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

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

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.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: OKT3

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah University Hospital, Liver Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who have completed the informed consent process culminating with written informed consent by the subject.
2. Men and women age 18 to 75 years (inclusive)
3. Patients with biopsy proven NASH within the last 3 years
4. 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.
5. HBA1C between 5.5 and 14%.

Exclusion Criteria:

1. Subjects who have undergone surgery within the last 3 months.
2. Subjects who have had a prior gastrointestinal surgery.
3. Subjects with a clinically significant infectious, immune mediated or malignant disease
4. Subjects who are receiving an elemental diet or parenteral nutrition.
5. Subjects who have been treated with any type of immune modulatory drug including steroids or NSAID within the last 4 weeks
6. 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.
7. Subjects with a history of coagulopathy.
8. 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.
9. 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.
10. Subjects who are HIV-positive.
11. Subjects who are HBV-positive
12. Subjects who are HCV-positive.
13. Subjects with active CMV
14. Subjects with anemia (Hb <10.5 gm/dl).
15. Subjects with thrombocytopenia (platelets <100K/µl).
16. Subjects with lymphopenia (absolute lymphocyte count <0.7).
17. Subjects with IgG anti-cardiolipin antibody >16 IU.
18. Prior exposure to anti-CD3 MAb.
19. Known sensitivity to any ingredients in the study drug
20. Any know autoimmune disease except for the studied disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: OKT3; 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.; Other Names: Omeprazole
ACTIVE_COMPARATOR: OKT3 - 0.2	Drug: OKT3; 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.; Other Names: Omeprazole
ACTIVE_COMPARATOR: OKT3 - 1	Drug: OKT3; 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.; Other Names: Omeprazole
ACTIVE_COMPARATOR: OKT3 - 5	Drug: OKT3; 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.; Other Names: Omeprazole

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: NasVax Ltd

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: May 23, 2010
• First Submitted That Met QC Criteria: September 16, 2010
• First Posted (ESTIMATE): September 20, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 23, 2011
• Last Update Submitted That Met QC Criteria: June 22, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Liver Diseases; Insulin Resistance; Hyperinsulinism; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: OKT3-NASH-HMO-CTIL