Title
A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH
An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
Phase
Phase 1Lead Sponsor
Apellis Pharmaceuticals, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Paroxysmal Nocturnal Hemoglobinuria (PNH)Intervention/Treatment
pegcetacoplan ...Study Participants
9This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.
Complement (C3) Inhibitor
Inclusion Criteria: Male or Female At least 18 years of age Weigh >55 kg Diagnosed with PNH On treatment with eculizumab (Soliris®) for at least 3 months Hb < 10 g/dL at screening OR have received at least one transfusion within 12 months prior to screening Platelet count of >30,000/mm3 Absolute neutrophil count > 500/mm3 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 (see below) Males with female partners of child bearing potential must agree to use protocol defined methods of contraception (see below) and agree to refrain from donating sperm for the duration of the study Willing and able to give informed consent Exclusion Criteria: Active bacterial infection Known infection with hepatitis B, C or HIV Hereditary complement deficiency History of bone marrow transplantation Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days Evidence of QTcF prolongation defined as > 450 ms for males and > 470 ms for females at screening Creatinine clearance (CrCl) < 50 mL/min (Cockcroft-Gault formula) at screening Breast-feeding women History of meningococcal disease No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.
| Event Type | Organ System | Event Term | Cohort 1 Single-dose Phase | Cohort 2 Single-dose Phase | Cohort 1 Multiple-dose Phase | Cohort 2 Multiple-dose Phase | Cohort 3 Multiple-dose Phase | Cohort 4 Multiple-dose Phase |
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TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.
Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.
