Oral OKT3 for the Treatment of Active Ulcerative Colitis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Scott B. Snapper, M.D., Ph.D., Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01287195
First received: January 28, 2011
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Ulcerative Colitis
Drug: Oral OKT3
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Oral Anti-CD3 for the Treatment of Active Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Oral OKT3 for the treatment of active ulcerative colitis. [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
    adverse drug reaction

  • Oral OKT3 for the Treatment of Active Ulcerative Colitis [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    immunologic assays


Secondary Outcome Measures:
  • Oral OKT3 for the Treatment of Active Ulcerative Colitis [ Time Frame: 5 weeks, 10 weeks ] [ Designated as safety issue: No ]
    Improvement in Mayo Score, Simple colitis activity index

  • Oral OKT3 for the Treatment of Active Ulcerative Colitis [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
    Improvement in histologic evaluation at flexible sigmoidoscopy


Estimated Enrollment: 16
Study Start Date: February 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral OKT3
Subjects will receive 1 mg or 2 mg OKT3 daily for 30 days given with Omeprazole 20 mg daily.
Drug: Oral OKT3
1 mg or 2 mg Oral OKT3 will be given orally to patients for 30 days with Omeprazole 20 mg daily.
Other Names:
  • Muromonab CD3
  • OKT3
  • anti-CD3

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 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 subjects receiving oral anti-CD3 mAb.

The objectives of the current study are to assess the safety, immunologic effects and efficacy of short-term oral administration of OKT3 in patients with active ulcerative colitis . OKT3 will be delivered orally as a 1 mg or 2 mg dose with Omeprazole 20 mg daily for 30 consecutive days in an open-label pilot trial. Thirty two subjects will be screened for a targeted completion of 16 enrolled patients. The subjects 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, subjects 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-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-MP, Azathioprine, Tacrolimus, Methotrexate, Thalidomide, Cellcept for 4 weeks; Theophylline, sulfonylureas, NSAIDs or aspirin for 10 days.
  • Negative serum pregnancy test within 2 weeks prior to receiving the first dose of study drug in female patients of child-bearing potential.
  • Female patients 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)
  • Patients who are 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 mg/dL
  • Alkaline phosphatase, AST, ALT, or direct bilirubin >1.5x normal. Elevated indirect bilirubin related to likely Gilbert's disease is permissible.
  • Use of any of the following medications: Azathioprine, 6-mercaptopurine, 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
  • 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 with a history of coagulopathy
  • Subjects who are HIV positive
  • Subjects who are HBsAg positive
  • Subjects with active CMV
  • Subjects with anemia (Hb < 8 gm/dl). If the patient has known significant cardiac disease, patients with Hb < 10.5 will be excluded.
  • 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 OKT3
  • Subjects with positive quanteferon gold, TB spot test, or PPD
  • 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
  • Subjects who have participated in another clinical trial within 30 days of screening for this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287195

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Scott Snapper, MD, PhD Brigham and Women's Hospital
  More Information

Publications:
Responsible Party: Scott B. Snapper, M.D., Ph.D., Director, Inflammatory Bowel Disease Research, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01287195     History of Changes
Other Study ID Numbers: 2009P001448
Study First Received: January 28, 2011
Last Updated: May 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:
Ulcerative Colitis
Inflammatory Bowel Disease

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Muromonab-CD3
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 01, 2014