Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
Hemolytic Paroxysmal Nocturnal Hemoglobinuria, Eculizumab, PNH, Japan
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.
Interventions
BIOLOGICALEculizumab
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Lactate Dehydrogenase | Baseline, Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Free Hemoglobin | Baseline, Week 12 | — |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score | Baseline, 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. |
| Change From Baseline in Lactate Dehydrogenase (LDH) Area Under the Curve (AUC) | Baseline to Week 12 | — |
| Number of Units of Packed Red Blood Cells (pRBCs) Transfused | 12 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 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. |
| Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count | Baseline, Week 12 | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab Eculizumab 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 | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 12.39 |
| Race/Ethnicity, Customized Japanese | 29 Participants |
| Region of Enrollment Japan | 29 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 28 / 29 |
| serious Total, serious adverse events | 1 / 29 |
Outcome results
Primary
Change From Baseline in Lactate Dehydrogenase
Time frame: Baseline, Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Lactate Dehydrogenase | Baseline | 1845.1 Units/Liter | Standard Error 115.34 |
| Eculizumab | Change From Baseline in Lactate Dehydrogenase | Week 12 | 398.7 Units/Liter | Standard Error 99.15 |
| Eculizumab | Change From Baseline in Lactate Dehydrogenase | Change from Baseline at Week 12 | -1446.4 Units/Liter | Standard Error 138.68 |
p-value: <0.0001Sign test
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score (Global Health Status)
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.
Time frame: Baseline, Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score (Global Health Status) | 8.9 units on a scale | Standard Error 6.39 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score
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.
Time frame: Baseline, Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score | Baseline | 38.5 units on a scale | Standard Error 1.88 |
| Eculizumab | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score | Change from Baseline at Week 12 | 4.1 units on a scale | Standard Error 2.25 |
Secondary
Change From Baseline in Lactate Dehydrogenase (LDH) Area Under the Curve (AUC)
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in Lactate Dehydrogenase (LDH) Area Under the Curve (AUC) | -113540.5 U/L x Day | Standard Error 10539.33 |
Secondary
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count
Time frame: Baseline, Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count | Baseline | 1.3 cells x 10^12/L | Standard Error 0.14 |
| Eculizumab | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count | Week 12 | 1.8 cells x 10^12/L | Standard Error 0.19 |
| Eculizumab | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count | Change from Baseline at Week 12 | 0.5 cells x 10^12/L | Standard Error 0.1 |
Secondary
Change From Baseline in Plasma Free Hemoglobin
Time frame: Baseline, Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Plasma Free Hemoglobin | Baseline | 22.6 mg/dL | Standard Error 2.61 |
| Eculizumab | Change From Baseline in Plasma Free Hemoglobin | Change from Baseline at Week 12 | -19.8 mg/dL | Standard Error 2.71 |
Secondary
Number of Units of Packed Red Blood Cells (pRBCs) Transfused
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
Time frame: 12 weeks pre-treatment, baseline, 12 weeks post-treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Number of Units of Packed Red Blood Cells (pRBCs) Transfused | 12 Weeks Pre-Dose | 5.2 Units | Standard Error 1.04 |
| Eculizumab | Number of Units of Packed Red Blood Cells (pRBCs) Transfused | 12 Weeks Post-Dose | 1.5 Units | Standard Error 0.67 |
| Eculizumab | Number of Units of Packed Red Blood Cells (pRBCs) Transfused | Difference Post - Pre | -3.7 Units | Standard Error 1.12 |