants With 50 Percent Improvement From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 8	PASI score: combined assessment of lesion severity and area affected into single score range: 0 (no disease) to 72(maximal disease), with higher scores representing 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 to 100 percent involvement),severity estimated by clinical signs: erythema(E),infiltration(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. Percentage of participants with at least 50% improvement in total PASI score at Week 8 relative to baseline total PASI score was reported and 95% confidence interval was calculated using Clopper-Pearson (exact) method.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
To provide safety, tolerability, PK, PD and immunogenicity profiles of a single dose of ILV-095 in subjects with psoriasis using, adverse event collection, injection site reaction, actual times of sample collection and IL-22 analysis.	56 days for each treatment group

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Lesion Score (TLS)	Each lesion was evaluated for 3 components: erythema, plaque elevation, and scaling. Physician rated each component using the following scale: 0= none, 1= mild, 2= moderate, 3= severe and 4= very severe, where higher scores indicated higher lesion severity. TLS was calculated as the sum of the 3 individual components and TLS total score ranged from 0 (no disease) to 12 (maximal disease severity), where higher scores indicated more severity.	Pre-treatment (Day -1), Week 2, 4, 6, 8
Physician Global Assessment (PGA) Score of Psoriasis	PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema (E), infiltration (I), and scaling (S) across all psoriatic lesions. The severity rating scores (erythema: 0= no evidence of erythema to 4= dark, deep red; infiltration: 0= no evidence of plaque elevation to 4= marked plaque elevation, hard/sharp borders; scaling: 0= no evidence of scaling to 4= thick, coarse scale predominates) were summed (E + I + S = total) and the average (total score divided by 3) was calculated. The average was rounded to the nearest whole number score to determine the PGA. The 5-point scale for PGA was ranging from: 0= clear; 1= almost clear; 2= mild; 3= moderate; 4= severe, where higher scores indicated more severity.	Pre-treatment (Day -1), Week 2, 4, 6, 8
Number of Participants With Laboratory Abnormalities of Potential Clinical Importance	Hematology (decrease of greater than or equal to [>=] 5% hematocrit, hemoglobin >=20 gram per liter [g/L]; white blood cell less than [<] 3.0*10^9/L; neutrophil <1.5*10^9/L; platelet <100*10^9 /L; eosinophil greater than [>] 0.5*10^9/L); coagulation (prothrombin, partial thromboplastin time >1.5*upper limit of normal [ULN]); chemistry (above ULN or below lower limit of normal [LLN] for [sodium >5 millimole per liter {mmol/L}; potassium >0.5 mmol/L; glucose {fasting} >0.83 mmol/L; glucose {non fasting} >5.0 mmol/L; phosphorus >0.162 mmol/L]; creatinine >1.36*ULN; blood urea nitrogen/urea >1.5*ULN; creatine kinase >3*ULN; change from baseline in [calcium >=0.25 mmol/L; magnesium >=0.21 mmol/L; total protein >=20 g/L; albumin >=10 g/L; uric acid >0.119 mmol/L]; fasting [cholesterol >7.77 mmol/L; triglyceride >3.39 mmol/L]); liver test (alanine amino [A] transferase [T], aspartate AT, total bilirubin >2*ULN; alkaline phosphatase >1.5*ULN; gamma glutamyl T, lactate dehydrogenase >3*ULN).	Baseline (Day 1) up to Week 16
Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance	Sitting and supine systolic blood pressure (BP): increase of >=20 millimeter mercury (mm Hg) from baseline value and >=160 mm Hg; decrease of >=20 mm Hg from baseline value and less than or equal to (<=) 90 mm Hg. Diastolic BP: increase of >=15 mm Hg from baseline value and >=100 mm Hg; decrease of >=15 mm Hg from baseline value and <=50 mm Hg. Heart rate: increase of >15 beats per minute (bpm) from baseline value and >=120 bpm; decrease of >15 bpm from baseline value and <=45 bpm. Orthostatic (supine to standing): 1) systolic BP: decrease of >=20 mm Hg from supine value; 2) diastolic BP: decrease of >=20 mm Hg from supine value; 3) heart rate: increase of >=30 bpm from supine value. Oral temperature <35 degree Celsius or >38.3 degree Celsius. Respiratory rate <10 breaths per minute; >25 breaths per minute. Weight >=7% increase or decrease from baseline value.	Baseline (Day 1) up to Week 16
Number of Participants With Electrocardiograms (ECG) Abnormalities of Potential Clinical Importance	Criteria for abnormality of potential clinical importance: PR interval: change of >=20 milliseconds (msec) from baseline value and >=220 msec; QRS interval: >=120 msec; corrected QT (QTc) interval (men): >450 msec and QTc interval (women): >470 msec.	Baseline (Day 1) up to Week 16
Maximum Observed Serum Concentration (Cmax) of ILV-095		Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Time to Reach Maximum Observed Serum Concentration (Tmax) of ILV-095		Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Serum Terminal Half-Life (t1/2) of ILV-095	t1/2 was the time measured for the serum concentration of ILV-095 to decrease by one half.	Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of ILV-095	AUCinf was calculated as AUClast + (Clast/kel), where AUClast was area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (Clast) and Kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Area Under the Serum Concentration-Time Curve From Time Zero to Time of The Last Quantifiable Concentration (AUClast) of ILV-095	AUClast was the area under the serum concentration versus time curve from time zero to the time of the last quantifiable concentration (Clast).	Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Apparent Clearance (CL/F) of ILV-095	Clearance was a quantitative measure of the rate at which ILV-095 was removed from the blood (rate at which ILV-095 was metabolized or eliminated by normal biological processes).	Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Apparent Volume of Distribution (Vz/F) of ILV-095	Apparent volume of distribution was defined as the theoretical volume in which the total amount of ILV-095 was needed to be uniformly distributed to produce the desired serum concentration of ILV-095.	Pre-dose, 2, 4, 8, 24, 48, 120, 216, 312, 480, 648, 984, 1320, 1656, 1992, 2328, 2664 hours post-dose
Serum Amyloid-A Levels	Serum amyloid-A (SAA) is a low molecular weight acute phase protein. Serum samples were analyzed for SAA concentrations using solid phase sandwich enzyme-linked immunosorbent assay. The limit of detection (LOD) for SAA assay was 0.21 ng/mL.	Baseline, Day 14, 56,112
Plasma Interleukin-6 (IL-6) Levels	Interleukin: group of naturally occurring proteins that are particularly important in stimulating immune responses such as inflammation. Plasma samples were analyzed for IL-6 concentrations using high sensitive enzyme-linked immunosorbent assay. The limit of detection for IL-6 assay was 0.00002 ng/mL.	Baseline, Day 14, 56,112
Plasma Interleukin-22 (IL-22) Levels	Interleukin: group of naturally occurring proteins that are particularly important in stimulating immune responses such as inflammation. Plasma samples were analyzed for IL-22 concentrations using highly sensitive enzyme-linked immunosorbent assay. The lower limit of quantification for IL-22 assay was 0.34 pg/mL.	Baseline, Day 14, 56,112
Serum C-Reactive Protein (CRP) Levels	CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Serum samples were analyzed for CRP concentrations using nephelometry.	Baseline, Day 14, 56,112
Number of Participants With Positive Anti-Drug Antibodies of ILV-095	The serum samples were analyzed for anti-drug antibodies of ILV-095 by a validated electrochemiluminescence assay and participants with positive anti-drug antibodies were reported in this outcome measure.	Baseline up to Week 16
Number of Participants With Injection-Site Reactions	Injection site reactions included following symptoms: injection site itching, injection site redness, injection-site swelling, injection site pain, injection site ulceration, requirement for plastic surgery associated with an injection.	Baseline up to Week 16

Collaborators and Investigators

• Sponsor: 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 1, 2009
• Primary Completion (Actual): May 20, 2011
• Study Completion (Actual): May 20, 2011

Study Registration Dates

• First Submitted: November 6, 2009
• First Submitted That Met QC Criteria: November 9, 2009
• First Posted (Estimated): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Single dose psoriasis study
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 3226K1-1002; B1991002 (Other Identifier: Alias Study 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.