A Two-part, Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending-dose Study of PRO-203 in Healthy Adult Volunteers Followed by an Open-label, Single-ascending-dose With Priming Study of PRO-203 in Participants With Systemic Sclerosis
A two-part study of PRO-203 administered subcutaneously in healthy adult volunteers and participants with Systemic Sclerosis (SSc).
• Is male or female, age 18 to 65 years, inclusive, at Screening.
• Able to provide Informed Consent.
• Absolute B cell count \> 25 cells/uL.
∙ Additional Inclusion for Part 1 (Closed to Enrollment)
• In good general health, determined by no clinically significant findings in the of the investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Day -1 (participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment).
• Up to date vaccination status per local guidelines (including but not limited to influenza vaccine, COVID booster and hepatitis B vaccine).
∙ Additional Inclusion for Part 2
• Fulfill 2013 ACR/ EULAR criteria for classification of SSc with a total score of ≥ 9.
• Active disease defined as at least two of the following at screening:
• Disease duration ≤ 2 years (since onset of first-non-Raynaud-symptom), or
• Elevated acute phase reactant levels (CRP ≥ 6 mg/L, erythrocytes sedimentation rate \[ESR\] ≥ 28 mm/1h, or platelet count ≥ 330,000/µL), or
• Baseline mRSS ≥10 with evidence of progression, defined as mRSS increase at least 3 units, or involvement of 1 new body area and mRSS increase at least 2 units, or involvement of 2 new body areas (each within the previous 6 months), or
• ≥ 1 tendon friction rub, or
• Elevation of CK or aldolase \> 2 × the upper limit of normal (ULN) consistent with SSc-related myopathy, or
• Progressive fibrosing interstitial lung disease (ILD) as defined by at least one of the following criteria at any time within the prior 2 years:
‣ relative decline in forced vital capacity (FVC) % predicted ≥ 10%, or
⁃ relative decline in FVC % predicted ≥ 5% to \<10% and worsened respiratory symptoms, or
⁃ relative decline in FVC % predicted ≥ 5% to \<10% and increased extent of fibrosis on high-resolution computed tomography (HRCT), or
⁃ worsened respiratory symptoms and increased extent of fibrosis on HRCT
• Intolerant or refractory to at least 1 line of standard therapy, including methotrexate, azathioprine, IVIG, mycophenolic acid derivatives, cyclophosphamide, TNF-inhibitors, rituximab, or tocilizumab.