Safety Study of the Monoclonal Antibody Teplizumab (MGA031) in Subjects With Moderate or More Severe Psoriasis
Primary Purpose
Psoriasis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
teplizumab
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis focused on measuring chronic plaque psoriasis, psoriatic arthritis
Eligibility Criteria
Inclusion Criteria:
- Chronic plaque psoriasis that has been present for more than 6 months and involves at least 10% Body Surface Area (BSA).
- Baseline LS-PGA score of moderate or greater severity.
- Weight <= 125 kg (276 lb) and a BSA <= 2.5 m^2.
Exclusion Criteria:
- Clinically significant flare of psoriasis during the 12 weeks before enrollment.
- Guttate, erythrodermic, palmoplantar, or pustular (von Zumbusch) psoriasis
- Orally administered systemic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks before enrollment.
- Prior administration of a biologic agent/monoclonal antibody within 12 weeks before enrollment or 5 half-lives of the agent, whichever is greater.
- Prior otelixizumab, OKT®3, or teplizumab.
- Treatment within the last 30 days with a non-biologic drug or device that has not received regulatory approval for any indication at the time of study entry or are unwilling to forgo experimental treatment other than teplizumab during this study.
- Treatment with live vaccine within 8 weeks before enrollment or during study; vaccination with an antigen or killed organism during the study, within 8 weeks before enrollment, or 8 weeks after dosing.
- Evidence of active infection.
- Positive IgM test for hepatitis A.
- History of or positive test for hepatitis B, C, or D.
- History of or positive test for HIV.
- Are immunocompromised, have had recent or current serious systemic or local infection, clinical or radiological evidence of active tuberculosis, or evidence of latent TB infection.
- History of chronic liver disease, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or epilepsy.
- Current serious or unstable illnesses or allergies.
- Clinically significant laboratory abnormalities.
- Presence of serological reactivity to teplizumab (in subjects previously treated with therapeutic antibodies).
- Clinically significant ECG abnormalities.
Sites / Locations
- University of Michigan Medical Center
- Oregon Health & Science University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
teplizumab
Arm Description
Anti CD-3 monoclonal antibody
Outcomes
Primary Outcome Measures
Adverse Events (AE)
Primary endpoints include safety data such as vital signs, physical examinations, electrocardiograms, AE reports, and laboratory test results.
Secondary Outcome Measures
Number of Participants Improved on Lattice System Physician's Global Assessment (LS-PGA)
The LS-PGA score is determined by estimating the extent of body surface area involved by psoriasis and rating plaque qualities (elevation, erythema, scaling) averaged over the entire body. LS-PGA score is then determined using available software. LS-PGA ranks involvement on an 8 point scale from clear, almost clear, mild, mild to moderate, moderate, moderate to severe, severe, and very severe. Participants who have an improvement of one or more steps in the LS-PGA will be considered to have met the primary criteria for a clinical response.
Number of Participants Improved on the Psoriasis Area and Severity Index (PASI)
The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of plaque scale, erythema, and plaque induration (thickness) in each region, yielding an overall score of 0 for no psoriasis to a maximum of 72 for severe disease.
Physician's Global Assessment (PGA)
The PGA rates the subject's psoriasis relative to baseline as 1 (100% clearing), 2 (excellent: 75% through 99% clearing with striking improvement), 3 (good: 50% through 74% clearing with moderate improvement), 4 (fair: 25% through 49% clearing with slight improvement), 5 (poor: 0% through 24% clearing with little or no change), or 6 (worsening). Involvement of body-surface area, induration, scaling, and erythema are taken into account.
Teplizumab Blood Levels
Full Information
NCT ID
NCT00954915
First Posted
August 4, 2009
Last Updated
February 4, 2022
Sponsor
MacroGenics
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00954915
Brief Title
Safety Study of the Monoclonal Antibody Teplizumab (MGA031) in Subjects With Moderate or More Severe Psoriasis
Official Title
A Phase 2a, Open Label, Multiple-Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Teplizumab in Adults With Moderate or More Severe Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Injection site reaction met protocol-defined stopping criteria.
Study Start Date
December 2009 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics
Collaborators
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether teplizumab is safe when administered subcutaneously (by needle under the skin) in subjects with psoriasis. The study will also evaluate how long teplizumab stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it improves psoriasis.
Detailed Description
This study will test the hypotheses that therapeutic modulation of T-cell function by teplizumab is well tolerated in subjects with moderate or more severe psoriasis, and that this treatment ameliorates the immunopathology of psoriasis. This study will evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) administration for 6 days. Once the SC maximum tolerated dose is identified, this dose will be administered to a cohort of subject by intravenous for comparison of PK and PD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
chronic plaque psoriasis, psoriatic arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
teplizumab
Arm Type
Experimental
Arm Description
Anti CD-3 monoclonal antibody
Intervention Type
Biological
Intervention Name(s)
teplizumab
Other Intervention Name(s)
MGA031
Intervention Description
Cohorts 1-5: escalating doses of subcutaneously administered teplizumab; cohort 6: intravenous administration of maximum tolerated subcutaneous dose.
Primary Outcome Measure Information:
Title
Adverse Events (AE)
Description
Primary endpoints include safety data such as vital signs, physical examinations, electrocardiograms, AE reports, and laboratory test results.
Time Frame
Day 0 through Day 84
Secondary Outcome Measure Information:
Title
Number of Participants Improved on Lattice System Physician's Global Assessment (LS-PGA)
Description
The LS-PGA score is determined by estimating the extent of body surface area involved by psoriasis and rating plaque qualities (elevation, erythema, scaling) averaged over the entire body. LS-PGA score is then determined using available software. LS-PGA ranks involvement on an 8 point scale from clear, almost clear, mild, mild to moderate, moderate, moderate to severe, severe, and very severe. Participants who have an improvement of one or more steps in the LS-PGA will be considered to have met the primary criteria for a clinical response.
Time Frame
Day 0, 14, 28, 63 and 84
Title
Number of Participants Improved on the Psoriasis Area and Severity Index (PASI)
Description
The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of plaque scale, erythema, and plaque induration (thickness) in each region, yielding an overall score of 0 for no psoriasis to a maximum of 72 for severe disease.
Time Frame
Day 0, 14, 28, 63 and 84
Title
Physician's Global Assessment (PGA)
Description
The PGA rates the subject's psoriasis relative to baseline as 1 (100% clearing), 2 (excellent: 75% through 99% clearing with striking improvement), 3 (good: 50% through 74% clearing with moderate improvement), 4 (fair: 25% through 49% clearing with slight improvement), 5 (poor: 0% through 24% clearing with little or no change), or 6 (worsening). Involvement of body-surface area, induration, scaling, and erythema are taken into account.
Time Frame
Day 0, 14, 28, 63 and 84
Title
Teplizumab Blood Levels
Time Frame
Day 0 through Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic plaque psoriasis that has been present for more than 6 months and involves at least 10% Body Surface Area (BSA).
Baseline LS-PGA score of moderate or greater severity.
Weight <= 125 kg (276 lb) and a BSA <= 2.5 m^2.
Exclusion Criteria:
Clinically significant flare of psoriasis during the 12 weeks before enrollment.
Guttate, erythrodermic, palmoplantar, or pustular (von Zumbusch) psoriasis
Orally administered systemic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks before enrollment.
Prior administration of a biologic agent/monoclonal antibody within 12 weeks before enrollment or 5 half-lives of the agent, whichever is greater.
Prior otelixizumab, OKT®3, or teplizumab.
Treatment within the last 30 days with a non-biologic drug or device that has not received regulatory approval for any indication at the time of study entry or are unwilling to forgo experimental treatment other than teplizumab during this study.
Treatment with live vaccine within 8 weeks before enrollment or during study; vaccination with an antigen or killed organism during the study, within 8 weeks before enrollment, or 8 weeks after dosing.
Evidence of active infection.
Positive IgM test for hepatitis A.
History of or positive test for hepatitis B, C, or D.
History of or positive test for HIV.
Are immunocompromised, have had recent or current serious systemic or local infection, clinical or radiological evidence of active tuberculosis, or evidence of latent TB infection.
History of chronic liver disease, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or epilepsy.
Current serious or unstable illnesses or allergies.
Clinically significant laboratory abnormalities.
Presence of serological reactivity to teplizumab (in subjects previously treated with therapeutic antibodies).
Clinically significant ECG abnormalities.
Facility Information:
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety Study of the Monoclonal Antibody Teplizumab (MGA031) in Subjects With Moderate or More Severe Psoriasis
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