Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. Pegcetacoplan (APL-2) in PNH Subjects.
Condition: Paroxysmal Nocturnal Hemoglobinuria
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: Pegcetacoplan
Intervention description: Complement (C3) Inhibitor
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PNH; Paroxysmal Nocturnal Hemoglobinuria; Complement inhibitor; Anemia; Hemoglobinuria; Hemolysis; Hematologic diseases; Extravascular hemolysis (EVH); Intravascular hemolysis (IVH); C3 inhibitor

Summary:

      The objectives of the study are to assess the safety, tolerability, preliminary efficacy and
      PK of multiple subcutaneous (SC) doses of pegcetacoplan in subjects with paroxysmal nocturnal
      hemoglobinuria (PNH) who have not received treatment with eculizumab in the past.

      An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC
      doses of pegcetacoplan when administered to PNH patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female

          -  At least 18 years old (inclusive)

          -  Weigh >55 kg and have a body mass index (BMI) ≤38.0 kg/m2

          -  Diagnosed with PNH (white blood cell (WBC) clone >10%)

          -  Lactose dehydrogenase (LD) ≥2 times the upper limit of normal

          -  Last transfusion within 12 months prior to screening

          -  Platelet count of >30,000/mm3

          -  Absolute neutrophil count >cells/500 µL

          -  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

          -  Males must agree to use protocol defined methods of contraception and agree to refrain
             from donating sperm for the duration of the study

          -  Able to provide documentary evidence of Neisseria meningitidis, Pneumococcal conjugate
             vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23) and
             Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 dosing,
             OR willing to receive vaccinations against Neisseria meningitidis at least two weeks
             prior to dosing on Day 1 with a booster on Day 57, and PCV13 and Hib vaccines at least
             two weeks prior to dosing on Day 1.

          -  Willing and able to give informed consent

        Exclusion Criteria:

          -  Prior eculizumab (Soliris)® treatment

          -  Active bacterial infection

          -  Known infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)

          -  Hereditary complement deficiency

          -  History of bone marrow transplantation

          -  Concurrent severe aplastic anemia (SAA), defined as currently receiving
             immunosuppressive therapy for SAA including but not limited to cyclosporin A,
             tacrolimus, mycophenolate mofetil or anti-thymocyte globulin.

          -  Participation in any other investigational drug trial or exposure to another
             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