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

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

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.