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A Study of Efalizumab in Participants With Moderate to Severe Chronic Psoriasis Who Have Failed, Have a Contraindication to, or Are Intolerant of Other Systemic Therapies

Primary Purpose

Psoriasis

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Efalizumab - anti-CD11a recombinant human monoclonal antibody
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis focused on measuring Candidates for systemic therapy for psoriasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Moderate to severe plaque psoriasis participants who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA Age at least 18 years For women of childbearing potential and for men whose partner can become pregnant, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study and up to 3 months after the last dose of efalizumab Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care Discontinuation of any systemic psoriasis treatment prior to commencement of the study drug. No washout period is required for these agents prior to starting study and receiving first dose of study drug (efalizumab) Discontinuation of all biologic agents (other than efalizumab) 3 months prior to receiving first dose of study drug (efalizumab) Discontinuation of any investigational drug or treatment 3 months prior to Study Day 0 or as per washout requirements from previous protocol No primary vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug The participant must be willing and able to comply with the protocol requirements for the duration of the study Exclusion Criteria: Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis Participants who have previously been on efalizumab treatment who withdrew due to lack of efficacy or an adverse event. If withdrawal was due to another non-drug reason (vaccination, or infection) then the patient can be included in this study History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection History of opportunistic infections (eg, systemic fungal infections, parasites) Seropositivity for human immunodeficiency virus (HIV). Participants will undergo mandatory testing at screening. Participants who are positive for HIV will be excluded Pregnancy or breast feeding White Blood Cell (WBC) count less than (<) 4*10^9 per liter or greater than (>) 14*10^9 per liter Participants with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count <100*10^9 per liter Seropositivity for hepatitis B or C virus. Participants will undergo testing at screening. Participants who are positive for hepatitis B antigen or hepatitis C antibody will be excluded History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to Study Day 0. Chest X-ray (within 3 months prior to Study Day 0) is required for high-risk participants. Participants with a positive chest X-ray will be excluded Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Participants with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year Any medical condition that, in the judgment of the investigator, would jeopardize the participant's safety following exposure to study drug

Sites / Locations

  • Medical Information

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Efalizumab

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants With Physician's Global Assessment (PGA) Ratings of Good or Better (FT)
The PGA assesses the global response of all psoriatic lesions to therapy by comparing the participant's present condition to baseline. PGA response includes: Cleared (100 percent [%] improvement; remission of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Excellent (75% to 99% improvement of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Good (50% to 74% improvement of all clinical signs and symptoms); Fair (25% to 49% improvement of all clinical signs and symptoms); Slight (1% to 24% improvement of all clinical signs and symptoms); Unchanged (clinical signs and symptoms unchanged); Worse (clinical signs and symptoms deteriorated). Percentage of participants with PGA ratings of Good or Better (i.e, Good, Excellent or Cleared) are reported.

Secondary Outcome Measures

Percentage of Participants With Psoriasis Rebound
Rebound was defined as worsening of disease as assessed by Psoriasis Area and Severity Index (PASI) score >125% of baseline or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 2 months of stopping therapy. PASI is an instrument used to assess the extent of cutaneous psoriasis and to measure the effects of therapy. The PASI divides the body into four anatomical regions: head, trunk, upper limbs, and lower limbs. For each region, the evaluator assesses the severity of erythema, induration/thickness and scaling and determines the percentage of the region affected by disease. A numerical PASI score is derived that evaluates the severity of symptoms in terms of the total body surface area affected. Total PASI score ranges from 0 to 72, with higher scores indicating more severe disease.
Percentage of Participants With Psoriasis Exacerbation
Exacerbation was defined as disease worsening either during or after treatment which was more inflammatory in nature compared to baseline and occurred either within pre-existing plaques, at previously uninvolved sites, or as new morphologies of disease.

Full Information

First Posted
November 4, 2005
Last Updated
August 24, 2017
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00249808
Brief Title
A Study of Efalizumab in Participants With Moderate to Severe Chronic Psoriasis Who Have Failed, Have a Contraindication to, or Are Intolerant of Other Systemic Therapies
Official Title
A Multicentre, Open Label Phase IIIb/IV Study of Subcutaneously Administered Efalizumab in the Treatment of Adult Patients With Moderate to Severe Chronic Plaque Psoriasis Who Have Failed to Respond to, or Who Have a Contraindication to, or Are Intolerant to Other Systemic Therapies Including Ciclosporin, Methotrexate and PUVA
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 13, 2004 (Actual)
Primary Completion Date
January 25, 2007 (Actual)
Study Completion Date
January 25, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary
This is a Phase IIIb/IV, open label, multicentre study of efalizumab (anti cluster of differentiation [CD] 11a recombinant human monoclonal antibody) in participants with moderate to severe plaque psoriasis who have failed to respond to, have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate, and psoralen and ultraviolet A phototherapy (PUVA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
Candidates for systemic therapy for psoriasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1266 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Efalizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Efalizumab - anti-CD11a recombinant human monoclonal antibody
Intervention Description
Participants will receive efalizumab 1.0 milligram per kilogram (mg/kg) (with an initial conditioning dose of 0.7 mg/kg) once weekly by subcutaneous injection for 12 weeks (first treatment [FT]). Depending on the response at Week 12, participants could receive additional 8 to 12 weekly injections of efalizumab 1.0 mg/kg.
Primary Outcome Measure Information:
Title
Percentage of Participants With Physician's Global Assessment (PGA) Ratings of Good or Better (FT)
Description
The PGA assesses the global response of all psoriatic lesions to therapy by comparing the participant's present condition to baseline. PGA response includes: Cleared (100 percent [%] improvement; remission of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Excellent (75% to 99% improvement of all clinical signs and symptoms, except for residual manifestations such as mild erythema); Good (50% to 74% improvement of all clinical signs and symptoms); Fair (25% to 49% improvement of all clinical signs and symptoms); Slight (1% to 24% improvement of all clinical signs and symptoms); Unchanged (clinical signs and symptoms unchanged); Worse (clinical signs and symptoms deteriorated). Percentage of participants with PGA ratings of Good or Better (i.e, Good, Excellent or Cleared) are reported.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With Psoriasis Rebound
Description
Rebound was defined as worsening of disease as assessed by Psoriasis Area and Severity Index (PASI) score >125% of baseline or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 2 months of stopping therapy. PASI is an instrument used to assess the extent of cutaneous psoriasis and to measure the effects of therapy. The PASI divides the body into four anatomical regions: head, trunk, upper limbs, and lower limbs. For each region, the evaluator assesses the severity of erythema, induration/thickness and scaling and determines the percentage of the region affected by disease. A numerical PASI score is derived that evaluates the severity of symptoms in terms of the total body surface area affected. Total PASI score ranges from 0 to 72, with higher scores indicating more severe disease.
Time Frame
Up to 8 weeks after end of FT (up to Week 20)
Title
Percentage of Participants With Psoriasis Exacerbation
Description
Exacerbation was defined as disease worsening either during or after treatment which was more inflammatory in nature compared to baseline and occurred either within pre-existing plaques, at previously uninvolved sites, or as new morphologies of disease.
Time Frame
During study (40 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Moderate to severe plaque psoriasis participants who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA Age at least 18 years For women of childbearing potential and for men whose partner can become pregnant, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study and up to 3 months after the last dose of efalizumab Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care Discontinuation of any systemic psoriasis treatment prior to commencement of the study drug. No washout period is required for these agents prior to starting study and receiving first dose of study drug (efalizumab) Discontinuation of all biologic agents (other than efalizumab) 3 months prior to receiving first dose of study drug (efalizumab) Discontinuation of any investigational drug or treatment 3 months prior to Study Day 0 or as per washout requirements from previous protocol No primary vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug The participant must be willing and able to comply with the protocol requirements for the duration of the study Exclusion Criteria: Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis Participants who have previously been on efalizumab treatment who withdrew due to lack of efficacy or an adverse event. If withdrawal was due to another non-drug reason (vaccination, or infection) then the patient can be included in this study History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection History of opportunistic infections (eg, systemic fungal infections, parasites) Seropositivity for human immunodeficiency virus (HIV). Participants will undergo mandatory testing at screening. Participants who are positive for HIV will be excluded Pregnancy or breast feeding White Blood Cell (WBC) count less than (<) 4*10^9 per liter or greater than (>) 14*10^9 per liter Participants with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count <100*10^9 per liter Seropositivity for hepatitis B or C virus. Participants will undergo testing at screening. Participants who are positive for hepatitis B antigen or hepatitis C antibody will be excluded History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to Study Day 0. Chest X-ray (within 3 months prior to Study Day 0) is required for high-risk participants. Participants with a positive chest X-ray will be excluded Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Participants with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year Any medical condition that, in the judgment of the investigator, would jeopardize the participant's safety following exposure to study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Medical Information
City
Feltham
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
20098509
Citation
Katsambas A, Peris K, Vena G, Freidmann P, Wozel G, Dauden E, Licu D, Placchi M, De La Brassinne M. Assessing the Impact of Efalizumab on Nail, Scalp and Palmoplantar Psoriasis and on Quality of Life: Results from a Multicentre, Open-label, Phase IIIb/IV Trial. Arch Drug Inf. 2009 Dec;2(4):66-70. doi: 10.1111/j.1753-5174.2009.00023.x.
Results Reference
result
PubMed Identifier
20428228
Citation
Lotti T, Chimenti S, Katsambas A, Ortonne JP, Dubertret L, Licu D, Simon J. Efficacy and Safety of Efalizumab in Patients with Moderate-to-Severe Plaque Psoriasis Resistant to Previous Anti-Psoriatic Treatment: Results of a Multicentre, Open-label, Phase IIIb/IV Trial. Arch Drug Inf. 2010 Mar;3(1):9-18. doi: 10.1111/j.1753-5174.2009.00026.x.
Results Reference
result

Learn more about this trial

A Study of Efalizumab in Participants With Moderate to Severe Chronic Psoriasis Who Have Failed, Have a Contraindication to, or Are Intolerant of Other Systemic Therapies

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