Safety Study of the Monoclonal Antibody Teplizumab (MGA031) in Subjects With Moderate or More Severe Psoriasis

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: teplizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: teplizumab<br>Anti CD-3 monoclonal antibody | Biological: teplizumab<br>* Cohorts 1-5: escalating doses of subcutaneously administered teplizumab; cohort 6: intravenous administration of maximum tolerated subcutaneous dose.<br>* Other names: MGA031;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) | Primary endpoints include safety data such as vital signs, physical examinations, electrocardiograms, AE reports, and laboratory test results. | Day 0 through Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 0, 14, 28, 63 and 84 | 
| 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. | Day 0, 14, 28, 63 and 84 | 
| 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. | Day 0, 14, 28, 63 and 84 | 
| Teplizumab Blood Levels |  | Day 0 through Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic plaque psoriasis, psoriatic arthritis