Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
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.
Interventions
DRUGSLN12140
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
Sponsors
Linno Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult complement inhibitor naïve PNH patients (age\>=18), which is confirmed by flow cytometry evaluation * Must be vaccinated against meningococcal vaccine and pneumococcal vaccine
Exclusion criteria
* Significant bone marrow failure * Meningitidis infection or unresolved meningococcal disease * Other significant systemic diseases that might have impact on efficacy and safety assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 12weeks after baseline | To assess efficacy of SLN12140 in participants with PNH |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change of LDH from baseline | Baseline through Week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Proportion of participants achieving hemolysis control (LDH ≤ 1.5×ULN) | Baseline through Week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Change in hemoglobin (Hb) levels from baseline | Baseline through week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| The proportion of participants whose hemoglobin (Hb) increased by ≥2 g/dL from baseline and who avoided blood transfusion | Baseline through Week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Proportion of participants who avoided blood transfusion | Baseline through Week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Incidence(%) of Breakthrough Hemolysis (BTH) | Baseline through Week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Changes from baseline in intravascular and extravascular hemolysis indicators (including but not limited to reticulocytes, bilirubin, red blood cell count, platelet count, ferritin, etc.) | baseline through week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| 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.); | Baseline through week 64 | To assess the efficacy of SLN12140 in participants with PNH |
| Change in functional assessment of Functional Assessment of Chronic Illness Therapy (FACIT) | Baseline through Week 64 | 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. |
| Number(%) of participants with Adverse Events (AEs) , Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline through Week 64 | To assess the safety and tolerability of SLN12140 in participants with PNH |
| Pharmacokinetics (PK)parameters of SLN12140: Area Under The Plasma Concentration-time Curve | Baseline through week 64 (predose and postdose) | To characterize the pharmacokinetics of SLN12140 in participants with PNH |
| Immunegenicity in Paraxysmal Nocturnal Hemoglobinuria | Baseline through Week 64 | Determine anti-drug antibody titers |
| PK: Maximum Plasma Concentration (Cmax) | Baseline through week 64( predose and postdose) | To characterize the pharmacokinetics of SLN12140 in participants with PNH |
| PK: Time To Maximum Concentration (Tmax) | Baseline through week 64( predose and postdose) | To characterize the pharmacokinetics of SLN12140 in participants with PNH |
| Complement FP | Baseline through week 64(predose and postdose) | Plasma FP was measured by enzyme-linked immunosorbent assay (ELISA). |
| Complement Alternative Pathway (AP) Functional Activity | Baseline through week 64( predose and post dose) | Serum AP functional activity was measured by the Wieslab functional immunoassay method. |
Contacts
CONTACTHong Yan Tong, Professor
CONTACTFeng Kui Zhang, Professor
Outcome results
None listed