A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients with Type II Refractory Celiac Disease, an In Situ Small Bowel T Cell Lymphoma

Phase 2

Completed

Conditions: chronic bowel disease
native thrush
10017969

Registration Number: NL-OMON45834

Lead Sponsor: Celimmune LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. Adult males or females 18 years of age or older.
2. Demonstrated willingness to participate in the study as documented by signed informed consent.
3. Females of non-childbearing potential defined as postmenopausal (>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level >40 IU/L at Screening); or permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, oophorectomy); or otherwise incapable of pregnancy
OR
Females of child bearing potential (FOCBP) or males who agree to practice two highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) from Screening through the end of study participation (Visit 9, Week 16/Day 112).
4. Prior confirmed diagnosis of RCD-II defined by the following criteria: celiac disease confirmed by histology, endoscopy or serology; with persistent and recurrent symptoms (e.g., diarrhea, weight loss, abdominal pain); with abnormal small bowel histology; with aberrant intraepithelial lymphocytosis of > 20 aberrant intraepithelial lymphocytes (IEL) per 100 CD45+ cells as determined by flow cytometry (or >50% if determined by immunohistochemistry); despite adherence to a strict GFD for at least 6 months; and after exclusion of other potential causes of symptomatic non-response (e.g., microscopic colitis, bacterial overgrowth, lactose intolerance, exocrine pancreatic insufficiency, hyperthyroidism, etc.) and intestinal histological abnormality (autoimmune enteropathy, giardiasis, immunodeficiency, collagenous sprue, Whipple*s disease, etc.).;NOTE: Subjects who have been treated for RCD-II must continue to have increased aberrant IELs (>20% by flow cytometry or 50% by IHC) and abnormal small bowel histology (Marsh *1) and must have had prior history of symptoms, however symptoms are not required of previously treated subjects, or subjects being treated with steroids, at the time of study entry. ;5. Total attempted adherence to a GFD for at least 6 consecutive months prior to screening. Subjects must also agree to make no changes to their current GFD for the duration of study participation.
6. Anti-tissue transglutaminase (IgA and IgG) at screening <2 x the diagnostic level for celiac disease (weak positive or negative).
7. Human leukocyte antigen DQ (HLA-DQ) typing compatible with celiac disease provided or obtained prior to baseline biopsy.
8. Life expectancy > 4 months.
9. Laboratory values:
a) Estimated creatinine clearance (CCr) > 30 mL/min/1.73m2 using the Cockcroft-Gault equation
b) Serum alkaline phosphatase (AP), alanine transaminase (ALT/SGPT), and aspartate aminotransferase (AST/SGOT) less than 3x the upper limits of normal (ULN)
c) Total bilirubin of less than 2.5 x ULN
d) Total white blood cell count (WBC) > 300/mm3
e) Platelet count > 85,000/mm3
f) INR less than 1.5
g) Albumin of more than 10 g/L (i.e., 1 g/dL or 1.45 mol/L)
10. Subjects receiving systemic steroids must be on a stable dose for at least 4 weeks prior to randomization, the dose should not exceed 20 mg of prednisone, prednisolone or equivalent per day. Oral budesonide will be accepted at a maximum dose of 9 mg per day.
11. Willingness and ability to comply with study procedures and protocol stipulated concomitant medication guidelines

Exclusion Criteria

1. Diagnosis of Type I Refractory Celiac Disease (RCD-I) or enteropathy-associated T cell lymphoma (EATL, excluded by the site*s standard imaging techniques for this purpose).
2. Presence of any of the following related to infection:
a) Active acute infection requiring systemic antibiotic, parenteral antifungal, or systemic antiviral treatments
b) Severe infection within the 3 months prior to screening
c) History of tuberculosis (TB)
d) Positive Interferon Gamma Release Assay (IGRA) test at screening OR known recent exposure (within 6 months prior to screening) to a patient with active TB; the subject can be enrolled if he or she has been successfully treated with appropriate chemoprophylaxis.
e) History within the 3 years prior to screening of an opportunistic infection typical of those seen in immunocompromised subjects (e.g., systemic candida infection, or systemic fungal infection).
3. Current diagnosis or history of cancer within the past 5 years, except RCD-II, successfully-treated basal cell or squamous cell carcinoma, cervical carcinoma-in-situ, or early stage prostate cancer
4. History or presence of clinically significant disease that in the opinion of the Investigator would confound the subject*s participation and follow-up in the clinical trial or put the subject at unnecessary risk including but not limited to:
a) Cardiovascular disease [e.g., uncontrolled hypertension (defined as office systolic blood pressure [BP] equal to or greater than 180 mmHg or office diastolic BP equal or greater than 110 mm/Hg), unstable angina, congestive heart failure worse than the New York Heart Association Class II, coronary angioplasty or myocardial infarction within the last 6 months, uncontrolled atrial or ventricular cardiac arrhythmias clinically significant pleural or pericardial effusion or ascites)
b) pulmonary disease (e.g., severe chronic pulmonary disease)
c) renal, hematological, gastrointestinal, endocrine (e.g., poorly controlled diabetes), immunologic, dermatologic, neurological, or psychiatric disease
5. History of significant immune suppression:
- Bone marrow transplant (BMT) or cladribine therapy less than 6 months prior to baseline. In other words, cladribine and bone marrow transplant naïve, primary non-responders (treatment resistant), secondary non-responders (relapse after response/remission) and incomplete responders may be enrolled in the study if cladribine therapy and/or BMT were not provided within the 6 months prior to randomization.
- Potent systemic immune suppressants (e.g., azathioprine) in the 3 months prior to baseline.
6. History of alcohol or drug abuse that would interfere with the ability to comply with the study protocol.
7. History of clinically significant hypersensitivity to the study drug or any related drugs or to any of the excipients.
8. Positive hepatitis B (Hep B), hepatitis C (Hep C), or Human immunodeficiency virus (HIV) infection test results at the time of screening.
9. Females who are pregnant or are planning to become pregnant during the study participation period or 6 months after last dose, or are currently breastfeeding.
10. Participation in another investigational drug or device study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to randomization
11. Any additional reason, which in the opinion of the Investigator, would prevent the subject from safe

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint:<br /><br>* Immunological Response 1: Reduction from baseline in the % of aberrant<br /><br>intestinal intraepithelial lymphocytes (IELs) vs total IELs as assessed by<br /><br>flow-cytometry </p><br>

Secondary Outcome Measures