Ulcerative Colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Sponsors
Applied Molecular Transport Inc.
Eligibility
Sex/Gender
All
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 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Exclusion criteria (subjects who exhibit any of the following criteria are to be excluded from the study): 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 affect subject safety, as determined and documented by the investigator. 17. Pregna
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effects of AMT-101 in combination with adalimumab on ulcerative colitis (UC) disease activity as measured by symptoms, endoscopy, histology, and biomarkers;Secondary Objective: Secondary Objectives: - To evaluate the safety and tolerability of AMT-101 over 8 weeks - To assess the pharmacokinetic (PK) parameters of AMT-101 in combination with adalimumab - To assess health-related quality of life (HRQOL) - To assess the pharmacodynamic (PD) effect of AMT-101 on biomarkers - To assess target engagement and mechanism of action ;Primary end point(s): Mean change in UC-100 score from baseline ;Timepoint(s) of evaluation of this end point: Week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Weeks 2, 4, and 8;Secondary end point(s): Secondary Efficacy Endpoints: - 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 fecal calprotectin from baseline - Mean change in high-sensitivity C-reactive protein (hs CRP) from baseline - Endoscopic remission rate (defined as a MES of 0 or 1) - Endoscopic response rate (defined as a decrease from baseline in MES of at least 1 point) - Mucosal healing rate (defined as MES of 0 or 1 and a Geboes Histologic Index score of = 3.1) - Histologic remission rate (defined as Geboes Histologic Index score of = 2B.0; or Robarts Histopathology Index [RHI] = 3 with subscores of 0 for lamina propria neutrophils and 0 for neutrophils in epithelium) - Proportion of subjects who achieve a 50% reduction in RHI - Clinical remission rate (defined as total MCS = 2 with all subscores = 1) - Clinical response rate (defined as decrease from baseline in MCS of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1) - Clinical remission rate (alternative definition of Mayo stool frequency subscore of 0 or 1 and Mayo rectal bleeding subscore of 0 and MES of 0 or 1) Secondary Safety Endpoints: - Frequency and severity of adverse events (AEs) - Changes in clinical chemistry and hematology from baseline - Changes in vital signs and physical examinations from baseline - Electrocardiogram (ECG) findings Secondary Exploratory Endpoints: - Concentrations of AMT-101, AMT-101 antidrug 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 in Inflammatory Bowel Dise | — |
Countries
Georgia, Netherlands, Poland, Ukraine
Contacts
Public ContactClinical Trial AMT-101-202
Applied Molecular Transport Inc.
Outcome results
None listed