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
Trial status: Open for Enrollment
Why is this study being done?
The purpose of this study is to assess the administration of a monoclonal antibody (HU-Mik-β1) for the treatment of Refractory Celiac Disease. Currently there are no established or effective treatments for RCD beyond supportive measures and immune suppressive-like steroids. The drug targets the effects of a signal (IL-15) in the body that is believed to cause much of the damage in the intestine from refractory celiac disease. It is hoped that this drug will lessen the damage in your intestine and/or lessen the severity of the RCD.
HU-Mik-β1 is experimental and isn't approved by the U.S. Food and Drug Administration (FDA). However, the FDA has allowed the use of this drug in this research study.
Who is eligible to participate?
- At least 18 years old
- Persistence of diarrhea, weight loss, abdominal pain symptoms despite strict adherence to a gluten-free diet for 6-12 months
- Must have circulating antibodies to transglutaminase-1
- Live expectancy of more than 3 months
- 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/1.73m2
- Serum alkaline phosphatase, ALT (SGPT) and AST (SGOT) less than 3x the upper limits of normal (ULN)
- 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 = 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
- 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
- regnant 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.
- Total white blood cell count (WBC) <300/mm3
- Platelet count <85,000/mm3
- 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
- Patients with a history of a psychiatric disorder that may interfere with the understanding and compliance with this protocol, and the required follow-up
- 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)
- Inability to give informed consent