Paroxysmal Hemoglobinuria, Nocturnal
Conditions
Keywords
transfusion dependent, paroxysmal nocturnal hemoglobinuria, hemolytic
Brief summary
The purpose of this study is to evaluate the long-term safety of eculizumab in patients with transfusion dependent hemolytic PNH.
Detailed description
An open-label extension study to evaluate long-term safety of eculizumab in PNH patients who had completed the TRIUMPH (C04-001), SHEPHERD (C04-002), and X03-001 studies.
Interventions
DRUGeculizumab
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have fully completed the TRIUMPH, SHEPHERD, or X03-001 studies * TRIUMPH patients who have discontinued receiving investigational drug prior to the last visit of the study due to lack of efficacy or exacerbation of symptoms of PNH and have completed all monthly safety and efficacy procedures * Patient must be willing and able to give written informed consent * Patient must avoid conception during the trial
Exclusion criteria
* Patients who have terminated early from the SHEPHERD or X03-001 studies * Patients who have terminated early from the TRIUMPH study due to an adverse event * Female who is pregnant, breast feeding, or intending to conceive during the course of the study * Any condition that could increase the patient's risk by participating in the study or could confound the outcome of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-emergent Adverse Events | From time of consent to a maximum of 2.5 years of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemolysis as Measured by Change From Baseline in LDH Area Under the Curve | From time of first infusion through 24 months of study treatment | — |
| Quality of Life as Measured by FACIT-Fatigue Scale Change From Baseline | From time of first infusion through 24 months of study treatment | The FACIT-Fatigue scale 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. |
| Incidence of Thrombosis After Eculizumab Infusion | From time of first ever dose through last dose (up to 24 months of study treatment) | Thrombosis was defined as occurrence of major adverse vascular events |
Countries
Australia, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks | 187 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 3 |
| Overall Study | patient non-compliance | 1 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 14.1 |
| Race/Ethnicity, Customized Asian | 6 Participants |
| Race/Ethnicity, Customized Black | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 168 Participants |
| Race/Ethnicity, Customized Other | 6 Participants |
| Sex: Female, Male Female | 101 Participants |
| Sex: Female, Male Male | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 187 |
| other Total, other adverse events | 180 / 187 |
| serious Total, serious adverse events | 57 / 187 |
Outcome results
Primary
Incidence of Treatment-emergent Adverse Events
Time frame: From time of consent to a maximum of 2.5 years of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Incidence of Treatment-emergent Adverse Events | 182 Participants |
Secondary
Hemolysis as Measured by Change From Baseline in LDH Area Under the Curve
Time frame: From time of first infusion through 24 months of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Hemolysis as Measured by Change From Baseline in LDH Area Under the Curve | -365185.8 U/L x Day | Standard Deviation 210407.1 |
Secondary
Incidence of Thrombosis After Eculizumab Infusion
Thrombosis was defined as occurrence of major adverse vascular events
Time frame: From time of first ever dose through last dose (up to 24 months of study treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab | Incidence of Thrombosis After Eculizumab Infusion | Prior to first eculizumab dose | 7.82 Number of events per 100 patient-years |
| Eculizumab | Incidence of Thrombosis After Eculizumab Infusion | From first dose of eculizumab through last dose | 1.99 Number of events per 100 patient-years |
Secondary
Quality of Life as Measured by FACIT-Fatigue Scale Change From Baseline
The FACIT-Fatigue scale 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: From time of first infusion through 24 months of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Quality of Life as Measured by FACIT-Fatigue Scale Change From Baseline | 9.24 units on a scale | Standard Deviation 12.42 |