Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Keywords
paroxysmal nocturnal hemoglobinuria, PNH, extravascular hemolysis, EVH, factor D inhibitor, complement, C5 inhibitor, danicopan
Brief summary
The study will evaluate the efficacy and safety of the oral Factor D (FD) inhibitor ALXN2050 (ACH-0145228) monotherapy in patients with PNH that are treatment naïve, or patients currently treated with eculizumab who still experience anemia and reticulocytosis, or patients currently treated with ALXN2040 (danicopan) as monotherapy. After signing consent, participants will have periodic visits through Week 12, at which time the primary endpoint and key secondary assessments will be analyzed. Participants will continue on treatment past 12 weeks into a long-term extension portion of the trial.
Detailed description
Experimental: Open-label ALXN2050 Monotherapy orally Group 1: Patients with PNH who are treatment naïve Group 2: Patients with PNH who have received complement component 5 (C5) inhibition with eculizumab for at least 6 months, who continue to experience anemia and reticulocytes above the upper limit of normal (ULN) who will switch to ALXN2050 monotherapy Group 3: Patients with PNH receiving danicopan monotherapy in study ACH471-103 will switch to ALXN2050 monotherapy After signing the informed consent form, participants will enter the screening period. During the Screening Period, eligibility and screening assessments will be performed. Screening assessments may be spread over more than one visit if necessary. At the baseline visit, screened participants who continue to meet eligibility criteria will enter the Treatment Period. The treatment phase will be followed by a long-term extension phase, where ALXN2050 will continue to be administered. Blood will be collected to assess the efficacy endpoints, such as, change in hemoglobin (Hgb), lactate dehydrogenase (LDH), and other measures of hemolysis. Safety and transfusion requirements will also be assessed. Participants will continue on treatment past 12 weeks in a long-term extension portion of the trial.
Interventions
DRUGALXN2050
Oral FD inhibitor
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of PNH. 2. Male or female, ≥ 18 years of age Eligibility Criteria: Eligibility Criteria Specific for Group 1: 1. PNH Patients who have no history of treatment with any complement inhibitor at any dose. 2. PNH Type III erythrocyte or granulocyte clone size ≥10% 3. Absolute reticulocyte count ≥100×10\^9/liter \[L\]. 4. Anemia (Hgb \<10.5 grams/deciliter \[g/dL\]). 5. LDH ≥1.5× upper limit of normal. 6. Platelet count ≥30,000/microliter (µL) 7. Absolute neutrophil count (ANC) ≥750/ µL. Eligibility Criteria Specific for Group 2: 1. Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks 2. Anemia (Hgb \<10 g/dL) 3. Absolute reticulocyte count ≥100×10\^9/L 4. Platelet count ≥30,000/µL 5. Absolute neurophil count (ANC) ≥750/ µL Eligibility Criteria Specific for Group 3: 1\. Patient received danicopan during Study ACH471-103 Key
Exclusion criteria
1. History of a major organ transplant or hematopoietic stem cell/marrow transplant . 2. Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents for less than 24 weeks. 3. Known underlying bleeding disorders or any other conditions leading to anemia not primarily associated with PNH. 4. Estimated glomerular filtration rate \<30 milliliters/minute/1.73 meters squared and/or are on dialysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hgb at Week 12 | Baseline, Week 12 | Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. To address the impact of transfusion, Hgb values collected within 4 weeks after transfusion were not included in the primary efficacy analysis. Change from Baseline = Hgb at Week 12 - Baseline Hgb. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment | Baseline up to Week 12 | — |
| Number of Transfusion Instances During 12 Weeks of Treatment | Baseline up to Week 12 | — |
| Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12 | Baseline, Week 12 | Change from Baseline = Serum LDH levels at Week 12 - Baseline Serum LDH levels. |
| Change From Baseline in Absolute Reticulocyte Count at Week 12 | Baseline, Week 12 | Change from Baseline = absolute reticulocyte count at Week 12 - Baseline reticulocyte count. |
| Change From Baseline in Direct and Total Bilirubin at Week 12 | Baseline, Week 12 | — |
| Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12 | Baseline, Week 12 | The PNH RBC clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 12 - Baseline PNH clone size. |
| Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050 | Baseline up to Week 12 | Transfusion avoidance: participants remained transfusion-free and did not require a transfusion during the period of interest. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | From first dose of study drug up to Week 217 | An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as an AE that emerged during treatment, had been absent prior to treatment, or worsened relative to the pretreatment state. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period | Baseline, EOT visit (Maximum exposure: 213.4 weeks) | Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. Change from Baseline = Hgb at the EOT visit - Baseline Hgb. |
| Change From Baseline in LDH at the EOT During the LTE Period | Baseline, EOT visit (Maximum exposure: 213.4 weeks) | Change from Baseline = Serum LDH levels at the EOT visit - Baseline Serum LDH levels. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12 | Baseline, Week 12 | The FACIT-Fatigue scale is a collection of quality-of-life questionnaires pertaining to the management of fatigue symptoms due to 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. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores ranged from 0 to 52, with higher score indicating better quality of life. |
| Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period | Baseline, EOT visit (Maximum exposure: 213.4 weeks) | The FACIT-Fatigue scale is a collection of quality-of-life questionnaires pertaining to the management of fatigue symptoms due to 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. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores ranged from 0 to 52, with higher score indicating better quality of life. |
| Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12 | Baseline, Week 12 | C3 fragment deposition on PNH RBC was used as a marker of intra and extravascular hemolysis. Data are presented for the change from baseline to Week 12 in percentage of PNH RBCs with C3 fragment deposition. |
Countries
Canada, Italy, New Zealand, South Korea, Spain, Turkey (Türkiye), United Kingdom
Participant flow
Pre-assignment details
The study included a 12-week Treatment Period and a 148-week or 200-week (for sites in New Zealand) Long-term Extension (LTE) Period.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Treatment Naive Participants who were treatment-naive received ALXN2050 orally for 12 weeks during the treatment period. At the end of Week 12, participants entered the 148-week LTE Period and continued to receive ALXN2050 orally. | 12 |
| Group 2: Eculizumab Switch Participants who had received C5 inhibition with eculizumab for at least 6 months, who continued to experience anemia (Hgb \<10 grams/dL) and reticulocytes above the ULN, switched to ALXN2050 in this study and received ALXN2050 orally for 12 weeks during the treatment period. At the end of Week 12, participants entered the 148-week LTE Period and continued to receive ALXN2050 orally. | 11 |
| Group 3: Danicopan Rollover Participants who had received danicopan monotherapy during Study ACH471-103 (NCT03181633), switched to ALXN2050 in this study and received ALXN2050 orally for 12 weeks during the treatment period. At the end of Week 12, participants entered the 148-week LTE Period and continued to receive ALXN2050 orally. | 6 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| LTE Period | Study Termination | 11 | 11 | 5 |
| LTE Period | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1: Treatment Naive | Group 2: Eculizumab Switch | Group 3: Danicopan Rollover | Total |
|---|---|---|---|---|
| Age, Continuous | 43.75 years STANDARD_DEVIATION 17.099 | 42.45 years STANDARD_DEVIATION 13.419 | 40.50 years STANDARD_DEVIATION 16.718 | 42.59 years STANDARD_DEVIATION 15.186 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 10 Participants | 6 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| HgB | 81.17 grams/liter STANDARD_DEVIATION 11.731 | 91.00 grams/liter STANDARD_DEVIATION 9.602 | 130.67 grams/liter STANDARD_DEVIATION 19.18 | 95.14 grams/liter STANDARD_DEVIATION 22.662 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 10 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 6 |
| other Total, other adverse events | 12 / 12 | 10 / 11 | 6 / 6 |
| serious Total, serious adverse events | 7 / 12 | 5 / 11 | 2 / 6 |
Outcome results
Primary
Change From Baseline in Hgb at Week 12
Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. To address the impact of transfusion, Hgb values collected within 4 weeks after transfusion were not included in the primary efficacy analysis. Change from Baseline = Hgb at Week 12 - Baseline Hgb.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Hgb at Week 12 | 35.6 grams/liter | Standard Deviation 14.7 |
| Group 2: Eculizumab Switch | Change From Baseline in Hgb at Week 12 | 32.5 grams/liter | Standard Deviation 20.03 |
| Group 3: Danicopan Rollover | Change From Baseline in Hgb at Week 12 | -3.7 grams/liter | Standard Deviation 15.77 |
Secondary
Change From Baseline in Absolute Reticulocyte Count at Week 12
Change from Baseline = absolute reticulocyte count at Week 12 - Baseline reticulocyte count.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Absolute Reticulocyte Count at Week 12 | -100.6 10^3 cells/microliter (μL) | Standard Deviation 72.18 |
| Group 2: Eculizumab Switch | Change From Baseline in Absolute Reticulocyte Count at Week 12 | -179.0 10^3 cells/microliter (μL) | Standard Deviation 117.3 |
| Group 3: Danicopan Rollover | Change From Baseline in Absolute Reticulocyte Count at Week 12 | -24.0 10^3 cells/microliter (μL) | Standard Deviation 22.1 |
Secondary
Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12
C3 fragment deposition on PNH RBC was used as a marker of intra and extravascular hemolysis. Data are presented for the change from baseline to Week 12 in percentage of PNH RBCs with C3 fragment deposition.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12 | 0.0 percentage of PNH RBC | Standard Deviation 0 |
| Group 2: Eculizumab Switch | Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12 | -388.6 percentage of PNH RBC | Standard Deviation 590.08 |
| Group 3: Danicopan Rollover | Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12 | 0.3 percentage of PNH RBC | Standard Deviation 0.35 |
Secondary
Change From Baseline in Direct and Total Bilirubin at Week 12
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Direct and Total Bilirubin at Week 12 | Direct Bilirubin | -2.1 micromoles (μmol)/liter | Standard Deviation 2.1 |
| Group 1: Treatment Naive | Change From Baseline in Direct and Total Bilirubin at Week 12 | Total Bilirubin | -12.9 micromoles (μmol)/liter | Standard Deviation 10.07 |
| Group 2: Eculizumab Switch | Change From Baseline in Direct and Total Bilirubin at Week 12 | Direct Bilirubin | -6.3 micromoles (μmol)/liter | Standard Deviation 5.16 |
| Group 2: Eculizumab Switch | Change From Baseline in Direct and Total Bilirubin at Week 12 | Total Bilirubin | -23.3 micromoles (μmol)/liter | Standard Deviation 24.89 |
| Group 3: Danicopan Rollover | Change From Baseline in Direct and Total Bilirubin at Week 12 | Total Bilirubin | 1.5 micromoles (μmol)/liter | Standard Deviation 2.81 |
| Group 3: Danicopan Rollover | Change From Baseline in Direct and Total Bilirubin at Week 12 | Direct Bilirubin | 0.4 micromoles (μmol)/liter | Standard Deviation 0.89 |
Secondary
Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period
The FACIT-Fatigue scale is a collection of quality-of-life questionnaires pertaining to the management of fatigue symptoms due to 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. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores ranged from 0 to 52, with higher score indicating better quality of life.
Time frame: Baseline, EOT visit (Maximum exposure: 213.4 weeks)
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period | 12.6 units on a scale | Standard Deviation 12.51 |
| Group 2: Eculizumab Switch | Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period | 4.4 units on a scale | Standard Deviation 7.26 |
| Group 3: Danicopan Rollover | Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period | -3.4 units on a scale | Standard Deviation 10.26 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12
The FACIT-Fatigue scale is a collection of quality-of-life questionnaires pertaining to the management of fatigue symptoms due to 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. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores ranged from 0 to 52, with higher score indicating better quality of life.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12 | 11.2 units on a scale | Standard Deviation 13.2 |
| Group 2: Eculizumab Switch | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12 | 5.1 units on a scale | Standard Deviation 8.47 |
| Group 3: Danicopan Rollover | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12 | 0.2 units on a scale | Standard Deviation 3.13 |
Secondary
Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period
Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. Change from Baseline = Hgb at the EOT visit - Baseline Hgb.
Time frame: Baseline, EOT visit (Maximum exposure: 213.4 weeks)
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period | 44.9 grams/liter | Standard Deviation 21.07 |
| Group 2: Eculizumab Switch | Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period | 32.5 grams/liter | Standard Deviation 7.17 |
| Group 3: Danicopan Rollover | Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period | 2.4 grams/liter | Standard Deviation 19.44 |
Secondary
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12
Change from Baseline = Serum LDH levels at Week 12 - Baseline Serum LDH levels.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12 | -1310.8 units/liter | Standard Deviation 424.89 |
| Group 2: Eculizumab Switch | Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12 | 160.2 units/liter | Standard Deviation 279.57 |
| Group 3: Danicopan Rollover | Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12 | 88.7 units/liter | Standard Deviation 265 |
Secondary
Change From Baseline in LDH at the EOT During the LTE Period
Change from Baseline = Serum LDH levels at the EOT visit - Baseline Serum LDH levels.
Time frame: Baseline, EOT visit (Maximum exposure: 213.4 weeks)
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in LDH at the EOT During the LTE Period | -1084.1 units/liter | Standard Deviation 738.26 |
| Group 2: Eculizumab Switch | Change From Baseline in LDH at the EOT During the LTE Period | 95.7 units/liter | Standard Deviation 223.88 |
| Group 3: Danicopan Rollover | Change From Baseline in LDH at the EOT During the LTE Period | -61.4 units/liter | Standard Deviation 62.85 |
Secondary
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12
The PNH RBC clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 12 - Baseline PNH clone size.
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12 | 41.9 percentage of the total cell population | Standard Deviation 13.68 |
| Group 2: Eculizumab Switch | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12 | 27.5 percentage of the total cell population | Standard Deviation 21.6 |
| Group 3: Danicopan Rollover | Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12 | -12.0 percentage of the total cell population | Standard Deviation 26.94 |
Secondary
Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050
Transfusion avoidance: participants remained transfusion-free and did not require a transfusion during the period of interest.
Time frame: Baseline up to Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Treatment Naive | Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050 | 9 Participants |
| Group 2: Eculizumab Switch | Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050 | 10 Participants |
| Group 3: Danicopan Rollover | Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050 | 5 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as an AE that emerged during treatment, had been absent prior to treatment, or worsened relative to the pretreatment state. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: From first dose of study drug up to Week 217
Population: Safety set included all participants who received at least 1 dose of ALXN2050 in this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Treatment Naive | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | SAEs | 7 Participants |
| Group 1: Treatment Naive | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | Any AEs | 12 Participants |
| Group 1: Treatment Naive | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | AEs Leading to Discontinuation of Study Medication | 1 Participants |
| Group 2: Eculizumab Switch | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | SAEs | 5 Participants |
| Group 2: Eculizumab Switch | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | Any AEs | 10 Participants |
| Group 2: Eculizumab Switch | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | AEs Leading to Discontinuation of Study Medication | 1 Participants |
| Group 3: Danicopan Rollover | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | Any AEs | 6 Participants |
| Group 3: Danicopan Rollover | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | AEs Leading to Discontinuation of Study Medication | 0 Participants |
| Group 3: Danicopan Rollover | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication | SAEs | 2 Participants |
Secondary
Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment
Time frame: Baseline up to Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment | 0.6 RBC units | Standard Deviation 1.24 |
| Group 2: Eculizumab Switch | Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment | 0.1 RBC units | Standard Deviation 0.3 |
| Group 3: Danicopan Rollover | Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment | 0.8 RBC units | Standard Deviation 2.04 |
Secondary
Number of Transfusion Instances During 12 Weeks of Treatment
Time frame: Baseline up to Week 12
Population: Full analysis set included all participants who received at least 1 dose of ALXN2050 in this study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Treatment Naive | Number of Transfusion Instances During 12 Weeks of Treatment | 0.4 transfusion instances | Standard Deviation 0.9 |
| Group 2: Eculizumab Switch | Number of Transfusion Instances During 12 Weeks of Treatment | 0.1 transfusion instances | Standard Deviation 0.3 |
| Group 3: Danicopan Rollover | Number of Transfusion Instances During 12 Weeks of Treatment | 0.5 transfusion instances | Standard Deviation 1.22 |