Safety and Efficacy of Oral Administration of Anti-CD3 Monoclonal Antibody (mAb)in Patients With the Metabolic Syndrome

Study Overview
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Brief Summary
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This clinical study is designed to evaluate the safety and immune modulatory effects of oral administration of the study drug anti-CD3 monoclonal antibody (MAb) to subjects with the metabolic syndrome.

Detailed Description
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PHASE IIa STUDY PROTOCOL A Single-blinded Placebo-controlled Clinical Trial.

Official Title
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Safety and Efficacy of Oral Administration of Anti-CD3 Monoclonal Antibody in Patients With the Metabolic Syndrome PHASE IIa A Single-blinded Placebo-controlled Clinical Trial

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: OKT3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have completed the informed consent process culminating with written informed consent by the subject. Men and women age 18 to 75 years (inclusive) Patients with biopsy proven NASH within the last 3 years Altered glucose metabolism, including diabetes (non treated, or treated with up to 2 drugs (not including insulin) without any change in medication for at least 2 months prior to enrollment), impaired fasting glucose or impaired glucose tolerance. HBA1C between 5.5 and 14%. Exclusion Criteria: Subjects who have undergone surgery within the last 3 months. Subjects who have had a prior gastrointestinal surgery. Subjects with a clinically significant infectious, immune mediated or malignant disease Subjects who are receiving an elemental diet or parenteral nutrition. Subjects who have been treated with any type of immune modulatory drug including steroids or NSAID within the last 4 weeks Subjects who have received either methotrexate or cyclosporine or anti TNF-β (infliximab, Remicade), anti-integrin (namixilab) or who have participated in any other clinical trial within the last 3 months. Subjects with a history of coagulopathy. Women with childbearing potential unless surgically sterile or using adequate contraception (either IUD, oral or Depo-provera contraceptive, or barrier plus spermicide); pregnant or breastfeeding mothers. Subjects, who will be unavailable for the duration of the trial, are unlikely to be compliant with the protocol, or who are felt to be unsuitable by the investigator for any other reason. Subjects who are HIV-positive. Subjects who are HBV-positive Subjects who are HCV-positive. Subjects with active CMV Subjects with anemia (Hb <10.5 gm/dl). Subjects with thrombocytopenia (platelets <100K/µl). Subjects with lymphopenia (absolute lymphocyte count <0.7). Subjects with IgG anti-cardiolipin antibody >16 IU. Prior exposure to anti-CD3 MAb. Known sensitivity to any ingredients in the study drug Any know autoimmune disease except for the studied disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: OKT3<br>* Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 patients will be treated at each dosage level, and up to additional 9 patients will receive placebo.<br>* Other names: Omeprazole;|
| Active Comparator: OKT3 - 0.2<br> | Drug: OKT3<br>* Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 patients will be treated at each dosage level, and up to additional 9 patients will receive placebo.<br>* Other names: Omeprazole;|
| Active Comparator: OKT3 - 1<br> | Drug: OKT3<br>* Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 patients will be treated at each dosage level, and up to additional 9 patients will receive placebo.<br>* Other names: Omeprazole;|
| Active Comparator: OKT3 - 5<br> | Drug: OKT3<br>* Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 patients will be treated at each dosage level, and up to additional 9 patients will receive placebo.<br>* Other names: Omeprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This clinical study is designed to evaluate the safety and the immune-modulatory effects of oral administration of the study drug anti-CD3 MAb to subjects with the metabolic syndrome. |  | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This clinical study also will include evaluations for markers of efficacy, as described below. |  | 60 days |