DAFSOLIMAB SETARITOX|GRISNILIMAB SETARITOX for Diffuse cutaneous systemic sclerosis

Inclusion criteria

• {"criterion_text":"- Aged between 18-75 at the time of signing informed consent.\n- With early dcSSc, defined as skin involvement above and below elbows and/or knees, disease duration ≤36 months from first non-Raynaud phenomenon.\n- Modified Rodnan skin scores (MRSS) scores ≥15\n- 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).\n- 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/.\n- 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.\n- Participants should have given written informed consent"}

Exclusion criteria

• {"criterion_text":"- 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\n- White blood cell count (WBC) <3000 µl\n- On continuous oxygen therapy\n- Significant gastrointestinal (GI) dysmotility requiring total parenteral nutrition or G or J tube\n- Latent infection with mycobacterium tuberculosis, unless history of treatment.\n- Known active infection with Hepatitis B, C, or E at screening (prior infections are not excluded), HIV or HTLV1 positivity.\n- Malignancy within the past 5 years, except for non-melanoma skin cancer or cervical cancer situ.\n- Vascular prosthesis.\n- Need for mechanical ventilation and/or vasopressor support or requiring hemodialysis.\n- 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.\n- Known hypersensitivity to any of the components of murine monoclonal antibodies (mAb), or Recombinant Ricin Toxin A-chain (RTA).\n- Platelets <100,000/mm3\n- 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.\n- 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\n- Echocardiographic features consistent with pulmonary hypertension, unless right heart catheterization (RHC) is normal\n- Moderate to severe restrictive lung disease defined as FVC <50% predicted and/or DLCO Hb-corrected <45% predicted and presence of ILD on HRCT\n- Patients who have been diagnosed with scleroderma renal crisis (SRC) or another cause TMA anytime during their lifetime.\n- Albumin of less than or equal to 25 g/L\n- Creatine kinase (CK) level greater than 5 times the upper limit of normal (ULN)\n- Hemoglobulin (Hb) <9 g/dl"}

Primary endpoints

• {"endpoint_text":"- Incidence of Grade 3 or higher adverse events (AEs), based on CTCAE v5, occurring in the period from the first T-Guard infusion until 28 days after the last T-Guard administration.","definition_or_measurement_approach":"Based on CTCAE v5; measured as incidence of Grade 3 or higher adverse events occurring from the first T-Guard infusion until 28 days after the last T-Guard administration."}

Secondary endpoints

• {"endpoint_text":"- Incidence of AEs occurring during 180 days after treatment start","definition_or_measurement_approach":"Incidence of adverse events occurring during the 180 days after treatment start."}
• {"endpoint_text":"- Incidence of infectious AEs occurring during 180 days after treatment start","definition_or_measurement_approach":"Incidence of infectious adverse events occurring during the 180 days after treatment start."}
• {"endpoint_text":"- Incidence of SAEs occurring during 180 days after treatment start, and - if considered related to T-Guard treatment - occurring in the period of 180 until 365 days after treatment start","definition_or_measurement_approach":"Incidence of serious adverse events during 180 days after treatment start; if related to T-Guard, also capture events occurring 180–365 days after treatment start."}
• {"endpoint_text":"- Incidence of AESIs occurring during 180 days after treatment start, and - if considered related to T-Guard treatment - occurring in the period of 180 until 365 days after treatment start: hypoalbuminemia; thrombocytopenia; microangiopathy.","definition_or_measurement_approach":"Incidence of adverse events of special interest (hypoalbuminemia; thrombocytopenia; microangiopathy) during 180 days after treatment start and, if related, during 180–365 days after treatment start."}
• {"endpoint_text":"- All-cause mortality during 365 days after treatment start","definition_or_measurement_approach":"All-cause mortality captured during 365 days after treatment start."}
• {"endpoint_text":"- Immunogenicity of T-Guard","definition_or_measurement_approach":"Assessment of immunogenicity (anti-drug antibodies) per protocol schedules."}
• {"endpoint_text":"- Pharmacokinetics of T-Guard","definition_or_measurement_approach":"Pharmacokinetic characterization of T-Guard in treated participants per protocol sampling schedule."}
• {"endpoint_text":"- Achieving revised CRISS-25 scores at study day 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Change in revised CRISS-25 score at study days 90, 180, 270 and 365 versus baseline."}
• {"endpoint_text":"- Achieving revised CRISS-50 scores at study day 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Change in revised CRISS-50 score at study days 90, 180, 270 and 365 versus baseline."}
• {"endpoint_text":"- Achieving revised CRISS-75 scores at study day 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Change in revised CRISS-75 score at study days 90, 180, 270 and 365 versus baseline."}
• {"endpoint_text":"- Achieving revised CRISS-100 scores at study day 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Change in revised CRISS-100 score at study days 90, 180, 270 and 365 versus baseline."}
• {"endpoint_text":"- mRSS at study day 36, 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Modified Rodnan skin score (mRSS) measured at study days 36, 90, 180, 270 and 365 versus baseline."}
• {"endpoint_text":"- Pulmonary function test results (FVC and DLCO % predicted) at study day 180 and 365 compared to baseline.","definition_or_measurement_approach":"Pulmonary function tests: FVC and DLCO (% predicted) at study day 180 and 365 versus baseline."}
• {"endpoint_text":"- HRCT quantification at at study day 180 and 365 compared to baseline.","definition_or_measurement_approach":"High-resolution CT quantification compared at study day 180 and 365 versus baseline."}
• {"endpoint_text":"- Other patient reported measures of function and Quality of Life questionnaires: SHAQ, SF-36, UCLA SCTC GIT 2.0 and EQ5d at study day 36, 90, 180, 270 and 365 compared to baseline.","definition_or_measurement_approach":"Patient-reported outcome measures (SHAQ, SF-36, UCLA SCTC GIT 2.0, EQ-5D) at specified study days versus baseline."}
• {"endpoint_text":"- Organ worsening as defined in Step 1 of the revised CRISS- 25 score during 365 days after treatment start.","definition_or_measurement_approach":"Occurrence of organ worsening as defined by Step 1 of the revised CRISS-25 within 365 days after treatment start."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

233

Number Of Sites

1

Number Of Participants

13

Primary sponsor

Full Name

Philikos B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands