Oral OKT3 for the Treatment of Active Ulcerative Colitis

Phase 1

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Oral OKT3
Drug: Omeprazole

Registration Number: NCT01287195

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: This study will assess the safety and efficacy of orally delivered short-term OKT3 in participants with active ulcerative colitis.

Detailed Description: Ulcerative colitis (UC) is a chronic disease of unknown etiology characterized by infiltration of inflammatory cells into the intestinal tract. OKT3 is an approved drug for intravenous use in the treatment of solid-organ transplantation. However, intravenous dosing has been limited by significant toxicities. Data from animal models suggest that antibody recognizing the T3 antigen complex Cluster of Differentiation 3 (anti-CD3) administered via the oral route is effective at treating a variety of autoimmune diseases. No side effects were observed in a recent phase I study of healthy participants receiving oral anti-CD3 monoclonal antibody (mAb).

The objectives of the current study are to assess the safety, immunologic effects and efficacy of short-term oral administration of OKT3 in participants with active ulcerative colitis. OKT3 will be delivered orally as a 1 milligram (mg) or 2 mg dose with Omeprazole 20 mg daily for 30 consecutive days in an open-label pilot trial. Thirty two participants will be screened for a targeted completion of 16 enrolled participants. The participants will be evaluated at baseline, day 1, day 2, week 1, week 3, as well as after completion of therapy at week 5 and 10 after the initiation of treatment. Lab tests will be performed at screening, baseline, day 2, week 1, week 3, week 5 and week 10. Clinical data will be collected at all study visits and via diary entries throughout the study period. A flexible sigmoidoscopy will be done at baseline and at week 5. Stool studies will be performed at screening to rule out infection.

To be eligible for this study, participants must be between the ages of 18 and 65 years and have a history of moderately to severely active UC as defined by a Mayo score of 6 to 12. They may not be taking concurrent biologic or immunomodulator therapy for UC.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral OKT3	Oral OKT3	Participants with ulcerative colitis will receive Oral OKT3 given with Omeprazole once daily for 30 days.
Oral OKT3	Omeprazole	Participants with ulcerative colitis will receive Oral OKT3 given with Omeprazole once daily for 30 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	From baseline to Week 10	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Biomarker-positive Immune Cells	Baseline, Week 5	Peripheral blood mononuclear cells were (PBMCs) were isolated from blood samples taken from each participant at baseline and Week 5. PBMCs were stained with a panel of fluorochrome-conjugated antibodies against multiple surface and intracellular biomarkers, including Cluster of Differentiation (CD) 3, CD4, CD8, Forkhead box P3 protein (FOXP3) and latency-associated peptide (LAP). The percentage of T cells positive for each of these biomarkers was determined by fluorescence activated cell sorting (FACS) and the mean percentage of positive T cells for each biomarker for all analyzed participants is reported.
Number of Participants With Anti-Drug Antibodies	From baseline to Week 10	Serum samples were obtained to measure anti-drug antibodies during the study.
T Cell Proliferation of PBMCs in Cell Culture	Baseline, Weeks 1, 3 and 5	PBMCs isolated from whole blood obtained from participants at baseline, Weeks 1, 3, and 5 were assessed for proliferation in cell culture using a radioactive thymidine incorporation assay. A higher number indicates a higher level of proliferation.
Cytokine Production by PBMCs in Cell Culture	Baseline, Weeks 1, 3 and 5	Cytokine production was assessed in cell cultures of PBMCs obtained from participants at baseline, Weeks 1, 3 and 5. The following cytokines were detected and are reported here: interferon gamma (IFN-gamma), interleukin (IL)-17A, IL-6, IL-1 beta, tumor necrosis factor (TNF) and IL-10.

Secondary Outcome Measures

Name	Time	Method
Mayo Score	Baseline, Week 5	The Mayo Score is determined by the investigator by assigning a score to the following four assessments: stool frequency, rectal bleeding, physician's global assessment and endoscopy. Total range for Mayo score is 0-12 with a higher score indicating a worse outcome.
Simple Clinical Colitis Activity Index (SCCAI) Score	Baseline, Week 5	SCCAI is a symptom based questionnaire addressing five assessments, including bowel frequency day, bowel frequency night, urgency of defecation, blood in stool and general well-being. Score ranges from 0-15 with one additional point added for each manifestation of extracolonic features. A higher score indicates a worse outcome.
Score in Histologic Evaluation of Flexible Sigmoidoscopy	Baseline, Week 5	Mucosal biopsies were obtained from the most inflamed area seen during flexible sigmoidoscopy and blindly scored by a single pathologist with scores ranging 0-3 with a higher score indicating a worse outcome.