Tibulizumab Systemic Sclerosis Understanding and Response Evaluation (TibuSURE)

• Tibulizumab (Biological), also known as ZB-106: Anti BAFF/IL-17 antibody
• Placebo (Other), also known as ZB-106 placebo: Placebo (inactive)

Primary outcomes

• [Period 1] Change from baseline in modified Rodnan Skin Score (mRSS) at 24 weeks [Week 24]: The mRSS assesses skin thickness at 17 different cutaneous sites across the body using a scale from 0 (normal skin) to 3 (severe thickening), with a total score ranging from 0 (no thickening) to 51 (severe thickening in all 17 areas)
• [Period 2] Safety and tolerability of tibulizumab [Week 52]: Assessed by the incidence of all treatment-emergent adverse events (TEAEs), as well as changes from baseline in vital signs, electrocardiogram (ECG) parameters, and laboratory results

Secondary outcomes

• [Period 1] Change from baseline in quantitative interstitial lung disease (QILD) obtained with high-resolution quantitative tomography (HRCT) in the whole lung in participants with SSc-interstitial lung disease (ILD) [Week 24]: HRCT measures the extent of interstitial lung disease by quantifying the amount of lung fibrosis, ground-glass opacity, and honeycomb lung, which are used to calculate the QILD score (scores can range from 0 to 100%, with higher scores indicating greater disease extent)
• [Period 1] Change from baseline in forced vital capacity (FVC) in participants with SSc-ILD [Week 24]: FVC is the amount of air that can be forcibly exhaled after the deepest possible breath
• [Period 1] Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) [Week 24]: HAQ-DI evaluates patients' self-assessed degree of disability across eight categories, with scores ranging from 0 to 3, where 3 indicates the worst degree of disability
• [Period 1] Safety and tolerability of tibulizumab [Week 24]: Assessed by the incidence of all TEAEs, as well as changes from baseline in vital signs, ECG parameters, and laboratory results
• [Period 2] Change from baseline in mRSS [Week 52]: The mRSS assesses skin thickness at 17 different cutaneous sites across the body using a scale from 0 (normal skin) to 3 (severe thickening), with a total score ranging from 0 (no thickening) to 51 (severe thickening in all 17 areas)
• [Period 2] Change from baseline in QILD obtained with HRCT in the whole lung in participants with SSc-ILD [Week 52]: HRCT measures the extent of interstitial lung disease by quantifying the amount of lung fibrosis, ground-glass opacity, and honeycomb lung, which are used to calculate the QILD score (scores can range from 0 to 100%, with higher scores indicating greater disease extent)

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Male or female, 18 to 75 years of age
* Body mass index between 18.0 and 38.0 kg/m²
* Fulfills classification criteria for SSc according to ACR/EULAR 2013 criteria
* Has diffuse cutaneous SSc, defined as mRSS >0 over at least one skin area proximal to the elbows and/or knees, in addition to acral fibrosis
* Has had SSc (defined as the first non-Raynaud's phenomenon (RP) symptom or sign attributed to SSc) for ≤7 years
* mRSS ≥15 and ≤45 at screening. Additional requirements for participants ≥2 years to ≤7 years from SSc onset and RNA Polymerase III antibody positive
* FVC >50% predicted
* Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% predicted (corrected for hemoglobin)

Exclusion Criteria:

* Has any of the following complications:

  * Left ventricular failure
  * Pulmonary arterial hypertension
  * Renal crisis within previous 6 months
  * Gastrointestinal dysmotility within previous 3 months
  * Digital ischemia with gangrene, amputation, or unscheduled hospitalization within previous 3 months
* Current rheumatic disease other than SSc that could interfere with assessment of SSc
* Lung disease requiring continuous oxygen therapy
* Evidence or suspicion of active or latent tuberculosis
* Active Crohn's Disease or ulcerative colitis

• Study Director, Study director, Zura Bio Inc