Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy The secondary objectives of the study are: * To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of CH50 * To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran * To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements * To evaluate the effect of the combination treatment on hemoglobin levels * To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL) * To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma * To assess the immunogenicity of pozelimab and cemdisiran * To assess safety after dose intensification * To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)
Interventions
DRUGPozelimab
Intravenous (IV) loading dose (once) followed after 30 minutes by sub-cutaneous (SC) administration
DRUGCemdisiran
SC administration
Sponsors
Regeneron Pharmaceuticals
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
Key Inclusion Criteria: 1. Diagnosis of paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing 2. Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit Key
Exclusion criteria
1. History of bone marrow transplantation or receipt of an organ transplant 2. Body weight \<40 kg at screening 3. Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol 4. Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study 5. Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25% 6. No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment 7. Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care 8. Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period 9. Documented positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol 10. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases 11. Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol 12. Anticipated need for major surgery during the study NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 225 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period | Screening (Day 1) through Day 225 | — |
| OLTP: Percent Change in LDH From Pre-treatment Through Day 29 | Screening (Day 1) through Day 29 | — |
| OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32 | Baseline through Week 32 | — |
| OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32 | Week 4 through Week 32 | — |
| OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32 | Baseline through Week 32 | The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant. |
| OLTP: Rate of RBC Transfusions From Week 4 Through Week 32 | Week 4 through Week 32 | The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant. |
| OLTP: Number of RBC Units Transfused From Baseline Through Week 32 | Baseline through Week 32 | — |
| OLTP: Number of RBC Units Transfused From Week 4 Through Week 32 | Week 4 through Week 32 | — |
| OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32 | Baseline through Week 32 | Breakthrough hemolysis was defined as having an LDH ≥ 2 x upper limit of normal (ULN) and having signs or symptoms. |
| OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32 | Week 4 through Week 32 | Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms. |
| OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32 | Day 1 through Week 32 | Adequate control was defined as LDH ≤ 1.5 x ULN from Day 1 through Week 32. |
| OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32 | Week 8 through Week 32 | Adequate control was defined as LDH ≤ 1.5 x ULN from Week 8 through Week 32. |
| OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225 | Adequate control at a visit was defined as having LDH ≤1.5 x ULN at that visit. |
| OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225 | Normalization was defined as LDH ≤ 1.0 x ULN at that visit. |
| OLTP: Average LDH From Baseline Through Week 32 | Baseline through Week 32 | The trapezoidal rule was used to calculate area under the curve (AUC). Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period. |
| OLTP: Average LDH From Week 8 Through Week 32 | Week 8 through Week 32 | The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period. |
| OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32 | Baseline through Week 32 | Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 grams per deciliter (g/dL). |
| OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32 | Week 4 through Week 32 | Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL. |
| OLTP: Change From Baseline in Hemoglobin Levels | Baseline, Week 32 | — |
| OLTP: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score | Baseline, Week 32 | The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in participants with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life. |
| OLTP: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by the Global Health Status Subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale | Baseline, Week 32 | EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. The GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life. |
| OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30 | Baseline, Week 32 | EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life. |
| OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) | Baseline through Week 32 | This assay assessed the activity of the classical pathway of complement to measure C5 activity. |
| OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Days 28, 56, 84, 112, 140, 168, 196, 224, 392, 588; Post-dose Day 28 | — |
| OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Days 0, 14, 28, 56, 84, 112, 140, 168, 196, 224 | — |
| OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose and Post-dose Days 0, 84, 196, 224, 588 | — |
| OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Days 0, 7, 14, 28, 56, 84, 112, 140, 168, 196, 224, 392, 588 | — |
| OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA) | Baseline through Week 32 | — |
| OLTP: Number of Participants With Cemdisiran ADA | Baseline through Week 32 | — |
| OLTP: Number of Participants Who Received Dose Intensification With TEAEs | Baseline through Week 32 | — |
| OLEP: Number of Participants With TEAEs | Day 1 through Week 52 of the OLEP | — |
| OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | — |
| OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | — |
| OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | — |
| OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | — |
| OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant. |
| OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant. |
| OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | — |
| OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms. |
| OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms. |
| OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | Adequate control was defined as LDH ≤ 1.5 x ULN. |
| OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | Adequate control was defined as LDH ≤ 1.5 x ULN. |
| OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP | Adequate control was defined as LDH ≤ 1.5 x ULN at that visit. |
| OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP | Normalization was defined as LDH ≤ 1.0 x ULN at that visit. |
| OLEP: Average LDH From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period. |
| OLEP: Average LDH From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period. |
| OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP | Day 1 through Week 24 of the OLEP | Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL. |
| OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL. |
| OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP | Day 1 through Week 52 of the OLEP | — |
| OLEP: Change From Baseline in FACIT-Fatigue Score | Day 1 and Week 52 of the OLEP | The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life. |
| OLEP: Change From Baseline in HRQoL as Measured by the Global Health Status Subscale of the EORTC-QLQ-30 Scale | Day 1 and Week 52 of the OLEP | EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life. |
| OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30 | Day 1 and Week 52 of the OLEP | EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life. |
| OLEP: Change From Baseline in CH50 | Baseline, Week 16, Week 32, Week 52 of the OLEP | This assay assessed the activity of the classical pathway of complement to measure C5 activity. |
| OLEP: Number of Participants With Pozelimab ADA | Day 1 through Week 52 of the OLEP | — |
| OLEP: Number of Participants With Cemdisiran ADA | Day 1 through Week 52 of the OLEP | — |
| OLEP: Change From Baseline in Hemoglobin Levels | Day 1 and Week 24 of the OLEP | — |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total of 7 participants were screened and 6 were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Participants With PNH Participants received cemdisiran by subcutaneous (SC) injection along with their usual dose of eculizumab by intravenous (IV) infusion. After completion of Open Label Treatment Period (OLTP), for participants who willing to continue to receive study treatment, SC pozelimab and cemdisiran Q4W were administered up to 52 weeks during the Open-Label Extension Period (OLEP) | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Open-Label Treatment (OLTP) (32 Weeks) | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Participants With PNH |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 1 / 6 | 1 / 5 |
Outcome results
Primary
OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to Day 225
Population: The safety analysis set included all participants who received any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Secondary
OLEP: Average LDH From Day 1 Through Week 24 of the OLEP
The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Average LDH From Day 1 Through Week 24 of the OLEP | 210.55 U/L | Standard Deviation 42.64 |
Secondary
OLEP: Average LDH From Day 1 Through Week 52 of the OLEP
The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Average LDH From Day 1 Through Week 52 of the OLEP | 210.13 U/L | Standard Deviation 44.91 |
Secondary
OLEP: Change From Baseline in CH50
This assay assessed the activity of the classical pathway of complement to measure C5 activity.
Time frame: Baseline, Week 16, Week 32, Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in CH50 | Change at Week 16 | 0.0 IU/mL | Standard Deviation 0 |
| Participants With PNH | OLEP: Change From Baseline in CH50 | Change at Week 32 | 0.6 IU/mL | Standard Deviation 1.3 |
| Participants With PNH | OLEP: Change From Baseline in CH50 | Change at Week 52 | 1.2 IU/mL | Standard Deviation 1.8 |
Secondary
OLEP: Change From Baseline in FACIT-Fatigue Score
The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life.
Time frame: Day 1 and Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in FACIT-Fatigue Score | -2.4 score on a scale | Standard Deviation 8.7 |
Secondary
OLEP: Change From Baseline in Hemoglobin Levels
Time frame: Day 1 and Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in Hemoglobin Levels | -0.10 g/dL | Standard Deviation 0.52 |
Secondary
OLEP: Change From Baseline in Hemoglobin Levels
Time frame: Day 1 and Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in Hemoglobin Levels | 0.16 g/dL | Standard Deviation 0.7 |
Secondary
OLEP: Change From Baseline in HRQoL as Measured by the Global Health Status Subscale of the EORTC-QLQ-30 Scale
EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.
Time frame: Day 1 and Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in HRQoL as Measured by the Global Health Status Subscale of the EORTC-QLQ-30 Scale | -10.000 score on a scale | Standard Deviation 18.066 |
Secondary
OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30
EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.
Time frame: Day 1 and Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30 | 0.000 score on a scale | Standard Deviation 4.714 |
Secondary
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Adequate control was defined as LDH ≤ 1.5 x ULN at that visit.
Time frame: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Baseline OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 57 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 113 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 169 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 225 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 281 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP | Day 365 OLEP | 5 Participants |
Secondary
OLEP: Number of Participants With Cemdisiran ADA
Time frame: Day 1 through Week 52 of the OLEP
Population: The ADA-OLEP analysis set included all participants who received study drug in the OLEP and had at least 1 non-missing ADA result following the first OLEP dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLEP: Number of Participants With Cemdisiran ADA | 0 Participants |
Secondary
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Normalization was defined as LDH ≤ 1.0 x ULN at that visit.
Time frame: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 365 OLEP | 4 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Baseline OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 57 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 113 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 169 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 225 OLEP | 5 Participants |
| Participants With PNH | OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP | Day 281 OLEP | 5 Participants |
Secondary
OLEP: Number of Participants With Pozelimab ADA
Time frame: Day 1 through Week 52 of the OLEP
Population: The ADA-OLEP analysis set included all participants who received study drug in the OLEP and had at least 1 non-missing ADA result following the first OLEP dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLEP: Number of Participants With Pozelimab ADA | 0 Participants |
Secondary
OLEP: Number of Participants With TEAEs
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP safety analysis set included all participants who participated in the OLEP who received any amount of study drug in the OLEP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLEP: Number of Participants With TEAEs | 5 Participants |
Secondary
OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP | 0 RBC units | Standard Deviation 0 |
Secondary
OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP | 0.4 RBC units | Standard Deviation 0.9 |
Secondary
OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP
Adequate control was defined as LDH ≤ 1.5 x ULN.
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP | 100 percentage of participants |
Secondary
OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP
Adequate control was defined as LDH ≤ 1.5 x ULN.
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP | 100 percentage of participants |
Secondary
OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP | 100 percentage of participants |
Secondary
OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP | 80.0 percentage of participants |
Secondary
OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP | 0.0 percentage of participants |
Secondary
OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP | 0.0 percentage of participants |
Secondary
OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP | 100 percentage of participants |
Secondary
OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP | 80.0 percentage of participants |
Secondary
OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP | -6.17 percent change | Standard Deviation 9.15 |
Secondary
OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP | -3.46 percent change | Standard Deviation 10.94 |
Secondary
OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP
The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.
Time frame: Day 1 through Week 24 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP | 0 transfusions per person-year |
Secondary
OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP
The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.
Time frame: Day 1 through Week 52 of the OLEP
Population: The OLEP FAS included all participants who participated in the OLEP who received any amount of study drug in the OLEP and had at least 1 post-baseline assessment in the OLEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP | 0.200 transfusions per person-year |
Secondary
OLTP and OLEP: Concentration of Total C5 in Plasma
Time frame: Pre-dose Days 0, 7, 14, 28, 56, 84, 112, 140, 168, 196, 224, 392, 588
Population: The PK analysis population included all participants who received any amount of study drug and who had at least 1 non-missing result following the first dose of study drug. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 0 | 320 mg/L | Standard Deviation 64.2 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-Dose Day 7 | 191 mg/L | Standard Deviation 46.2 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 14 | 118 mg/L | Standard Deviation 28 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 28 | 54.5 mg/L | Standard Deviation 14.2 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 56 | 2.77 mg/L | Standard Deviation 6.78 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 84 | 2.90 mg/L | Standard Deviation 6.48 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 112 | 3.88 mg/L | Standard Deviation 7.75 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 140 | 3.10 mg/L | Standard Deviation 6.93 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 168 | 4.79 mg/L | Standard Deviation 7.18 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 196 | 2.03 mg/L | Standard Deviation 4.05 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 224 | 4.96 mg/L | Standard Deviation 7.44 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 392 | 5.02 mg/L | Standard Deviation 7.13 |
| Participants With PNH | OLTP and OLEP: Concentration of Total C5 in Plasma | Pre-dose Day 588 | 5.28 mg/L | Standard Deviation 7.44 |
Secondary
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Time frame: Pre-dose and Post-dose Days 0, 84, 196, 224, 588
Population: The PK analysis population included all participants who received any amount of study drug and who had at least 1 non-missing result following the first dose of study drug. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose Day 0 | 0 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Post-dose Day 0 | 139 nanograms per milliliter (ng/mL) | Standard Deviation 45.5 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose Day 84 | 0 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Post-dose Day 84 | 178 nanograms per milliliter (ng/mL) | Standard Deviation 111 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose Day 196 | 0 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Post-dose Day 196 | 196 nanograms per milliliter (ng/mL) | Standard Deviation 100 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose Day 224 | 0 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Post-dose Day 224 | 158 nanograms per milliliter (ng/mL) | Standard Deviation 75.7 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Pre-dose Day 588 | 0 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Cemdisiran in Plasma | Post-dose Day 588 | 215 nanograms per milliliter (ng/mL) | Standard Deviation 84.8 |
Secondary
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Time frame: Pre-dose Days 28, 56, 84, 112, 140, 168, 196, 224, 392, 588; Post-dose Day 28
Population: The pharmacokinetic (PK) analysis population included all participants who received any amount of study drug and who had at least 1 non-missing result following the first dose of study drug. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 28 | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | 15 Minutes Post-dose Day 28 | 1280 milligrams per liter (mg/L) | Standard Deviation 193 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 56 | 333 milligrams per liter (mg/L) | Standard Deviation 48.1 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 84 | 189 milligrams per liter (mg/L) | Standard Deviation 54.8 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 112 | 121 milligrams per liter (mg/L) | Standard Deviation 57.2 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 140 | 102 milligrams per liter (mg/L) | Standard Deviation 40.7 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 168 | 70.1 milligrams per liter (mg/L) | Standard Deviation 37.3 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 196 | 86.1 milligrams per liter (mg/L) | Standard Deviation 36.6 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 224 | 71.7 milligrams per liter (mg/L) | Standard Deviation 41.4 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 392 | 53.1 milligrams per liter (mg/L) | Standard Deviation 25.6 |
| Participants With PNH | OLTP and OLEP: Concentration of Total Pozelimab in Serum | Pre-dose Day 588 | 51.1 milligrams per liter (mg/L) | Standard Deviation 25.6 |
Secondary
OLTP: Average LDH From Baseline Through Week 32
The trapezoidal rule was used to calculate area under the curve (AUC). Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Average LDH From Baseline Through Week 32 | 227.34 Units per Liter (U/L) | Standard Deviation 45.08 |
Secondary
OLTP: Average LDH From Week 8 Through Week 32
The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.
Time frame: Week 8 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Average LDH From Week 8 Through Week 32 | 223.49 U/L | Standard Deviation 49.01 |
Secondary
OLTP: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score
The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in participants with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life.
Time frame: Baseline, Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Participants With PNH | OLTP: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score | -1.0 score on a scale |
Secondary
OLTP: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by the Global Health Status Subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale
EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. The GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.
Time frame: Baseline, Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Participants With PNH | OLTP: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by the Global Health Status Subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale | -8.333 score on a scale |
Secondary
OLTP: Change From Baseline in Hemoglobin Levels
Time frame: Baseline, Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Change From Baseline in Hemoglobin Levels | 0.54 g/dL | Standard Deviation 0.6 |
Secondary
OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30
EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.
Time frame: Baseline, Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Participants With PNH | OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30 | 6.667 score on a scale |
Secondary
OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50)
This assay assessed the activity of the classical pathway of complement to measure C5 activity.
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) | 0.0 International units per mL (IU/mL) | Standard Deviation 0 |
Secondary
OLTP: Concentration of Total Eculizumab in Serum
Time frame: Pre-dose Days 0, 14, 28, 56, 84, 112, 140, 168, 196, 224
Population: The PK analysis population included all participants who received any amount of study drug and who had at least 1 non-missing result following the first dose of study drug. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 224 | 0.540 mg/L | Standard Deviation 1.16 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 0 | 231 mg/L | Standard Deviation 64.5 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 14 | 225 mg/L | Standard Deviation 63.2 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 28 | 242 mg/L | Standard Deviation 59 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 56 | 101 mg/L | Standard Deviation 42.9 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 84 | 44.4 mg/L | Standard Deviation 38.7 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 112 | 22.5 mg/L | Standard Deviation 29.5 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 140 | 12.6 mg/L | Standard Deviation 12.5 |
| Participants With PNH | OLTP: Concentration of Total Eculizumab in Serum | Pre-dose Day 168 | 4.23 mg/L | Standard Deviation 6.46 |
Secondary
OLTP: Number of Participants Who Received Dose Intensification With TEAEs
Time frame: Baseline through Week 32
Population: No participants required treatment intensification during the study.
Secondary
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Adequate control at a visit was defined as having LDH ≤1.5 x ULN at that visit.
Time frame: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 1 | 6 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 8 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 15 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 29 | 6 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 43 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 57 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 71 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 85 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 113 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 141 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 169 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 197 | 3 Participants |
| Participants With PNH | OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit | Day 225 | 5 Participants |
Secondary
OLTP: Number of Participants With Cemdisiran ADA
Time frame: Baseline through Week 32
Population: The ADA analysis set included all participants who received study drug and had at least 1 non-missing ADA result following the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLTP: Number of Participants With Cemdisiran ADA | 0 Participants |
Secondary
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Normalization was defined as LDH ≤ 1.0 x ULN at that visit.
Time frame: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 85 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 113 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 141 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 225 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 1 | 6 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 8 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 15 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 29 | 6 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 43 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 57 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 71 | 5 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 169 | 4 Participants |
| Participants With PNH | OLTP: Number of Participants With Normalization of Their LDH at Each Visit | Day 197 | 3 Participants |
Secondary
OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA)
Time frame: Baseline through Week 32
Population: The ADA analysis set included all participants who received study drug and had at least 1 non-missing ADA result following the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With PNH | OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA) | 0 Participants |
Secondary
OLTP: Number of RBC Units Transfused From Baseline Through Week 32
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Number of RBC Units Transfused From Baseline Through Week 32 | 0 RBC units | Standard Deviation 0 |
Secondary
OLTP: Number of RBC Units Transfused From Week 4 Through Week 32
Time frame: Week 4 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Number of RBC Units Transfused From Week 4 Through Week 32 | 0 RBC units | Standard Deviation 0 |
Secondary
OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32
Adequate control was defined as LDH ≤ 1.5 x ULN from Day 1 through Week 32.
Time frame: Day 1 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32 | 83.3 percentage of participants |
Secondary
OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32
Adequate control was defined as LDH ≤ 1.5 x ULN from Week 8 through Week 32.
Time frame: Week 8 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32 | 83.3 percentage of participants |
Secondary
OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32 | 100 percentage of participants |
Secondary
OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32
Time frame: Week 4 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32 | 100 percentage of participants |
Secondary
OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32
Breakthrough hemolysis was defined as having an LDH ≥ 2 x upper limit of normal (ULN) and having signs or symptoms.
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32 | 0.0 percentage of participants |
Secondary
OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Time frame: Week 4 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32 | 0.0 percentage of participants |
Secondary
OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 grams per deciliter (g/dL).
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32 | 100 percentage of participants |
Secondary
OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Time frame: Week 4 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32 | 100 percentage of participants |
Secondary
OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
Time frame: Screening (Day 1) through Day 225
Population: The full analysis set (FAS) included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period | -0.95 percent change | Standard Deviation 13.4 |
Secondary
OLTP: Percent Change in LDH From Pre-treatment Through Day 29
Time frame: Screening (Day 1) through Day 29
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With PNH | OLTP: Percent Change in LDH From Pre-treatment Through Day 29 | 3.61 percent change | Standard Deviation 35.99 |
Secondary
OLTP: Rate of RBC Transfusions From Week 4 Through Week 32
The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Time frame: Week 4 through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Rate of RBC Transfusions From Week 4 Through Week 32 | 0 transfusions per person-year |
Secondary
OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32
The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Time frame: Baseline through Week 32
Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With PNH | OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32 | 0 transfusions per person-year |