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 modified MCS of 6 to 12 inclusive at baseline, with a MES = 2 (confirmed by central reader). 4. If subjects have previously received any biologic (i.e., tumor necrosis factor [TNF] antagonists, vedolizumab, ustekinumab) or tofacitinib therapy, they must meet the following: a. Biologics: a washout period of at least 8 weeks prior to randomization, or a washout period of at least 4 weeks prior to randomization if biologic drug levels are undetectable. b. Tofacitinib: a washout period of at least 4 weeks prior to randomization. c. Cannot have failed both biologic and tofacitinib. Note: No more than 51 subjects (50% of the total sample) with prior exposure to these therapies will be randomized into the study including no more than 20 subjects (20% of the total sample) with exposure to more than 1 of these therapies. 5. 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). 6. If subjects are receiving bile-salt sequestrant, they must be on a stable dose for at least 3 months prior to randomization. 7. 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. 8. Unlikely to conceive. 9. 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. 10. Able to participate fully in all aspects of this clinical trial. 11. 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 87 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
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, active Tuberculosis infection; known infection with hepatitis B 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. Live virus vaccination within 1 month prior to screening. 7. Treatment with methotrexate, sirolimus, cyclosporine, mycophenolate, or tacrolimus within 4 weeks prior to randomization. 8. Treatment with IV corticosteroids, rectal corticosteroids, or rectal 5-ASA within 4 weeks prior to randomization. 9. Fecal microbiota transplantation within 1 month prior to screening. 10. 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. 11. Known primary or secondary immunodeficiency. 12. 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. 13. Clinically meaningful laboratory abnormalities at screening that would affect subject safety, as determined and documented by the investigator. 14. Pregnant or lactating females. 15. Any surgical procedure requiring general anesthesia within 1 month prior to screening, or planned elective surgery during the study. 16. History of malignant neoplasms or carcinoma in situ within 5 years prior to screening. 17. Current or recent history of alcohol dependence or illicit drug use that, in the opinion of the investigator, may interfere with the subject’s ability to comply with the study procedures. 18. Mental or legal incapacitation or a history of clinically significant psychiatric disorders at the time of screening visit that would impact the ability to participate in the trial according to the investigator. 19. Unable to attend study visits or comply with procedures. 20. Concurrent participation in any other interventional study or received any investigational therapy within 1 month of randomization. 21. Previous exposure to AMT-101 or recombinant human interleukin-10 (rhIL-10). 22. A known hypersensitivity to AMT-101 or its excipients. 23. Current treatment with antimotility medications or antidiarrheals (except for bile-salt sequestrants).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of repeated oral doses of AMT-101 versus placebo to reduce Mayo Endoscopic Subscore (MES) at Week 12 in adult subjects with moderate to severe UC;Secondary Objective: Secondary Objectives: - To evaluate the effects of AMT-101 on disease activity as measured by symptoms, endoscopy, histology, and biomarkers over 12 weeks - To evaluate safety and tolerability of oral AMT-101 over 12 weeks - To assess the pharmacokinetic (PK) parameters of AMT-101 - To assess health-related quality of life (HRQOL) Exploratory Objectives: - To assess the pharmacodynamic (PD) effect of AMT-101 on inflammation - To assess the PK parameters of AMT-101 in mucosal tissue - To assess the PD effect of AMT-101 on biomarkers - To assess target engagement and mechanism of action;Primary end point(s): Mean change in MES (Mayo endoscopic subscore) from baseline to Week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: - Endoscopic remission rate at Week 12 (defined as a MES of 0 or 1) - Endoscopic response rate at Week 12 (defined as a decrease from baseline in MES of at least 1 point) - Mucosal healing rate at Week 12 (defined as MES of 0 or 1 and a Geboes Histologic Index score of = 3.1) - Histologic remission rate at Week 12 (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) - Clinical remission rate at Week 12 (defined as total MCS = 2 with all subscores = 1) - Clinical response rate at Week 12 (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) - Mean change in partial MCS from baseline to Weeks 2, 6, and 12 - Mean change in Mayo rectal bleeding subscore from baseline to Weeks 2, 6, and 12 - Mean change in Mayo stool frequency subscore from baseline to Weeks 2, 6, and 12 - Proportion of subjects with a Geboes Histologic Index score = 3.1 at Week 12 - Mean change in RHI scores from baseline to Week 12 - Mean change in fecal calprotectin from baseline to Weeks 2, 6, and 12 - Mean change in high-sensitivity C-reactive protein (hs-CRP) from baseline to Weeks 2, 6, and 12 Secondary Safety Endpoints: - Frequency and severity of adverse events (AEs) compared to placebo - Changes in clinical chemistry and hematology from baseline - Results of vital signs and physical examination - Electrocardiogram (ECG) findings Secondary PK Endpoints: - Concentrations of AMT-101, AMT-101 antidrug antibodies (ADAs), and total IL-10 in serum at Week 12 Secondary HRQOL Endpoints: - Mean change in Symptoms and Impacts Questionnaire for UC (SIQ-UC) from baseline to Week 12 - Mean change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from ba | — |
Countries
Belarus, Belgium, Bulgaria, Canada, Czech Republic, France, Georgia, Germany, Hungary, India, Italy, Kazakhstan, Moldova, Republic of, Netherlands, Poland, Romania, Russian Federation, Serbia, Spain, Switzerland, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial AMT-101-202
Applied Molecular Transport Inc.
Outcome results
None listed