Back to resultsSafety and Efficacy Study of TLL018 in the Treatment of Ulcerative Colitis
Primary Purpose
Ulcerative Colitis
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TLL018
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis
Eligibility Criteria
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).
Sites / Locations
- Gastroenterology Research of San Antonio (GERSA)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Low dose TLL018,BID
Middle dose TLL018,BID
High dose TLL018,BID
Placebo
Arm Description
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Placebo twice daily for 8 weeks.
Outcomes
Primary Outcome Measures
Percentage of subjects who achieved clinical remission per adapted Mayo score at 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.
Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
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.
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.
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.
Secondary Outcome Measures
Percentage of subjects with endoscopic improvement at Week 8
Percentage of subjects with endoscopic remission at Week 8
Percentage of subjects achieving clinical response per adapted Mayo score at Week 8
Percentage of subjects achieving clinical response per partial adapted Mayo score at Week 2
Percentage of subjects who achieved histologic-endoscopic mucosal improvement (as defined by endoscopic subscore and Geboes score) at Week 8
Percentage of subjects with mucosal healing (as defined by the endoscopic and histologic variables) at Week 8
Percentage of subjects who achieved histologic improvement (as defined by Geboes score) at Week 8
Percentage of subjects who reported no bowel urgency (as monitored electronically via a handheld device) at 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.
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.
Time to improvement as measured by rectal bleeding via handheld device
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05121402
Brief Title
Safety and Efficacy Study of TLL018 in the Treatment of Ulcerative Colitis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Decisions made by senior management of the company
Study Start Date
December 30, 2022 (Anticipated)
Primary Completion Date
July 1, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TLL Pharmaceutical, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
A study to investigate the safety and efficacy of TLL018 compared with placebo in subjects with moderate to severe ulcerative colitis.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low dose TLL018,BID
Arm Type
Experimental
Arm Description
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Arm Title
Middle dose TLL018,BID
Arm Type
Experimental
Arm Description
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Arm Title
High dose TLL018,BID
Arm Type
Experimental
Arm Description
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo twice daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
TLL018
Intervention Description
a TYK2/JAK1 inhibitor
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
a TLL018 Placebo
Primary Outcome Measure Information:
Title
Percentage of subjects who achieved clinical remission per adapted Mayo score at Week 8
Time Frame
Baseline to Week 8
Title
Number of treatment-emergent adverse events (TEAEs)
Description
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
Title
Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
Time Frame
Up to 8 weeks
Title
Number of Participants With Clinically Significant Changes in clinical laboratory data
Description
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
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description
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
Title
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
Description
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 Outcome Measure Information:
Title
Percentage of subjects with endoscopic improvement at Week 8
Time Frame
Week 8
Title
Percentage of subjects with endoscopic remission at Week 8
Time Frame
Week 8
Title
Percentage of subjects achieving clinical response per adapted Mayo score at Week 8
Time Frame
Week 8
Title
Percentage of subjects achieving clinical response per partial adapted Mayo score at Week 2
Time Frame
Week 2
Title
Percentage of subjects who achieved histologic-endoscopic mucosal improvement (as defined by endoscopic subscore and Geboes score) at Week 8
Time Frame
Week 8
Title
Percentage of subjects with mucosal healing (as defined by the endoscopic and histologic variables) at Week 8
Time Frame
Week 8
Title
Percentage of subjects who achieved histologic improvement (as defined by Geboes score) at Week 8
Time Frame
Week 8
Title
Percentage of subjects who reported no bowel urgency (as monitored electronically via a handheld device) at Week 8
Time Frame
Week 8
Title
Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score
Description
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.
Time Frame
Baseline to Week 8
Title
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Questionnaire Score
Description
The FACIT system is a collection of quality of life (QOL) questionnaires targeted to the management of cancer and other chronic illnesses.
Time Frame
Baseline to Week 8
Title
Time to improvement as measured by rectal bleeding via handheld device
Time Frame
Baseline to Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Facility Information:
Facility Name
Gastroenterology Research of San Antonio (GERSA)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Safety and Efficacy Study of TLL018 in the Treatment of Ulcerative Colitis
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