T-Guard in dcSSc

Prior treatment

• On continuous oxygen therapy
• Known active infection with Hepatitis B, C, or E at screening (prior infections are not excluded), HIV or HTLV1 positivity.
• Participants who continue to receive any systemic treatment for systemic sclerosis, other than MTX or MMF, including but not limited to azathioprine, cyclosphosphamide, IVIG, rituximab, and tocilizumab, within three months prior to the baseline visit will be excluded. Continuation of oral corticosteroids (≤10 mg/day of prednisone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) is permitted if the participant is on a stable dose for at least two weeks prior to and including the baseline visit.

Other illness

• Latent infection with mycobacterium tuberculosis, unless history of treatment.
• Malignancy within the past 5 years, except for non-melanoma skin cancer or cervical cancer situ.
• Uncontrolled infection (infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present) are not eligible for this trial.
• Known hypersensitivity to any of the components of murine monoclonal antibodies (mAb), or Recombinant Ricin Toxin A-chain (RTA).
• Echocardiographic features consistent with pulmonary hypertension, unless right heart catheterization (RHC) is normal
• Moderate to severe restrictive lung disease defined as FVC <50% predicted and/or DLCO Hb-corrected <45% predicted and presence of ILD on HRCT

Lab values

• Creatinine greater than or equal to 2mg/dL or creatinine clearance less than 60 mL/min or requiring hemodialysis. History or presence of glomerulonephritis, acute tubular necrosis, and/or interstitial nephritis or clinically significant findings as determined by urinalysis at screening
• White blood cell count (WBC) <3000 µl
• Platelets <100,000/mm3
• Evidence of heart failure defined as left ventricular ejection fraction (LVEF) <45% as assessed by either echocardiography or multigated acquisition (MUGA) scan in the last 6 months
• Albumin of less than or equal to 25 g/L
• Creatine kinase (CK) level greater than 5 times the upper limit of normal (ULN)
• Hemoglobulin (Hb) <9 g/dl

Other

• Significant gastrointestinal (GI) dysmotility requiring total parenteral nutrition or G or J tube
• Vascular prosthesis.
• Need for mechanical ventilation and/or vasopressor support or requiring hemodialysis.
• Patients who have been diagnosed with scleroderma renal crisis (SRC) or another cause TMA anytime during their lifetime.

• Aged between 18-75 at the time of signing informed consent.
• With early dcSSc, defined as skin involvement above and below elbows and/or knees, disease duration ≤36 months from first non-Raynaud phenomenon.
• Modified Rodnan skin scores (MRSS) scores ≥15
• Progressive skin or musculoskeletal (MKS)disease, e.g. worsening of skin with new areas of involvement or tendon friction rubs (TFR), with either Health Assessment Questionnaire Disability Index (HAQ-DI) >1.0 or elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP).
• Interstitial lung disease (ILD) with forced vital capacity (FVC) 50-<80% predicted or lung diffusion testing (DLCO)(Hb corrected) 45-75% or >10% lung involvement on visual rad high-resolution computed tomography (HRCT) scan or those with progressive ILD, defined as progressive pulmonary fibrosis (PPF)-ILD in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851481/.
• Participants should have failed at least one established systemic immunosuppressive treatment for dcSSc (e.g., MTX, MMF , azathioprine, rituximab, tocilizumab, intravenous immunoglobulin [IVIG], or cyclophosphamide), each tried for at least 3 months, and: a. Have received treatment with MTX or MMF for at least 3 months prior to enrollment, with the dose stable for at least 8 weeks prior to enrollment; and b. Be able and willing, in the opinion of the investigator, to continue this background therapy at the stable dose throughout the study, unless dose reduction or discontinuation is clinically indicated due to adverse events.
• Participants should have given written informed consent