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

Purpose

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.

Condition	Intervention	Phase
Psoriasis	Biological: teplizumab	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: psoriatic arthritis

MedlinePlus related topics: Psoriasis

U.S. FDA Resources

Further study details as provided by MacroGenics:

Primary Outcome Measures:

Adverse Events (AE) [ Time Frame: Day 0 through Day 84 ] [ Designated as safety issue: No ]
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) [ Time Frame: Day 0, 14, 28, 63 and 84 ] [ Designated as safety issue: No ]
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) [ Time Frame: Day 0, 14, 28, 63 and 84 ] [ Designated as safety issue: No ]
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) [ Time Frame: Day 0, 14, 28, 63 and 84 ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 0 through Day 84 ] [ Designated as safety issue: No ]

Enrollment:	1
Study Start Date:	December 2009
Study Completion Date:	July 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: teplizumab Anti CD-3 monoclonal antibody	Biological: teplizumab Cohorts 1-5: escalating doses of subcutaneously administered teplizumab; cohort 6: intravenous administration of maximum tolerated subcutaneous dose. Other Name: MGA031

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00954915

Locations

United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239

Sponsors and Collaborators

MacroGenics

Eli Lilly and Company

Investigators

Study Chair:

Stanford J Stewart, MD

MacroGenics

More Information

No publications provided

Responsible Party:	MacroGenics
ClinicalTrials.gov Identifier:	NCT00954915 History of Changes
Other Study ID Numbers:	CP-MGA031-04
Study First Received:	August 4, 2009
Results First Received:	March 27, 2012
Last Updated:	August 20, 2012
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by MacroGenics:

chronic plaque psoriasis
psoriatic arthritis

Additional relevant MeSH terms:

Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013