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

TLL Pharmaceutical

Status and phase: Withdrawn; Phase 2

Conditions: Ulcerative Colitis

Treatments: Other: Placebo; Drug: TLL018

Study type: Interventional

Funder types: Industry

Identifiers

NCT05121402

TLL018-202

Details and patient eligibility

About

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

Full description

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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 4 patient groups, including a placebo group

Low dose TLL018,BID

Experimental group

Description:

Drug: TLL018 all subjects will receive TLL018 for 8 weeks

Treatment:

Drug: TLL018

Middle dose TLL018,BID

Experimental group

Description:

Drug: TLL018 all subjects will receive TLL018 for 8 weeks

Treatment:

Drug: TLL018

High dose TLL018,BID

Experimental group

Description:

Drug: TLL018 all subjects will receive TLL018 for 8 weeks

Treatment:

Drug: TLL018

Placebo

Placebo Comparator group

Description:

Placebo twice daily for 8 weeks.

Treatment:

Other: Placebo