PEGASUS: A Phase 3 study to evaluate the efficacy and safety of APL-2 in patients with PNH

The purpose of this study is to establish the efficacy and safety of APL-2 compared to eculizumab in patients with PNH who continue to have Hb levels <10.5 g/dL despite treatment with eculizumab (Soliris®).

 

This study will enroll approximately 70 subjects around the globe to compare APL-2 to eculizumab treatment. All subjects who qualify will receive APL-2, an investigational product that inhibits the complement system at the level of C3.

 

Status: Recruiting
Associated Drug(s): Eculizumab (Soliris®)
Phase: Phase 3
Gender: Female, Male
Age Group: 18 years and older

 

Inclusion Criteria:

 

  • At least 18 years of age, with primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
  • On treatment with stable dose of eculizumab for at least 3 months
  • Hemoglobin <10.5 g/dL
  • Absolute reticulocyte count >1.0x ULN
  • Platelet count of >50,000/mm3
  • Absolute neutrophil count >500/mm3
  • BMI <= 40 kg/m2
  • Have or are willing to receive vaccination against Neisseria meningitides (types A, C, W, Y and B), Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib)
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
  • Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
  • Willing and able to give informed consent
  • Willing and able to self-administer APL-2 (administration by caregiver will be allowed)

 

Exclusion Criteria:

 

  • Active bacterial infection that has not resolved within 1 week before starting study drug
  • Receiving unstable doses of iron, folic acid, vitamin B12 or EPO within 4 weeks before study start
  • Hereditary complement deficiency
  • History of bone marrow transplantation
  • Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
  • Currently breast-feeding women
  • History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
  • Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
  • QTcF > 470 ms or PR > 280 ms
  • Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
  • Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine