Clinical trial NCT00954915: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Psoriasis
Keywords: chronic plaque psoriasis
psoriatic arthritis
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2009-08-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse Events (AE)
timeFrame: Day 0 through Day 84
Secondary outcomes:
measure: Number of Participants Improved on Lattice System Physician's Global Assessment (LS-PGA)
timeFrame: Day 0, 14, 28, 63 and 84
measure: Number of Participants Improved on the Psoriasis Area and Severity Index (PASI)
timeFrame: Day 0, 14, 28, 63 and 84
measure: Physician's Global Assessment (PGA)
timeFrame: Day 0, 14, 28, 63 and 84
measure: Teplizumab Blood Levels
timeFrame: Day 0 through Day 84
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
References: