The goal of this clinical trial is to learn if drug SLN12140 works to treat Complement Inhibitor-Naïve Subjects with Paroxysmal Nocturnal Hemoglobinuria in adults. It will also learn about the safety, pharmacokinetic characteristics, and dosing of drug SLN12140. The study is divided into four phases: screening period, core treatment period, extended dosing period, and follow-up period, and includes two cohorts (Cohorts 1-2), with each cohort enrolling at least 5 treatment-naïve adult PNH subjects for complement inhibitor therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
5 participants will receive SLN12140 100mg QW for 4 weeks, then 300mg QW for 8 weeks, then 200mg QW for 52 weeks. 5 participants will receive SLN12140 200mg QW for 4 weeks, then 600mg Q4W for 60 weeks
During the 12-week treatment period, the proportion of participants whose Lactate Dehydrogenase (LDH) decreased by 60% or more from baseline or whose LDH was below the upper limit
To assess efficacy of SLN12140 in participants with PNH
Time frame: 12weeks after baseline
Percentage change of LDH from baseline
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
Proportion of participants achieving hemolysis control (LDH ≤ 1.5×ULN)
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
Change in hemoglobin (Hb) levels from baseline
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through week 64
The proportion of participants whose hemoglobin (Hb) increased by ≥2 g/dL from baseline and who avoided blood transfusion
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
Proportion of participants who avoided blood transfusion
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
Incidence(%) of Breakthrough Hemolysis (BTH)
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Changes from baseline in intravascular and extravascular hemolysis indicators (including but not limited to reticulocytes, bilirubin, red blood cell count, platelet count, ferritin, etc.)
To assess the efficacy of SLN12140 in participants with PNH
Time frame: baseline through week 64
Changes in thrombus formation risk markers from baseline (including but not limited to fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin D-dimer, etc.);
To assess the efficacy of SLN12140 in participants with PNH
Time frame: Baseline through week 64
Change in functional assessment of Functional Assessment of Chronic Illness Therapy (FACIT)
To assess the efficacy of SLN12140 in participants with PNH. FACIT is a 40-item measure that assesses self-reported fatigue and its impact upon daily activities and function to assess the Impact of SLN12140 on Treatment-Related Outcomes. The minimum value is 0 and maximum value is 52, and higher scores mean a worse outcome.
Time frame: Baseline through Week 64
Number(%) of participants with Adverse Events (AEs) , Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
To assess the safety and tolerability of SLN12140 in participants with PNH
Time frame: Baseline through Week 64
Pharmacokinetics (PK)parameters of SLN12140: Area Under The Plasma Concentration-time Curve
To characterize the pharmacokinetics of SLN12140 in participants with PNH
Time frame: Baseline through week 64 (predose and postdose)
Immunegenicity in Paraxysmal Nocturnal Hemoglobinuria
Determine anti-drug antibody titers
Time frame: Baseline through Week 64
PK: Maximum Plasma Concentration (Cmax)
To characterize the pharmacokinetics of SLN12140 in participants with PNH
Time frame: Baseline through week 64( predose and postdose)
PK: Time To Maximum Concentration (Tmax)
To characterize the pharmacokinetics of SLN12140 in participants with PNH
Time frame: Baseline through week 64( predose and postdose)
Complement Alternative Pathway (AP) Functional Activity
Serum AP functional activity was measured by the Wieslab functional immunoassay method.
Time frame: Baseline through week 64( predose and post dose)
Complement FP
Plasma FP was measured by enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline through week 64(predose and postdose)