Inflammatory Bowel Disease Ulcerative Colitis
Conditions
Interventions
Both groups are treated with adalimumab for 8 weeks, per standard dose as
prescribed
1 group takes 1 tablet of AMT-101 once a day. The other group takes 1 placebo
tablet once a day
Sponsors
Applied Molecular Tranport Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The study will enroll male and female adult subjects with moderate to severe UC. Inclusion criteria (subjects must meet the following criteria to be randomized into the study): 1. Male and female subjects aged 18 to 75 years, inclusive. 2. Diagnosis of UC for at least 3 months prior to screening. 3. Moderate to severe UC, as defined by a total MCS of 6 to 12 inclusive at baseline, with a MES >= 2 (confirmed by central reader). 4. Eligible for adalimumab (or adalimumab biosimilar) therapy. 5. Naïve to therapy with approved or investigational biologics/tofacitinib including any anti-tumor necrosis factor (TNF) therapy, vedolizumab, or ustekinumab. 6. If subjects are receiving the following treatments, they must be on a stable dose for at least 4 weeks prior to randomization: a. 5-aminosalicylates (5-ASAs) (not exceeding 4.8 g per day). b. Oral corticosteroids (not exceeding prednisone 20 mg, budesonide 9 mg, or equivalent). c. 6-mercaptopurine (6-MP) (any stable dose). d. Azathioprine (AZA) (any stable dose). e. Methotrexate (MTX) (any stable dose). Note: subjects may be using 5-ASA and only 1 of the other medications listed (oral corticosteroids/6 MP/AZA/MTX). 7. If subjects are receiving bile-salt sequestrant, they must be on a stable dose for at least 3 months prior to randomization. 8. If subjects are receiving any nonprohibited medications, they must agree to maintain stable doses of concomitant medications for UC until the end of the safety follow-up period. 9. Unlikely to conceive. 10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and at the randomization visit prior to the first dose of study drug. 11. Able to participate fully in all aspects of this clinical trial. 12. Written informed consent must be obtained and documented.
Exclusion criteria
Exclusion criteria: 1. A diagnosis of Crohn*s disease (CD), indeterminate colitis, or presence or history of fistula with CD. 2. Disease activity limited to distal 15 cm (proctitis). 3. Current evidence of toxic megacolon, abdominal abscess, symptomatic colonic stricture, or stoma. 4. History or current evidence of colonic dysplasia or adenomatous colonic polyps. 5. Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile;; known active cytomegalovirus infection; known infection with hepatitisB or C virus; known infection with human immunodeficiency virus; infection requiring hospitalization or intravenous (IV) antimicrobial therapy, or opportunistic infection within 6 months prior to screening; any infection requiring antimicrobial therapy within 2 weeks prior to screening; history of more than 1 episode of herpes zoster or any episode of disseminated zoster. 6. A positive diagnostic tuberculosis (TB) test at screening (defined as a positive QuantiFERON test). In cases where the QuantiFERON test is indeterminate, the participant may have the test repeated once and if their second test is negative, they will be eligible. In the event a second test is also indeterminate, or QuantiFERON is unavailable, the investigator has the option to perform a purified protein derivative (PPD) skin test. If the PPD reaction is < 5 mm, then the subject is eligible. If the reaction is >= 5 mm, or PPD testing is not done, the subject is not eligible. An exception is made for subjects with a history of latent TB who are currently receiving treatment for latent TB, will initiate treatment for latent TB before the first dose of study treatment, or have documentation of completing appropriate treatment for latent TB within 3 years prior to the first dose of study treatment. 7. Live virus vaccination within 1 month prior to screening. 8. Any prior treatment with an approved or investigational biologic/tofacitinib, including anti-TNF therapy, vedolizumab, or ustekinumab. 9. Treatment with sirolimus, cyclosporine, mycophenolate, or tacrolimus within 8 weeks prior to randomization. 10. Treatment with IV corticosteroids, rectal corticosteroids, or rectal 5-ASA within 4 weeks prior to randomization. 11. Fecal microbiota transplantation within 1 month prior to screening. 12. A concurrent clinically significant, serious, unstable, or uncontrolled underlying cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound the study results, pose additional risk to the subject, or interfere with the subject*s ability to participate fully in the study. 13. A diagnosis of multiple sclerosis or optic neuritis, or history of a demyelinating disorder. 14. Known primary or secondary immunodeficiency. 15. History of myocardial infarction, unstable angina, transient ischemic attack, decompensated heart failure requiring hospitalization, congestive heart failure (New York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac revascularization, stroke, uncontrolled hypertension, or uncontrolled diabetes within 6 months of screening. 16. Clinically meaningful laboratory abnormalities at screening that would affe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Mean change in UC-100 score from baseline Mean change in Robarts Histopathology Index (RHI) from baseline • Mean change in total Mayo Clinic Score (MCS) and component scores (Mayo Endoscopic Subscore [MES], partial MCS, rectal bleeding, and stool frequency) from baseline • Mean change in faecal calprotectin from baseline • Mean change in highly sensitive C-reactive protein value (hs-CRP) from baseline • Endoscopic remission rate (defined as an MES of 0 or 1) • Endoscopic response rate (defined as a decrease in MES of at least 1 point from baseline) • Mucosal healing (defined as MES of 0 or 1 and a Geboes histological index score of | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory endpoints • Levels of AMT-101, AMT-101 anti-drug antibodies (ADAs), total interleukin-10 (IL-10), adalimumab, and adalimumab ADAs in serum • Concentrations of AMT-101, AMT-101 ADAs and total IL-10 in mucosal tissue biopsies • Mean change on the Symptoms and Impact questionnaire for UC (SIQ-UC) from baseline • Mean change in inflammatory bowel disease questionnaire score from baseline • Change in the number of white blood cells • Change in faecal matrix metalloproteinase 9 (MMP-9) • Change in faecal lactoferrin • Change in interleukin-1 receptor antagonist (IL-1Ra) • Change in protein content in serum and mucosal tissue • Change in gene expression in the mucosa • Change in cell populations in the mucosa • Change in the faecal microbiome | — |
Countries
Netherlands
Outcome results
None listed