Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
paroxysmal nocturnal hemoglobinuria, PNH
Brief summary
This is a Phase 3b, single-arm, open-label, multicenter study to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of eculizumab in adult participants with paraxysmal noturnal hemoglobinuria (PNH) in China.
Detailed description
This is a Phase 3b, single-arm, open-label, multicenter study to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of eculizumab in adult participants with PNH in China who previously have not been treated with complement inhibitors. Approximately 25 eligible participants in China will be enrolled.
Interventions
DRUGEculizumab
Participants will receive 600 milligrams (mg) once a week on Day 1, 8, 15, and 22 followed by 900 mg every 2 weeks from Day 29 to Day 435.
Sponsors
Alexion Pharmaceuticals, Inc.
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult C5 inhibitor naïve PNH patients (age\>=18), which is confirmed by flow cytometry evaluation * Must be vaccinated against N meningitidis
Exclusion criteria
* Meningitidis infection or unresolved meningococcal disease * Significant bone marrow failure * Other significant systemic diseases that might have impact on efficacy and safety assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in LDH at Week 12 | Baseline, Week 12 | Blood samples were collected for measurement of serum LDH at specified timepoints. Statistical analysis was performed using a mixed model for repeated measures (MMRM), including the percentage change from baseline of LDH at the scheduled visits from Week 1 to Week 12 as the dependent variable, with the fixed categorical effect of visit, fixed continuous effect of LDH baseline value as covariates, and participant as random effect. Assessed at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 weeks, Week 12 reported. A decrease indicated a reduction in disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline through Week 64 | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with the study intervention. A TEAE was any AE that started during or after the first infusion of the study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Serum Concentration of Eculizumab | Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449 | Blood samples were collected for measurement of serum concentrations of eculizumab at specified timepoints. No study intervention administered on Day 449. Results reported as micrograms/milliliter (ug/mL). |
| Change From Baseline in Serum Free Complement 5 (C5) Concentration | Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449 | Blood samples were collected for measurement of serum concentration of free C5 at specified timepoints. No study intervention administered on Day 449. A decrease indicated a reduction in disease activity. |
| Change From Baseline in Serum Total C5 Concentration | Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449 | Blood samples were collected for measurement of serum concentration of total C5 at specified timepoints. No study intervention administered on Day 449. A decrease indicated a reduction in disease activity. |
| Number of Participants With Treatment-emergent Antidrug Antibodies (ADAs) to Eculizumab | Baseline through Week 64 | Blood samples were collected for measurement of treatment-emergent ADAs to eculizumab at specified timepoints. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | Baseline, Week 12 | 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. The FACIT-Fatigue scale is a collection of quality of life (QoL) questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores were calculated as the sum from all 13 items and ranged from 0 to 52, with higher scores indicating an increased QoL. Analysis was performed using a MMRM, including FACIT-Fatigue score change from baseline values at the scheduled visits from Week 1 to Week 12 as the dependent variable, with the fixed categorical effect of study visit, fixed continuous effect of baseline value of FACIT-Fatigue, and participant as random effect. Assessed at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 weeks, Week 12 reported. |
| Percentage of Participants With Breakthrough Hemolysis | Baseline through Week 12 | Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 grams/deciliter\], major adverse vascular event \[including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times (\*) upper limit of normal (ULN), after prior LDH reduction to \<1.5\* ULN on therapy. |
| Percentage of Participants Achieving LDH Normalization | Baseline through Week 12 | Blood samples were collected for measurement of LDH at specified timepoints. LDH normalization was defined as LDH ≤ULN. |
| Percentage of Participants Achieving Transfusion Avoidance | Baseline through Week 12 | Transfusion avoidance was defined as remaining transfusion free (that is, had not received any transfusion) and did not require transfusion as per protocol. |
| Percentage of Participants With LDH ≤1.5* ULN at Week 12 | Baseline through Week 12 | Blood samples were collected for measurement of LDH at specified timepoints. |
Countries
China
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 13.4 |
| Baseline Lactate Dehydrogenase (LDH) | 1657.50 U/L STANDARD_DEVIATION 575.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 25 |
| other Total, other adverse events | 21 / 25 |
| serious Total, serious adverse events | 9 / 25 |
Outcome results
None listed