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

A Phase 2 Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of TLL018 for Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis

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

Study Overview

• Status: Withdrawn
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: TLL018; Other: Placebo

Detailed 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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Research of San Antonio (GERSA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose TLL018,BID; Drug: TLL018 all subjects will receive TLL018 for 8 weeks	Drug: TLL018; a TYK2/JAK1 inhibitor
Experimental: Middle dose TLL018,BID; Drug: TLL018 all subjects will receive TLL018 for 8 weeks	Drug: TLL018; a TYK2/JAK1 inhibitor
Experimental: High dose TLL018,BID; Drug: TLL018 all subjects will receive TLL018 for 8 weeks	Drug: TLL018; a TYK2/JAK1 inhibitor
Placebo Comparator: Placebo; Placebo twice daily for 8 weeks.	Other: Placebo; a TLL018 Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who achieved clinical remission per adapted Mayo score at Week 8		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.	Up to 8 weeks
Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)		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.	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.	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.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with endoscopic improvement at Week 8		Week 8
Percentage of subjects with endoscopic remission at Week 8		Week 8
Percentage of subjects achieving clinical response per adapted Mayo score at Week 8		Week 8
Percentage of subjects achieving clinical response per partial adapted Mayo score at Week 2		Week 2
Percentage of subjects who achieved histologic-endoscopic mucosal improvement (as defined by endoscopic subscore and Geboes score) at Week 8		Week 8
Percentage of subjects with mucosal healing (as defined by the endoscopic and histologic variables) at Week 8		Week 8
Percentage of subjects who achieved histologic improvement (as defined by Geboes score) at Week 8		Week 8
Percentage of subjects who reported no bowel urgency (as monitored electronically via a handheld device) at Week 8		Week 8
Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score	The IBDQ is used to measure disease specific quality of life on a 32 Likert-scaled items questionnaire. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function and social function with scores ranging from 10 to 70, 5 to 35, 12 to 84 and 5 to 35 respectively and the total score ranges from 32 to 224. Higher scores indicate better health related quality of life.	Baseline to Week 8
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Questionnaire Score	The FACIT system is a collection of quality of life (QOL) questionnaires targeted to the management of cancer and other chronic illnesses.	Baseline to Week 8
Time to improvement as measured by rectal bleeding via handheld device		Baseline to Week 8

Collaborators and Investigators

• Sponsor: TLL Pharmaceutical, LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 14, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: TLL018-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No