Paroxysmal Nocturnal Hemoglobinuria, PNH
Conditions
Keywords
Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab
Brief summary
The primary objective of this study is to evaluate the efficacy of ravulizumab in adult participants with PNH.
Interventions
DRUGRavulizumab
Ravulizumab will be administered by intravenous (IV) infusion.
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
* Adult C5 inhibitor naive PNH patients (age\>=18), which is confirmed by flow cytometry evaluation. * Must be vaccinated againast N meningitidis.
Exclusion criteria
* Meningitidis infection or unresolved meningococcal disease * History of bone marrow transplantation * Other significant systemic diseases that might have impact on efficacy and safety assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Lactate Dehydrogenase (LDH) From Baseline to Day 183 (Week 26) | Baseline, Day 183 (Week 26) | LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicated reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first dose of study drug. The percent change in LDH was analyzed using a mixed-effect model for repeated measures (MMRM) with the fixed categorical effect of visit, fixed continuous effect of the LDH baseline value as covariates, and participant as random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving LDH <1.5 * Upper Limit of Normal (ULN) at Day 183 (Week 26) | Day 183 (Week 26) | LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicated reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first dose of study drug. |
| Percentage of Participants Achieving Transfusion Avoidance Through Day 183 (Week 26) | Day 183 (Week 26) | Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 grams (g)/deciliter (dL) with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through Day 183. |
| Percentage of Participants Experiencing Breakthrough Hemolysis Through Day 183 (Week 26) | Day 183 (Week 26) | Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia \[hemoglobin \<10 g/dL\], major adverse vascular event \[including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the ULN. |
| Change in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score From Baseline to Day 183 (Week 26) | Baseline, Day 183 (Week 26) | 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. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with a higher score indicating better quality of life. Analysis was using a mixed-effect model for repeated measures (MMRM) with the fixed categorical effect of visit, fixed continuous effect of the baseline value of FACIT-Fatigue score as covariates, and participant as random effect. |
| Change in Hemoglobin (Hgb) From Baseline to Day 183 (Week 26) | Baseline, Day 183 (Week 26) | Analysis was performed using MMRM with the fixed categorical effect of visit, fixed continuous effect of the Hgb baseline value as covariates, and participant as random effect. |
Countries
China
Participant flow
Pre-assignment details
The study included a 26-week Primary Treatment Period, and an additional 32-week Extension Treatment Period. The results for the Primary Treatment Period have been reported. Final analysis data will be reported after completion of the 32-week Extension Treatment Period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 18 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 | 3 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 16 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
None listed