Clinical Trial: A Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Pa

Brief Summary: The primary purpose of this study is to evaluate the safety, tolerability and efficacy of multiple IV doses of ALXN1210 administered to complement inhibitor treatment-naïve patients with PNH.

Detailed Summary:
Sponsor: Alexion Pharmaceuticals

Current Primary Outcome:

  • To evaluate the safety as measured by change in the number of treatment-emergent and related adverse events as assessed by CTCAE (v4.03). [ Time Frame: Treatment Period (36 weeks) and Follow-up Period (week 36 to week 144) ]
    Safety will be assessed as the reported incidence, number and severity of AEs, SAEs or AE-related discontinuation from the study, change from baseline in vital signs (body weight, blood pressure, heart rate), out of reference range laboratory results (serum chemistries including renal function, hematology, coagulation) and ECG assessments through week 36.
  • Efficacy as measured by the percentage change in lactate dehydrogenase or LDH levels from baseline to Day 253 during treatment with ALXN1210. [ Time Frame: 36 weeks ]
    Percentage change in serum LDH levels (IU/L) from Baseline to week 36.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to maximal concentration of ALXN1210 in blood (tmax) [ Time Frame: 36 weeks ]
  • Area Under the plasma concentration versus time Curve (AUC) of ALXN1210 [ Time Frame: 36 weeks ]
  • Peak Plasma Concentration (Cmax) of ALXN1210 [ Time Frame: 36 weeks ]
  • ALXN1210 elimination half-life (t1/2) in blood [ Time Frame: 36 weeks ]
  • Change from baseline in concentration of complement factor 5 (C5) [ Time Frame: Treatment Period (36 weeks) and Follow-up Period (week 36 to week 144) ]
    Pharmacodynamic (PD) activity of ALXN1210 will be assessed by changes from baseline in complement related and hematologic parameters
  • Change from baseline in serum levels of terminal complement activity [ Time Frame: Treatment Period (36 weeks) and Follow-up Period (week 36 to week 144) ]
    Pharmacodynamic (PD) activity of ALXN1210 will be assessed by changes from baseline in complement related and hematologic parameters
  • Development of antibodies against ALXN1210 [ Time Frame: Up to 144 weeks ]
    Assessment of anti-ALXN1210 antibodies (whether detectable, and titers if positive) from baseline through end of study [Time Frame: Treatment Period through Follow-up Period (week 36 to week 144)]


Original Secondary Outcome: Same as current

Information By: Alexion Pharmaceuticals

Dates:
Date Received: November 11, 2015
Date Started: November 2015
Date Completion: December 2018
Last Updated: March 17, 2017
Last Verified: March 2017