Oral OKT3 in Combination With Beta-D-Glucosylceramide

Study Overview
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Brief Summary
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This clinical study is designed to evaluate the safety of oral administration of the study drug anti CD3 (OKT3) in combination with β-D glucosylceramide [GC] .

Detailed Description
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Anti CD3 (OKT3): Is an approved drug for intravenous use in the treatment of solid organ transplantation. Preliminary data suggest that the oral administration of OKT3 in low dosages can exert an immune modulatory effect via activation of regulatory T lymphocytes. β-D glucosylceramide [GC]: Is approved for oral administration and is currently being tested in three clinical trials. Recent data suggested that it can serve as an immunological adjuvant in various clinical settings and to augment the immune response via activation of regulatory T cells. This clinical trial has been designed to assess the safety of oral administration of OKT3 with and without co-administration of GC in healthy subjects. The use of two potential activators of regulatory T cells, may exert an additive effect, augmenting the systemic immune modulatory effect.

Official Title
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Administration of Anti-CD3 (OKT3) in Combination With Beta-D-Glucosylceramide

Conditions
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Healthy

Intervention / Treatment
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* Drug: OKT3
* Drug: OKT3, GC
* Drug: OKT3
* Drug: OKT3, GC
* Drug: OKT3
* Drug: GC


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 > 18 years of age. Exclusion Criteria: Subjects who have undergone surgery within the last 3 months. Subjects who have had a prior colostomy, ileostomy, or colectomy with ileorectal anastamosis. Subjects presenting with, or who have a history of, persistent intestinal obstruction, bowel perforation, uncontrolled bleeding or abdominal abscess or infection, toxic megacolon. 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 time of immune modulatory drug including steroids or NSAID within the last 4 weeks. Subjects who have received either methotrexate or cyclosporine or anti TNF alpha (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 likely to be non¬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 HBsAg positive Subjects who are HCV positive Subjects with active CMV Subjects who demonstrate a positive PPD Subjects with anemia (Hb <10.5 gm/dl) Subjects with thrombocytopenia (platelets <100K/microliter) Subjects with lymphopenia (absolute lymphocyte count <0.7) Subjects with IgG anti-cardiolipin antibody >16 IU Prior exposure to OKT3 Known sensitivity to any ingredients in the study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B<br>Low dose OKT3 with GC | Drug: OKT3, GC<br>* 0.2 mg OKT3 and 7.5 mg GC, PO (in the mouth) on day 1 through 5<br>* Other names: GC, glucosylceramide, beta glucosylceramide;|
| Experimental: C<br>Mid dose OKT3 | Drug: OKT3<br>* 1 mg OKT3, PO (in the mouth) on day 1 through 5<br>* Other names: OKT3, antiCD3;|
| Experimental: D<br>Mid OKT3 dose with GC | Drug: OKT3, GC<br>* 1 mg OKT3 and 7.5 mg GC, PO (in the mouth) on day 1 through 5<br>* Other names: GC, glucosylceramide, beta glucosylceramide;|
| Experimental: E<br>High dose OKT3 | Drug: OKT3<br>* 5 mg OKT3, PO (in the mouth) on day 1 through 5<br>* Other names: GC, glucosylceramide, beta-glucosylceramide;|
| Experimental: F<br>GC only | Drug: GC<br>* 7.5 mg GC, PO (in the mouth) on day 1 through 5<br>* Other names: GC, glucosylceramide, beta glucosylceramide;|
| Experimental: A<br>Low dose OKT3 | Drug: OKT3<br>* 0.2 mg OKT3, PO (in the mouth) on day 1 through 5.<br>* Other names: OKT3, Monoclonal anti CD3.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the safety of oral administration of OKT3 with and without GC in healthy volunteers by monitoring the subjects for adverse events and by interpreting the results of the various laboratory tests and the subjects' diaries. |  | January-April | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of 5 consecutive doses of oral OKT3 with and with out GC and the dose escalation effect in healthy volunteers. |  | January-April | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OKT3, beta-glucosylceramide, oral tolerance, anti-CD3, Safety assessment and healthy volunteers