A Randomized, Double-blinded, Placebo-controlled, Multicenter Phase 2 Study Evaluating the Efficacy and Safety of TLL018 in Participants With Moderate-to-severe Plaque Psoriasis

Hangzhou Highlightll Pharmaceutical Co., Ltd35 sites in 1 country82 target enrollmentJanuary 19, 2023

ConditionsPlaque Psoriasis

InterventionsTLL018 tablets

DrugsTLL018 tablets

Overview

Phase: Phase 2
Intervention: TLL018 tablets
Conditions: Plaque Psoriasis
Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd
Enrollment: 82
Locations: 35
Primary Endpoint: proportion of participants achieving PASI-75
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 2, multicenter, randomized, double-blinded, parallel dose group, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of 2 doses of TLL018 as therapy in approximately 90 participants with moderate-to-severe PP.

Registry

clinicaltrials.gov

Start Date

January 19, 2023

End Date

December 23, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hangzhou Highlightll Pharmaceutical Co., Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Are between the ages of 18 and 75 years, inclusive, at time of informed consent.
•Capable of giving informed consent and complying with study procedures.
•Willing and able to adhere to study restrictions.
•Laboratory and medical history parameters within the protocol defined ranges.
•Normal renal function (\>90 mL/min/1.72 m2) or mild renal impairment (Stage 2 mild chronic kidney disease glomerular filtration rate \[GFR\] = 60 to 89 mL/min/1.73 m2) as determined by central laboratory.
•Body mass index (BMI) of 18.0 to 35.0 kg/m2 inclusive.
•Have had a diagnosis of moderate-to-severe PP for at least 6 months prior to Baseline.
•Participants with moderate-to-severe PP covering ≥10% body surface area (BSA), with a Psoriasis Area and Severity Index (PASI) ≥12 and a static Physician's Global Assessment (PGA) score ≥3 at Baseline.
•Participants with plaque psoriasis who are systemic treatment naïve or have received at least one of the conventional anti-psoriasis treatments such as acitretin, phototherapy, methotrexate, cyclosporine, apremilast, or biologic therapy (anti-TNF or anti-IL-12/17/23).
•Participants who are candidates for systemic treatment for psoriasis at the discretion of the Investigator.

Exclusion Criteria

•Pregnant or nursing women.
•Past history of gastrointestinal perforation, history of peptic ulcers and/or regular use of NSAIDs.
•History of chronic alcohol or drug abuse within 6 months prior to Screening as determined by the Investigator based on medical history and patient interview.
•Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, neurologic, or psychiatric disease.
•Current and/or recent history (\<30 days prior to Screening and/or \<45 days prior to randomization) of a clinically significant viral, bacterial, fungal, parasitic, or mycobacterial infection.
•Subject is currently being treated with or has received strong cytochrome P450 3A (CYP3A4) inhibitors, such as itraconazole, within 4 weeks prior to Baseline (Day 0).
•Any history of malignancies, except for non-recurrent basal cell skin cancer, squamous cell skin cancer, and cervical cancer in situ that are considered to be cured.
•Tests positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). For Hepatitis B all subjects will undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core Antibody (HBcAb). Subjects who are HBsAg positive are not eligible for the study. Subjects who are HBsAg negative and HBcAb positive will subsequently need testing for Hepatitis B virus deoxyribonucleic acid (HBV DNA) and if HBV DNA negative may be enrolled in the study; if HBV DNA is positive, the subject is not eligible for the study. Positive hepatitis C virus result is defined as having a positive hepatitis C antibody test with a positive confirmatory hepatitis C polymerase chain reaction test.
•Recent exposure to active tuberculosis (TB). Current evidence of active TB or current evidence of latent TB. Participants with positive TB test (e.g., QuantiFERON) that have been treated for latent TB. A borderline QuantiFERON test should be repeated. If still indeterminant, then a chest x-ray may be performed (positive chest x-ray is exclusionary).
•History of unexplained syncope, symptomatic hypotension, or hypoglycemia.

Arms & Interventions

Cohort 2

TLL018 tables, 20 mg 1piece,BID

Intervention: TLL018 tablets

Cohort 3

TLL018 tables, 40 mg 1piece,BID

Intervention: TLL018 tablets

Cohort 4

placebo, 1piece,BID

Intervention: TLL018 tablets

Outcomes

Primary Outcomes

proportion of participants achieving PASI-75

Time Frame: Week12

A patient was a responser if a minimum 75% PASI improvement from Baseline was achieved including measure of the average redness (erythema), thickness (induration), and scaliness (scaling) In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t), and lower extremities (l).Each of these areas is assessed separately for erythema, induration, and scaling, which are rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows: 0 = no involvement 1. = 1% to 9% 2. = 10% to 29% 3. = 30% to 49% 4. = 50% to 69% 5. = 70% to 89% 6. = 90% to 100%. PASI = 0.1 (Eh + lh + Sh) Ah + 0.2 (Eu + lu + Su) Au + 0.3 (Et +lt + St) At + 0.4 (El +ll +Sl) Al

Secondary Outcomes

Proportion of participants achieving PASI-90(From week 4 to Weeks 12)
Proportion of participants achieving PGA score of 0 or 1(From week 4 to Weeks 12)
Proportion of participants achieving PASI-75 (except Week 12)(From week 4 to Weeks 12(except Week 12))