Safety and Efficacy Study of TLL018 in the Treatment of Ulcerative Colitis

TLL Pharmaceutical, LLC

Overview

A study to investigate the safety and efficacy of TLL018 compared with placebo in subjects with moderate to severe ulcerative colitis.

This is a phase 2, multicenter, randomized, double-blind, parallel dose groups, placebo-controlled dose ranging study to evaluate the safety and efficacy of 3 doses of TLL018 as an induction therapy in subjects with moderate to severe UC. Eligible subjects will be randomized to receive one of the following treatments: TLL018 low dose, TLL018 middle dose, TLL018 high dose, or placebo. All subjects may remain on a stable dose of conventional therapy used prior to enrollment. Subjects will be assessed for safety, tolerability, and response to treatment. Samples for pharmacokinetics (PK) and pharmacodynamics (PD) biomarker analyses will be collected throughout the study according to the Schedule of Assessments (SoA) for potential correlation to clinical outcomes. Further participation may continue beyond the initial 8 weeks for another 5-week Extension Period of therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Conditions

Ulcerative Colitis

Interventions

TLL018DRUG

a TYK2/JAK1 inhibitor

PlaceboOTHER

a TLL018 Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male and female subjects ≥ 18 and ≤ 75 years of age at baseline. * Capable of giving informed consent and complying with study procedures. * Normal renal function or mild renal impairment as determined by the Investigator following review of clinical laboratory test results. * Laboratory and medical history parameters within the protocol-defined ranges. * Diagnosis of UC for 90 days or greater prior to baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia, and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available. * Active UC with a full Mayo score of 6 to 12 points and endoscopic subscore of 2 or higher confirmed by central reader. * Subject must have received COVID-19 vaccine \>2 months before first dose of study drug. Exclusion Criteria: * Pregnant or nursing women. * Clinically significant history of cardiovascular, hematologic, renal, hepatic, bronchopulmonary, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator. * Current and/or recent history of a clinically significant infection. * Any history of malignancies, except for non-melanoma skin cancers (unless it is metastatic). * Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody. * Any condition or finding that in the Investigator's opinion would put the subjects or study conduct at risk if the subjects were to participate in the study. * Current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). * Current diagnosis of fulminant colitis and/or toxic megacolon, or active Clostridium difficile colitis. * Subject with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. * Subject with previous exposure to JAK inhibitor (eg, tofacitinib, baricitinib, filgotinib, upadacitinib).

Locations (1)

Gastroenterology Research of San Antonio (GERSA)

San Antonio, Texas, United States

Outcomes

Primary Outcomes

Percentage of subjects who achieved clinical remission per adapted Mayo score at Week 8

Time frame: Baseline to Week 8

Number of treatment-emergent adverse events (TEAEs)

TEAE defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.

Time frame: Up to 8 weeks

Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)

Time frame: Up to 8 weeks

Number of Participants With Clinically Significant Changes in clinical laboratory data

Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.

Time frame: Up to 8 weeks

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.

Time frame: Up to 8 weeks

Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings

Clinically significant ECG criteria included QT interval corrected using the Fridericia's formula (QTCF) value 450 msec and 30\<=change\<60.

Time frame: Up to 8 weeks

Secondary Outcomes

Percentage of subjects with endoscopic improvement at Week 8

Data from ClinicalTrials.gov

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