A Randomized, Placebo-controlled, Double-blind, Parallel-group, Exploratory, Phase 2 Study of the Efficacy and Safety of Oral AMT-101 in Combination with Adalimumab in Subjects with Moderate to Severe Ulcerative Colitis

Phase 2

Completed

Conditions: Inflammatory Bowel Disease
Ulcerative Colitis
10017969

Registration Number: NL-OMON51097

Lead Sponsor: Applied Molecular Tranport Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 4

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

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