Antibody Treatment for Advanced Celiac Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Mayo Clinic
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01893775
First received: May 23, 2013
Last updated: May 13, 2014
Last verified: April 2014
  Purpose

Background:

- Celiac disease is a condition where the immune system attacks the cells of the small intestine. The intestine becomes inflamed and cannot digest food properly. The disease most often causes a reaction to foods that contain gluten. Most people can treat celiac disease with a gluten-free diet. However, some people have digestion problems even on a gluten-free diet. Researchers want to try a new antibody therapy for celiac disease. The treatment may block the immune reaction that causes the disease. They will test this antibody in people who have celiac disease that has not responded to a gluten-free diet.

Objectives:

- To see if antibody therapy is a safe and effective treatment for celiac disease that has not responded to standard treatments.

Eligibility:

- Individuals at least 18 years of age who have been on a gluten-free diet for 6 to 12 months but still have symptoms of celiac disease.

Design:

  • Participants will be screened with a physical exam and medical history. Blood samples will be collected. These samples will help determine if the specific antibody treatment is likely to work.
  • Before the start of the study, participants will have a biopsy of the small intestine.
  • Participants will receive three doses of the study antibody as injections. These doses will be given 3 weeks apart.
  • Treatment will be monitored with blood tests and heart function tests. Participants will also have a second small intestine biopsy within a week after the last dose of the antibody.

Condition Intervention Phase
Celiac Disease
Celiac Sprue
Gluten Enteropathy
Gluten-Sensitive Enteropathy
Biological: Hu-Mik- Beta-1
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of the Humanized Mik-Beta-1 Monoclonal Antibody Directed Toward IL-2/IL-15R Beta (CD122) That Blocks IL-15 Action In Patients With Refractory Celiac Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • safety of Hu MIK Beta 1 in celiac disease pts [ Time Frame: end of week 9 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: June 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Hu-Mik-Beta-1 every 3 weeks
Biological: Hu-Mik- Beta-1
Hu-Mik-Beta-1 every 3 weeks for a total of 3 doses (given on day 1, week 3 and week 6)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA

2.1.1.1 Patients must be greater than or equal to 18-years-old.

2.1.1.2 All patients must have a pathologically confirmed diagnosis of refractory celiac disease(RCD) defined by internationally accepted criteria of persistent and recurrent symptoms(diarrhea, weight loss, and abdominal pain) associated with intestinal damage, characterized by partial to total villous atrophy with intraepithelial lymphocytes defined by > 25 intraepithelial lymphocytes per 100 epithelial cells.

2.1.1.3 Persistence of the above signs and symptoms despite strict adherence to a gluten-free diet for 6-12 months

2.1.1.4 Patients are to have had circulating antibodies to transglutaminase-1 or similar celiac specific serology

2.1.1.5 Patients must have a life expectancy of > 3 months

2.1.1.6 Patients must have a creatinine of less than 2.0 mg/dL or if the patient has an elevated creatinine measured creatinine clearance (Ccr) must be > 60 mL/min/1.73m(2)

2.1.1.7 Patients must have a serum alkaline phosphatase, ALT (SGPT) and AST (SGOT) less than 3x the upper limits of normal (ULN)

2.1.1.8 Patients must have a total bilirubin of less than 2.5 x ULN

2.1.1.9 Women of childbearing potential must have a negative beta HCG pregnancy test at initial screening and within 3 days prior to registration

2.1.1.10 Patients receiving a stable dose (> 4 weeks) of corticosteroid therapy equal to 20 mg of prednisone per day or less are eligible

2.1.1.11 Patients with a history of curatively treated basal cell carcinoma or intraepithelial neoplasia of the uterine surface will be allowed on the study

2.1.1.12 Patients must be able to understand and sign an informed consent

EXCLUSION CRITERIA

2.1.2.1 Patients enrolled in another therapeutic study

2.1.2.2 Patients with a history of venous thrombosis

2.1.2.3 Patients with antibodies to Hu-Mik-Beta-1

2.1.2.4 A contraindication to monoclonal antibody therapy including adverse events related to prior monoclonal antibody therapy. Patients who have received prior antibody therapy will have permanent medical records reviewed by the study investigator.

2.1.2.5 Any uncontrolled or chronic bacterial, mycobacterial or other viral (e.g., herpes virus), fungal, parasitic or protozoal infection

2.1.2.6 History of malignancy (active or within the previous 5 years)

2.1.2.7 Patients with HIV infection (antibody positive) with positive confirmatory molecular tests

2.1.2.8 Patients who have chronic hepatitis B or chronic hepatitis C

2.1.2.9 Pregnant or breastfeeding women. Women who not using an acceptable method of contraception. Acceptability of various methods of contraception will be determined by the investigator. Postmenopausal or surgically sterile women who have documentation of postmenopausal status or surgical sterility availability prior to enrollment.

2.1.2.10 Patients with significant co-morbidities including uncontrolled hypertension (diastolic B/P > 115 mm/Hg), unstable angina, congestive heart failure (> N.Y.H.A. Class II), poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty or myocardial infarction within the last 6 months or uncontrolled atrial or ventricular cardiac arrhythmias.

2.1.2.11 Abnormal screening/baseline tests exceeding the limits outlined below:

  • Total white blood cell count (WBC) < 300/mm(3)
  • Platelet count < 85,000/mm(3)
  • INR greater than or equal to 1.5
  • Serum creatinine level > 1.5 mg/dL
  • Serum alanine transaminase, aspartate transaminase or creatinine kinase > 2 x the upper limits of normal

2.1.2.12 Patients with a history of a psychiatric disorder that may interfere with the understanding and compliance with this protocol, and the required follow-up

2.1.2.13 Exclusion at the discretion of the PI or delegate if participation in the study is deemed too risky (e.g., clinically significant pleural or pericardial effusion or ascites)

2.1.2.14 Inability to give informed consent

  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: NCT01893775

Contacts
Contact: Thomas A Waldmann, M.D. (301) 496-6656 tawald@mail.nih.gov

Locations
United States, Minnesota
Mayo Clinic, Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Carol Van Dyke    507-266-7842    vandyke.carol@mayo.edu   
Contact: Deanna Brogan    (507) 538-1206    brogan.deanna@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Thomas A Waldmann, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01893775     History of Changes
Other Study ID Numbers: 999913148, 13-C-N148
Study First Received: May 23, 2013
Last Updated: May 13, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Anti CD 122
Monoclonal Antibody Therapy
Autoimmune Inflammatory Enteropathy

Additional relevant MeSH terms:
Celiac Disease
Intestinal Diseases
Malabsorption Syndromes
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014