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

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

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.

Study Overview

• Status: Terminated
• Conditions: Psoriasis
• Intervention / Treatment: Biological: teplizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: MGA031

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MacroGenics
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 4, 2009
• First Submitted That Met QC Criteria: August 6, 2009
• First Posted (Estimate): August 7, 2009

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: psoriatic arthritis; chronic plaque psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: CP-MGA031-04