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Safety and Efficacy Study of Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients

Phase 2
Completed
Conditions
Paroxysmal Nocturnal Hemoglobinuria
Interventions
Biological: Eculizumab
Registration Number
NCT01192399
Lead Sponsor
Alexion Pharmaceuticals, Inc.
Brief Summary

A study to assess the safety and efficacy of eculizumab in Japanese patients with hemolytic PNH.

Detailed Description

The objective of this study was to assess the safety and efficacy of eculizumab in Japanese patients with hemolytic PNH. In addition, the pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab in Japanese patients were assessed and compared to that of non-Japanese patients who had participated earlier studies of eculizumab treatment in hemolytic PNH.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
Inclusion Criteria
  • Japanese individuals at least 12 years of age
  • Diagnosis of PNH > 6 months
  • At least one transfusion in the past 2 years for anemia or anemia-related symptoms
  • LDH level ≥ 1.5 x upper limit of normal within 12 weeks
  • Presence of a glycosylphosphatidylinositol (GPI)-deficient red blood cell (RBC) clone (type III cells) by flow cytometry of ≥10%
  • Negative serum pregnancy test for women of child-bearing potential
Exclusion Criteria
  • Platelet count < 30,000/µL
  • Absolute neutrophil count ≤ 500/µL
  • Known or suspected hereditary complement deficiency
  • History of hematopoietic stem cell transplant
  • History of meningococcal disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EculizumabEculizumabEculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Lactate DehydrogenaseBaseline, Week 12
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Plasma Free HemoglobinBaseline, Week 12
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) CountBaseline, Week 12
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total ScoreBaseline, Week 12

The FACIT-Fatigue scale, Version 4.0, is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Patients score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.

Number of Units of Packed Red Blood Cells (pRBCs) Transfused12 weeks pre-treatment, baseline, 12 weeks post-treatment

Comparison of number of units of pRBCs transfused in the 12 weeks prior to the first dose of eculizumab, and between baseline and 12 weeks after the first dose of eculizumab

Change From Baseline in Lactate Dehydrogenase (LDH) Area Under the Curve (AUC)Baseline to Week 12
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score (Global Health Status)Baseline, Week 12

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. For global health status, a high score represents a high quality of life.

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