Oral OKT3 for the Treatment of Active Ulcerative Colitis

Mass General Brigham

Status and phase

Completed

Phase 2

Phase 1

Conditions

Ulcerative Colitis

Treatments

Drug: Omeprazole

Drug: Oral OKT3

Study type

Interventional

Funder types

Other

Identifiers

NCT01287195

2009P001448

Details and patient eligibility

About

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

Full 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.

Enrollment

6 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

1.1 Inclusion Criteria

Ability to provide informed consent
Age between 18 and 65 years
Confirmed diagnosis of UC for at least 3 months with the extent defined within the previous year
Moderate to severe UC as defined by a Mayo score of 6-12
Concomitant medications: Can be on 5-amino salicylate (5-ASA) medications and stable doses (same dose > 4 weeks) of oral steroids
Concomitant medications cannot include Infliximab, Adalimumab, Certolizumab or Natalizumab for 4 weeks; rectal steroids, 6-mercaptopurine (6-MP), Azathioprine, Tacrolimus, Methotrexate, Thalidomide, Cellcept for 4 weeks; Theophylline, sulfonylureas, non-steroidal anti-inflammatory drug (NSAIDs) or aspirin for 10 days
Negative serum pregnancy test within 2 weeks prior to receiving the first dose of study drug in female participants of child-bearing potential
Female participants of child-bearing potential must be willing to use birth control during the study and for 4 weeks following the last dose of study drug.

1.2 Exclusion Criteria

Crohn's disease or indeterminate colitis
Mayo score of <6 (mild UC)
Hospitalized or exhibiting signs of toxicity (abdominal distension, severe abdominal tenderness, fever, nausea, vomiting, or tachycardia)
A history of colorectal cancer or colorectal dysplasia
Pregnant or breastfeeding females or females wishing to become pregnant within the next 6 months or unwilling to use birth control
Serum creatinine ≥ 2.0 milligrams per deciliter (mg/dL)
Alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or direct bilirubin >1.5x normal: elevated indirect bilirubin related to likely Gilbert's disease permissible
Use of any of the following medications: Azathioprine, 6-MP, Methotrexate, Mycophenolate Mofetil, Tacrolimus, Cyclosporine, Thalidomide, Adalimumab, Infliximab, Certolizumab, Natalizumab, rectal steroids. Theophylline, sulfonylureas, NSAIDs or aspirin within 10 days of study enrollment
Psychiatric illness or substance abuse that would interfere with ability to comply with protocol requirements or give informed consent
Surgery within the last 3 months
Prior gastrointestinal surgery
Clinically significant infectious, immune mediated or malignant disease
Receiving an elemental diet or parenteral nutrition
History of coagulopathy
Human immunodeficiency virus (HIV) positive
Hepatitis B surface antigen (HBsAg) positive
Active cytomegalovirus (CMV)
Anemia: hemoglobin (Hb) < 8 grams/deciliter (g/dL). If the subject has known significant cardiac disease, subjects with Hb < 10.5 g/dL will be excluded.
Thrombocytopenia (platelets < 100,000 per microliter [100K/mcL])
Lymphopenia (absolute lymphocyte count <0.7)
Immunoglobulin G (IgG) anti-cardiolipin antibody positive >16 International Units (IU)
Prior exposure to OKT3
Positive quantiferon gold, tuberculosis (TB) spot test, or purified protein derivative (PPD) test
Known sensitivity to any ingredients in the study drug
Anti-mouse antibody titer >1:1000
Any known autoimmune disease except for ulcerative colitis
Allergy or hypersensitivity to Omeprazole
Participated in another clinical trial within 30 days of screening for this trial