A Phase II Study of TollB-001 Tablets in Systemic Sclerosis

Official title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy and Safety of TollB-001 Tablets in Patients With Systemic Sclerosis

Overview

The goal of this Phase II study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of TollB-001 Tablets in adults aged 18 to 70 years (male or female) with systemic sclerosis (SSc).

Detailed description

Study Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of TollB-001 in Adult Patients with Systemic Sclerosis (SSc) Study Design: This is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of TollB-001 in adult patients with systemic sclerosis (SSc).

Sample Size and Target Population: A total of 36 patients with SSc are planned for enrollment. Eligible patients must have a disease duration of ≤ 60 months from the first onset of non-Raynaud's phenomenon and a modified Rodnan Skin Score (mRSS) between 10 and 40 (inclusive) at the screening visit.

Study Phases: The study consists of three sequential phases:

Screening Period: Up to 28 days

Treatment Period: 90 days, comprising:

Single-Dose Phase: 3 days (dosing on Day 1 only) Multiple-Dose Phase: 87 days (consecutive daily dosing from Day 4 through Day 87, for a total of 84 days of dosing) Follow-up Period: 28 days following the last dose

Interventions

• Drug TollB-001 Tablet
  TollB-001 Tablets
• Drug Placebo
  Placebo Tablets

Primary outcome measures

• Rodnan Skin Score (mRSS) [Time frame: up to 12 weeks]

Secondary outcome measures (12)

• Composite Response Index in Systemic Sclerosis (CRISS) [Time frame: up to 12 weeks]
• Forced Vital Capacity (FVC) [Time frame: up to 12 weeks]
• Health Assessment Questionnaire- Disability Index (HAQ-DI) [Time frame: up to 12 weeks]
• Patient Global Assessment (PtGA) [Time frame: up to 12 weeks]
• Incidence and Severity of Adverse Events [Time frame: up to 12 weeks]
• Incidence and Severity of Adverse Reactions [Time frame: up to 12 weeks]
• Incidence of Serious Adverse Events [Time frame: up to 12 weeks]
• Incidence of Serious Adverse Reactions [Time frame: up to 12 weeks]
• The four major vital signs, including body temperature, pulse (heart rate), respiration, and blood pressure. [Time frame: up to 12 weeks]
• The 12-lead electrocardiogram (ECG) includes parameters such as heart rate, RR interval, PR interval, QT interval, QRS interval, and the corrected QT interval (QTcf, where QTcf = QT / RR^0.33). [Time frame: up to 12 weeks]
• Routine blood test includes parameter such as white blood cell, lymphocyte count and percentage, neutrophil count and percentage, monocyte count and percentage, eosinophil count, basophil count, , red blood cell, hemoglobin, hematocrit, platelet count. [Time frame: up to 12 weeks]
• Blood biochemical parameters such as: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, indirect bilirubin, total protein, albumin, alkaline phosphatase, gamma-glutamyl transferase (GGT) and urea, etc. [Time frame: up to 12 weeks]

Eligibility criteria

Inclusion criteria

• Aged 18 to 70 years (inclusive), male or female.
• Diagnosis of systemic sclerosis (SSc) according to the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria.
• Meeting the classification criteria for diffuse cutaneous systemic sclerosis (dcSSc) as defined in the 2022 Chinese Guideline for the Diagnosis and Treatment of Systemic Sclerosis.
• Evidence of active disease at screenin.
• Female participants of childbearing potential and male participants must use effective contraception during the study and for 3 months after the last dose of study drug. Male participants whose partners are females of reproductive potential must agree to use effective contraception and refrain from donating sperm during the study and for 3 months after the last dose. Female participants of childbearing potential must have a negative pregnancy test.
• Able to swallow all study medications.
• Willing and able to comply with the study protocol (e.g., able to understand and complete questionnaires, adhere to visit schedules, and take study medication) and provide signed informed consent.

Exclusion criteria

• Known hypersensitivity to any active ingredient or excipient of the study drug, or to drugs of the same class.
• History of scleroderma renal crisis within 6 months prior to randomization.
• Clinically significant chronic intermittent bleeding within 4 weeks prior to screening (e.g., active gastric antral vascular ectasia, active peptic ulcer, or duodenal ulcer), or participants at risk of bleeding.
• Any active malignancy or history of malignancy.
• Presence of severe, uncontrolled diseases.
• Major surgery within 8 weeks prior to randomization, or expected to undergo major surgery after enrollment.
• Drug or alcohol abuse or dependence at screening, or a history of drug or alcohol abuse or dependence within 6 months prior to randomization.
• Participation in another clinical trial within 3 months prior to the date of informed consent, or planning to participate in another clinical trial during the study period.
• Participants who, in the investigator's judgment, are unsuitable for participation in this clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Toll Biotech, 2108-B007, No. 9 West Beisihuan Road, Haidian District, Beijing, People's Re — Beijing
• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijing

Identifiers

NCT: NCT07745725 · TLBT-TollB-001-SSC-II · CTR20261937

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20261937 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗