Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 20.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Interventions
Product Code: APL-2
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Not yet assigned
CAS Number: 2019171-69-6
Current Sponsor code: APL-2
Concentration unit: mg/ml milligram(
Sponsors
Apellis Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years old (inclusive) 2. Diagnosed with PNH (WBC clone >10%) 3. Lactose dehydrogenase =2 times the upper limit of normal 4. Screening Ferritin = normal and Total Iron Binding Capacity (TIBC) = LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study (see Protocol Section 8.4.4) 5. Last transfusion within 12 months prior to screening 6. Platelet count of >30,000/mm3 at the screening visit 7. Absolute neutrophil count >500/ mm3 at the screening visit 8. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study 9. Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study 10. Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits 11. Willing and able to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Prior eculizumab (Soliris®) treatment 2. Active bacterial infection 3. Hereditary complement deficiency 4. History of bone marrow transplantation 5. Concurrent SAA, defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or antithymocyte globulin 6. Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days 7. Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening 8. Breast-feeding women 9. History of meningococcal disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of the study are to assess safety, tolerability, preliminary efficacy and PK of multiple SC doses of APL-2 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab (Soliris)® in the past.;Secondary Objective: An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of APL-2 when administered to PNH subjects.;Primary end point(s): Primary Safety Endpoint: The primary safety endpoints of the study are the number and severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. Primary Efficacy Endpoints: • Change from baseline in Lactate dehydrogenase (LD) • Change from baseline in Haptoglobin • Change from baseline in Hemoglobin (Hb);Timepoint(s) of evaluation of this end point: Primary Safety Endpoint: after dosing on Day 1 and up to 30 days after the last dose of study medication. Primary Efficacy Endpoints: Change from baseline in LD, Haptoglobin and Hb: will be calculated for each post dose assessment. The baseline: the last measurement prior to the start of dosing. Please refer to STUDY FLOW CHART in the Protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • APL-2 plasma concentrations (and pharmacokinetic (PK) parameters as appropriate) • Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale score • Change from baseline in reticulocyte count • Change from baseline in total bilirubin • Number of red blood cell (RBC) transfusions per month • Change from baseline in Linear Analog Scale Assessment (LASA) for Quality of Life Baseline will be taken as the last measurement prior to the start of dosing. For transfusions baseline will be taken from the 12 month transfusion history. Exploratory PD markers include: • Complement (CH50, AP50, and C3) levels • C3 deposition on RBC cells • Clonal distribution of PNH RBCs ;Timepoint(s) of evaluation of this end point: • APL-2 plasma concentrations (and PK parameters): Plasma concentrations of APL-2 will be determined from multiple samples taken between Day 1 and the Exit Visit. • Change from baseline in FACIT Fatigue Scale score: Please refer to STUDY FLOW CHART in the Protocol • Change from baseline in reticulocyte count: Please refer to STUDY FLOW CHART in the Protocol • Change from baseline in total bilirubin: Please refer to STUDY FLOW CHART in the Protocol • Number of RBC transfusions per month: Please refer to STUDY FLOW CHART in the Protocol • Change from baseline in Linear Analog Scale Assessment for Quality of Life: Please refer to STUDY FLOW CHART in the Protocol Baseline: the last measurement prior to the start of dosing. Baseline for transfusions: from the 12 M transfusion history | — |
Countries
Bulgaria, Greece, Poland, Romania, Serbia
Contacts
Public ContactHead of Clinical Operations
Apellis Pharmaceuticals
Outcome results
None listed