Details

Details

Title A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

IRB ALEX1Z16

CC 17-089

Hospital Main Campus

Phase Phase 3

Disease Paroxysmal Nocturnal Hemoglobinuria (PNH)

Drug ALXN1210 , Eculizumab

Description

Description

Primary Objective
  • To assess the noninferiority of ALXN1210 compared to eculizumab in adult patients with PNH who have never been treated with a complement inhibitor.
Secondary Objectives
  • To characterize the safety and tolerability of ALXN1210 in this patient population
  • To evaluate the efficacy of ALXN1210 by additional efficacy measures
  • To characterize the pharmacokinetics/pharmacodynamics (PK/PD) and immunogenicity of ALXN1210
  • To evaluate the long-term safety and efficacy of ALXN1210
  • To evaluate the safety and efficacy in patients who switch from eculizumab to ALXN1210 in the Extension Period
Inclusion Criteria

Inclusion Criteria

  1. Male or female, 18 years of age or older at the time of consent.
  2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation (Borowitz 2010) of RBCs and white blood cells (WBCs), with granulocyte or monocyte clone size of ≥ 5%.
  3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin < 10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH.
  4. LDH level ≥ 1.5 x ULN at Screening.
  5. To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
  6. Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance (Section 9.11) for avoiding pregnancy while on treatment and for 8 months after last dose of study drug.
  7. Patients must be willing and able to give written informed consent and to comply with all study visits and procedures, including the use of any data collection device(s) to directly record patient data.
Exclusion Criteria

Exclusion Criteria

  1. Current or previous treatment with a complement inhibitor.
  2. Platelet count < 30,000/mm3 (30 x 109/L) at Screening.
  3. Absolute neutrophil count < 500/μL (0.5 x 109/L) at Screening.
  4. History of bone marrow transplantation.
  5. Body weight < 40 kg at Screening.
  6. History of N. meningitidis infection.
  7. History of unexplained, recurrent infection.
  8. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on Day 1.
  9. Presence of fever ≥ 38oC (100.4oF) within 7 days prior to study drug administration on Day 1.
  10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
  11. Immunized with a live-attenuated vaccine 1 month prior to study drug administration on Day 1.
  12. History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
  13. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active hepatitis) that, in the opinion of the Investigator or Sponsor, precludes the patient's participation in an investigational clinical trial.
  14. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH) that would make them unlikely to tolerate the requirements of the protocol (eg, transfusion guidelines).
  15. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
  16. History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
  17. Females who plan to become pregnant or are currently pregnant or breastfeeding.
  18. Females who have a positive pregnancy test result at Screening or on Day 1.
  19. Participation in another interventional treatment study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.
  20. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of Screening.
  21. Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the patient's full participation in the study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of the study.