A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
Condition: PNH
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: Pegcetacoplan
Intervention description: Complement (C3) Inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
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:

      This is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not
      received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for
      evaluation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years old (inclusive)

          -  Diagnosed with PNH (white blood cell (WBC) clone >10%)

          -  Lactose dehydrogenase (LD) ≥2 times the upper limit of normal

          -  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

          -  Last transfusion within 12 months prior to screening

          -  Platelet count of >30,000/mm3 at the screening visit

          -  Absolute neutrophil count >500/ mm3 at the screening visit

          -  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

          -  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 pegcetacoplan. Unless
             documented evidence exists that subjects are non-responders to vaccination as
             evidenced by titers or display titer levels within acceptable local limits

          -  Willing and able to give informed consent

        Exclusion Criteria:

          -  Prior eculizumab (Soliris®) treatment

          -  Active bacterial infection

          -  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

          -  Breast-feeding women

          -  History of meningococcal disease