Oral OKT3 for the Treatment of Active Ulcerative Colitis

NCT01287195 | Completed Phase 1 Results DMC

• 1 other identifier: 2009P001448
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Adverse Events

  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.

  From baseline to Week 10

• Number of Participants With Anti-Drug Antibodies

  Serum samples were obtained to measure anti-drug antibodies during the study.

  From baseline to Week 10

• Percentage of Biomarker-positive Immune Cells

  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.

  Baseline, Week 5

• T Cell Proliferation of PBMCs in Cell Culture

  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.

  Baseline, Weeks 1, 3 and 5

• Cytokine Production by PBMCs in Cell Culture

  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.

  Baseline, Weeks 1, 3 and 5

Secondary Outcomes (3)

• Mayo Score

  Baseline, Week 5

• Simple Clinical Colitis Activity Index (SCCAI) Score

  Baseline, Week 5

• Score in Histologic Evaluation of Flexible Sigmoidoscopy

  Baseline, Week 5

Study Arms (1)

Oral OKT3

EXPERIMENTAL

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

Drug: Oral OKT3; Drug: Omeprazole

Interventions

Oral OKT3 DRUG

1 mg or 2 mg Oral OKT3 will be given orally to participants once daily for 30 days

Also known as: Muromonab CD3, OKT3, anti-CD3

Oral OKT3

Omeprazole DRUG

20 mg Omeprazole will be given orally to participants once daily for 30 days

Also known as: Prilosec

Oral OKT3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (5)

• Ilan Y, Zigmond E, Lalazar G, Dembinsky A, Ben Ya'acov A, Hemed N, Kasis I, Axelrod E, Zolotarov L, Klein A, El Haj M, Gandhi R, Baecher-Allan C, Wu H, Murugaiyan G, Kivisakk P, Farez MF, Quintana FJ, Khoury SJ, Weiner HL. Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells. J Clin Immunol. 2010 Jan;30(1):167-77. doi: 10.1007/s10875-009-9323-7. Epub 2009 Sep 16.

  PMID: 19756989 BACKGROUND

• Wu HY, Maron R, Tukpah AM, Weiner HL. Mucosal anti-CD3 monoclonal antibody attenuates collagen-induced arthritis that is associated with induction of LAP+ regulatory T cells and is enhanced by administration of an emulsome-based Th2-skewing adjuvant. J Immunol. 2010 Sep 15;185(6):3401-7. doi: 10.4049/jimmunol.1000836. Epub 2010 Aug 18.

  PMID: 20720210 BACKGROUND

• Wu HY, Center EM, Tsokos GC, Weiner HL. Suppression of murine SLE by oral anti-CD3: inducible CD4+CD25-LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells. Lupus. 2009 Jun;18(7):586-96. doi: 10.1177/0961203308100511.

  PMID: 19433458 BACKGROUND

• Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL. Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes. 2007 Aug;56(8):2103-9. doi: 10.2337/db06-1632. Epub 2007 Apr 24.

  PMID: 17456848 BACKGROUND

• Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, Wu H, Chen ML, Gandhi R, Miller A, Maron R, Weiner HL. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells. Nat Med. 2006 Jun;12(6):627-35. doi: 10.1038/nm1408. Epub 2006 May 21.

  PMID: 16715091 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Muromonab-CD3; Omeprazole

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Scott B. Snapper, M.D., Ph.D.
• Organization: Brigham and Women's Hospital

ssnapper@partners.org

617-919-4973

Study Officials

• Scott Snapper, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Inflammatory Bowel Disease Research

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 1, 2011
• Study Start: April 7, 2011
• Primary Completion: May 2, 2013
• Study Completion: May 2, 2013
• Last Updated: February 11, 2019
• Results First Posted: June 14, 2017

Record last verified: 2019-01

Locations

US (1)