Antibody Treatment for Advanced Celiac Disease

NCT01893775 | Completed Phase 1 FDA Drug

• 2 other identifiers: 99991314813-C-N148
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Celiac Disease; Celiac Sprue; Gluten Enteropathy; Gluten-Sensitive Enteropathy

Keywords

Anti CD 122; Monoclonal Antibody Therapy; Autoimmune Inflammatory Enteropathy

Outcome Measures

Primary Outcomes (1)

• safety of Hu MIK Beta 1 in celiac disease pts

  Events will be tabulated and reported by grade with evaluationalso of supportive medications and surrogate markers of absorptionsuch as body mass index, albumin and hemoglobin.

  end of week 9

Study Arms (1)

1

EXPERIMENTAL

Hu-Mik-Beta-1 every 3 weeks

Biological: Hu-Mik- Beta-1

Interventions

Hu-Mik- Beta-1 BIOLOGICAL

Hu-Mik-Beta-1 every 3 weeks for a total of 3 doses (given on day 1, week 3 and week 6)

1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be greater than or equal to 18-years-old.
• 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.
• Persistence of the above signs and symptoms despite strict adherence to a gluten-free diet for 6-12 months
• Patients are to have had circulating antibodies to transglutaminase-1 or similar celiac specific serology
• Patients must have a life expectancy of \> 3 months
• 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)
• Patients must have a serum alkaline phosphatase, ALT (SGPT) and AST (SGOT) less than 3x the upper limits of normal (ULN)
• Patients must have a total bilirubin of less than 2.5 x ULN
• Women of childbearing potential must have a negative beta HCG pregnancy test at initial screening and within 3 days prior to registration
• Patients receiving a stable dose (\> 4 weeks) of corticosteroid therapy equal to 20 mg of prednisone per day or less are eligible
• Patients with a history of curatively treated basal cell carcinoma or intraepithelial neoplasia of the uterine surface will be allowed on the study
• Patients must be able to understand and sign an informed consent

You may not qualify if:

• Patients enrolled in another therapeutic study
• Patients with a history of venous thrombosis
• Patients with antibodies to Hu-Mik-Beta-1
• 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.
• Any uncontrolled or chronic bacterial, mycobacterial or other viral (e.g., herpes virus), fungal, parasitic or protozoal infection
• History of malignancy (active or within the previous 5 years)
• Patients with HIV infection (antibody positive) with positive confirmatory molecular tests
• Patients who have chronic hepatitis B or chronic hepatitis C
• 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.
• 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.
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Mayo Clinic: collaborator

Study Sites (1)

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (3)

• Trier JS. Celiac sprue. N Engl J Med. 1991 Dec 12;325(24):1709-19. doi: 10.1056/NEJM199112123252406. No abstract available.

  PMID: 1944472 BACKGROUND

• Ryan BM, Kelleher D. Refractory celiac disease. Gastroenterology. 2000 Jul;119(1):243-51. doi: 10.1053/gast.2000.8530.

  PMID: 10889175 BACKGROUND

• Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B, Macintyre E, Cerf-Bensussan N, Brousse N. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet. 2000 Jul 15;356(9225):203-8. doi: 10.1016/s0140-6736(00)02481-8.

  PMID: 10963198 BACKGROUND

MeSH Terms

Conditions

Celiac Disease

Interventions

Hu-Mik-beta-1 monoclonal antibody

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Thomas A Waldmann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: July 9, 2013
• Study Start: June 12, 2013
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: January 18, 2020

Record last verified: 2019-12-20

Locations

US (1)