Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP) 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 total complement hemolysis activity (CH50) * To evaluate the effect of the combination treatment on hemoglobin levels * To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements * To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life * To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma * To assess immunogenicity to pozelimab and cemdisiran * To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP) * To assess safety after treatment intensification with pozelimab and cemdisiran
Interventions
DRUGPozelimab
Administered Sub-cutaneous (SC) per protocol
DRUGCemdisiran
Administered SC per protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1\. Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470) Key
Exclusion criteria
1. Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol 2. Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol 3. Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol 4. Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant 5. Known hypersensitivity to cemdisiran or any component of cemdisiran formulation NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Through Week 28 | Open Label Treatment Period (OLTP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28 | Baseline (Day 1) through Week 28 | OLTP Adequate control of hemolysis is defined as LDH values ≤1.5 × Upper limit of normal (ULN) from baseline (day 1) to week 28 |
| Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28 | Week 4 through Week 28 | OLTP |
| Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Day 1 through Week 28 | OLTP; Adequate control at a visit is defined as having LDH \<=1.5 x ULN at that visit |
| Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Baseline (Day 1) through Week 28 | OLTP; Normalization of LDH was defined as LDH ≤1.0 × ULN at each visit |
| Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28 | Baseline (Day 1) through Week 28 | OLTP |
| Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28 | Week 4 through Week 28 | OLTP |
| Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28 | Baseline (Day 1) through Week 28 | OLTP Breakthrough hemolysis is defined as an increase in LDH with concomitant signs or symptoms associated with hemolysis: • An increase in LDH occurs when: * LDH ≥2 × ULN if pre-treatment LDH is ≤1.5 × ULN or * LDH ≥2 × ULN after initial achievement of LDH ≤1.5 × ULN if pre-treatment LDH is \>1.5 × ULN Signs or symptoms should correspond to those known to be associated with intravascular hemolysis due to Paroxysmal nocturnal hemoglobinuria (PNH) limited to the following: new onset or worsening fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, scleral icterus, erectile dysfunction, chest pain, confusion, dysphagia, anemia including hemoglobin value significantly lower (ie, ≥2g/dL decrease) compared to patient's known baseline hemoglobin values, and thrombotic event. |
| Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28 | Baseline (Day 1) through Week 28 | OLTP Hemoglobin stabilization was defined as participants who did not receive an RBC transfusion and had no decrease in hemoglobin level of ≥2 grams per deciLiter (g/dL). |
| Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP |
| Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP Not requiring a red blood cell (RBC) transfusion as per protocol algorithm |
| Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28 | Baseline (Day 1) to Week 28 | OLTP Rate of RBCs transfused is defined as number of events per person-years of treatment. For each participant, the participant-years are the time from first dose date to week 28 (or early terminations visit if subject discontinued the study early) in the OLTP. |
| Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP |
| Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP |
| Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP FACIT fatigue is a 13-item scale and for each item 4 is not at all fatigued to 0 very much fatigued. Higher FACIT-Fatigue scores indicate less fatigue (scores range from 0-52). A 5-point change is considered clinically meaningful. |
| Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement. |
| Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28 | Baseline (Day 1) to Week 28 | OLTP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement. |
| Concentrations of Total Pozelimab in Serum on Week 28 | On Week 28 | OLTP |
| Concentrations of Cemdisiran in Plasma on Week 28 | On Week 28 | OLTP |
| Concentrations of Total C5 on Week 28 | On Week 28 | OLTP |
| Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52]) | OLTP and OLEP |
| Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52]) | OLTP and OLEP |
| Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification | Through Week 28 | OLTP No participants received dose intensification during the study; Therefore, assessment of the safety of pozelimab + cemdisiran combination therapy in participants requiring dose intensification was not conducted. |
| Change of LDH From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | Optional Open-Label Extension Period (OLEP) |
| Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP; Percentage of change for units per liter (U/L) |
| Change of LDH From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Percent Change of LDH From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e | Baseline (Day 1e) through Week 24e | OLEP |
| Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through Week 52e | OLEP |
| Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through Week 52e | OLEP Adequate control at a visit is defined as having LDH \<=1.5 x ULN at that visit |
| Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through week 52e | OLEP |
| Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through Week 52e | OLEP |
| Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e | Baseline (Day 1e) through Week 24e | OLEP |
| Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through Week 52e | OLEP |
| Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e | Baseline (Day 1e) through Week 24e | OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels |
| Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) through Week 52e | OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels |
| Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP |
| Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e | Baseline (Day 1e) through Week 24e | OLEP Not requiring a RBC transfusion as per protocol algorithm |
| Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e | Baseline (Day 1e) to Week 52e | OLEP Not requiring a RBC transfusion as per protocol algorithm |
| Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP |
| Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP |
| Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Change in CH50 From Baseline (Day 1e) to Week 16e | Baseline (Day 1e) to Week 16e | OLEP |
| Change in CH50 From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP |
| Change in CH50 From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Percent Change in CH50 From Baseline (Day 1e) to Week 16e | Baseline (Day 1e) to Week 16e | OLEP |
| Percent Change in CH50 From Baseline (Day 1e) to Week 24e | Baseline (Day 1e) to Week 24e | OLEP |
| Percent Change in CH50 From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP |
| Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period | End of treatment period, approximately 28 Weeks | OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28); percentage of change in Upper Limit of Normal (xULN). |
| Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement. |
| Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement. |
| Percentage of Participants With TEAEs Up to Week 52 | Up to Week 52 | OLEP |
| Concentrations of Total Pozelimab in Serum on Week 52 | On Week 52 | OLEP |
| Concentrations of Total C5 on Week 52 | On Week 52 | OLEP |
| Concentrations of Cemdisiran in Plasma on Week 52 | On Week 52 | OLEP |
| Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e | Baseline (Day 1e) to Week 52e | OLEP; The FACIT-Fatigue is a 13-item, self-administered assessment of 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 QoL in participants with cancer and other chronic illnesses. The FACIT-Fatigue items are measured with a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating less fatigue. A 5-point change is considered clinically meaningful. |
Countries
Hong Kong, Hungary, Malaysia, South Korea, Taiwan, United Kingdom
Participant flow
Pre-assignment details
Twenty-four participants were screened and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Pozelimab Q2W + Cemdisiran Pozelimab administered by subcutaneous (SC) injection every 2 weeks (Q2W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment (pozelimab Q2W + cemdisiran) was administered on day 1 of the open-label treatment period (OLTP). In the open- label extension period (OLEP), participants received a regimen of pozelimab + cemdisiran, regardless of their treatment assignment in the OLTP. | 12 |
| Pozelimab Q4W + Cemdisiran Pozelimab administered by subcutaneous (SC) injection every 4 weeks (Q4W) and cemdisiran administered by subcutanous (SC) injection. The first dose of the combination treatment was administered on day 1 of the OLTP. In the OLEP, participants received a regimen of pozelimab Q4W + cemdisiran, regardless of their treatment assignment in the OLTP. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Pozelimab Q2W + Cemdisiran | Pozelimab Q4W + Cemdisiran | Total |
|---|---|---|---|
| Age, Continuous | 41.4 Years STANDARD_DEVIATION 16.89 | 53.2 Years STANDARD_DEVIATION 16.38 | 47.3 Years STANDARD_DEVIATION 17.34 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 11 Participants | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 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 / 12 | 0 / 23 |
| other Total, other adverse events | 8 / 12 | 5 / 12 | 10 / 23 |
| serious Total, serious adverse events | 3 / 12 | 0 / 12 | 2 / 23 |
Outcome results
Primary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Open Label Treatment Period (OLTP)
Time frame: Through Week 28
Population: Safety analysis set (SAF) included all randomized participants who received any amount of study drug and was based on the treatment received (as treated); Here 'number analyzed' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with any TEAE | 66.7 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with serious TEAE | 16.7 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with severe TEAE | 16.7 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with any TEAE | 41.7 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with serious TEAE | 0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants with severe TEAE | 0 Percentage of participants |
Secondary
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e
OLEP
Time frame: Baseline (Day 1e) through Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e | 154.63 U/L | Standard Deviation 38.231 |
Secondary
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28
OLTP
Time frame: Baseline (Day 1) through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28 | 238.18 Units per Liter (U/L) | Standard Deviation 44.006 |
| Pozelimab Q4W + Cemdisiran | Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28 | 244.42 Units per Liter (U/L) | Standard Deviation 39.085 |
Secondary
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28
OLTP
Time frame: Week 4 through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28 | 202.49 U/L | Standard Deviation 38.272 |
| Pozelimab Q4W + Cemdisiran | Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28 | 211.28 U/L | Standard Deviation 34.28 |
Secondary
Change in CH50 From Baseline (Day 1e) to Week 16e
OLEP
Time frame: Baseline (Day 1e) to Week 16e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in CH50 From Baseline (Day 1e) to Week 16e | 0.0 U/mL | Standard Deviation 0 |
Secondary
Change in CH50 From Baseline (Day 1e) to Week 24e
OLEP
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint; No CH50 samples were collected at Week 24e
Secondary
Change in CH50 From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in CH50 From Baseline (Day 1e) to Week 52e | 0.0 U/mL | Standard Deviation 0.21 |
Secondary
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e
OLEP; The FACIT-Fatigue is a 13-item, self-administered assessment of 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 QoL in participants with cancer and other chronic illnesses. The FACIT-Fatigue items are measured with a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating less fatigue. A 5-point change is considered clinically meaningful.
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e | -0.9 Score on a scale | Standard Deviation 5.95 |
Secondary
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28
OLTP FACIT fatigue is a 13-item scale and for each item 4 is not at all fatigued to 0 very much fatigued. Higher FACIT-Fatigue scores indicate less fatigue (scores range from 0-52). A 5-point change is considered clinically meaningful.
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28 | -6.0 Score on a scale | Standard Deviation 10.09 |
| Pozelimab Q4W + Cemdisiran | Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28 | -2.0 Score on a scale | Standard Deviation 4.36 |
Secondary
Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e | 6.0 Score on a scale | Standard Deviation 13.73 |
Secondary
Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28
OLTP EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28 | -9.4 Score on a scale | Standard Deviation 23.33 |
| Pozelimab Q4W + Cemdisiran | Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28 | -1.9 Score on a scale | Standard Deviation 13.03 |
Secondary
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e
OLEP
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e | 0.8 g/L | Standard Deviation 15.63 |
Secondary
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e | -0.6 g/L | Standard Deviation 12.6 |
Secondary
Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28
OLTP
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28 | -1.3 grams per Liter (g/L) | Standard Deviation 13.77 |
| Pozelimab Q4W + Cemdisiran | Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28 | 10.3 grams per Liter (g/L) | Standard Deviation 7.41 |
Secondary
Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e | -0.3 Score on a scale | Standard Deviation 3.93 |
Secondary
Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28
OLTP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 (very poor) to 7 (excellent). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28 | -6.7 Score on a scale | Standard Deviation 19.19 |
| Pozelimab Q4W + Cemdisiran | Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28 | 0.7 Score on a scale | Standard Deviation 9.09 |
Secondary
Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28
OLTP
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28 | 0.0 Units per milliliter (U/mL) | Standard Deviation 0 |
| Pozelimab Q4W + Cemdisiran | Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28 | -0.1 Units per milliliter (U/mL) | Standard Deviation 0.29 |
Secondary
Change of LDH From Baseline (Day 1e) to Week 24e
Optional Open-Label Extension Period (OLEP)
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change of LDH From Baseline (Day 1e) to Week 24e | -18.2 U/L | Standard Deviation 108.4 |
Secondary
Change of LDH From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Change of LDH From Baseline (Day 1e) to Week 52e | -14.5 U/L | Standard Deviation 105.9 |
Secondary
Concentrations of Cemdisiran in Plasma on Week 28
OLTP
Time frame: On Week 28
Population: The pharmacokinetic (PK) analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Cemdisiran in Plasma on Week 28 | NA mg/L |
| Pozelimab Q4W + Cemdisiran | Concentrations of Cemdisiran in Plasma on Week 28 | NA mg/L |
Secondary
Concentrations of Cemdisiran in Plasma on Week 52
OLEP
Time frame: On Week 52
Population: The OLEP pharmacokinetic (PK) analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Cemdisiran in Plasma on Week 52 | NA mg/L |
| Pozelimab Q4W + Cemdisiran | Concentrations of Cemdisiran in Plasma on Week 52 | NA mg/L |
Secondary
Concentrations of Total C5 on Week 28
OLTP
Time frame: On Week 28
Population: The pharmacokinetic (PK) analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Total C5 on Week 28 | 0 mg/L |
| Pozelimab Q4W + Cemdisiran | Concentrations of Total C5 on Week 28 | 0 mg/L |
Secondary
Concentrations of Total C5 on Week 52
OLEP
Time frame: On Week 52
Population: The OLEP pharmacokinetic (PK) analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Total C5 on Week 52 | 0 mg/L |
| Pozelimab Q4W + Cemdisiran | Concentrations of Total C5 on Week 52 | NA mg/L |
Secondary
Concentrations of Total Pozelimab in Serum on Week 28
OLTP
Time frame: On Week 28
Population: The pharmacokinetic (PK) analysis set includes all treated participants who received any amount of study drug (SAF) and who had at least 1 non-missing analyte measurement following the first dose of combination treatment. The PK analysis set is based on the actual treatment received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Total Pozelimab in Serum on Week 28 | 131 mg/L | Standard Deviation 74.8 |
| Pozelimab Q4W + Cemdisiran | Concentrations of Total Pozelimab in Serum on Week 28 | 58.2 mg/L | Standard Deviation 31.5 |
Secondary
Concentrations of Total Pozelimab in Serum on Week 52
OLEP
Time frame: On Week 52
Population: The OLEP pharmacokinetic (PK) analysis set includes all participants who participated in the OLEP who received any amount of study drug in the OLEP and who had at least 1 non-missing analyte measurement following the first dose of study drug in the OLEP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Concentrations of Total Pozelimab in Serum on Week 52 | 63.4 mg/L | Standard Deviation 35.6 |
| Pozelimab Q4W + Cemdisiran | Concentrations of Total Pozelimab in Serum on Week 52 | 58.6 mg/L | Standard Deviation 28.7 |
Secondary
Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time
OLTP and OLEP
Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Population: Anti-Drug Antibodies (ADA) Analysis Set; Here 'n' = the number of evaluable participants at a certain timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Boosted Response | 0 Participants |
| Pozelimab Q2W + Cemdisiran | Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Emergent Response | 0 Participants |
| Pozelimab Q4W + Cemdisiran | Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Boosted Response | 0 Participants |
| Pozelimab Q4W + Cemdisiran | Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Emergent Response | 1 Participants |
Secondary
Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time
OLTP and OLEP
Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Population: Anti-Drug Antibodies (ADA) Analysis Set; Here 'n' = the number of evaluable participants at a certain timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Boosted Response | 0 Participants |
| Pozelimab Q2W + Cemdisiran | Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Emergent Response | 0 Participants |
| Pozelimab Q4W + Cemdisiran | Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Boosted Response | 0 Participants |
| Pozelimab Q4W + Cemdisiran | Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time | Treatment-Emergent Response | 0 Participants |
Secondary
Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28
OLTP
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28 | 1.5 Units | Standard Deviation 3.73 |
| Pozelimab Q4W + Cemdisiran | Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28 | 0.0 Units | Standard Deviation 0 |
Secondary
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e
OLEP
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e | 0.4 Units | Standard Deviation 1.47 |
Secondary
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e | 0.9 Units | Standard Deviation 3.95 |
Secondary
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e
OLEP
Time frame: Baseline (Day 1e) through Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e | 95.7 Percentage of Participants |
Secondary
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e
OLEP
Time frame: Baseline (Day 1e) through Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e | 95.7 Percentage of Participants |
Secondary
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28
OLTP Adequate control of hemolysis is defined as LDH values ≤1.5 × Upper limit of normal (ULN) from baseline (day 1) to week 28
Time frame: Baseline (Day 1) through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' is the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28 | 75.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28 | 91.7 Percentage of participants |
Secondary
Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28
OLTP
Time frame: Week 4 through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28 | 83.3 Percentage of Participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28 | 91.7 Percentage of Participants |
Secondary
Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28
OLTP; Adequate control at a visit is defined as having LDH \<=1.5 x ULN at that visit
Time frame: Day 1 through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 1 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 10 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 4 | 83.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 12 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Pre-treatment | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 16 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 6 | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 20 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 2 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 24 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 8 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 28 | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Baseline Visit (Day 1) | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 28 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Baseline Visit (Day 1) | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Pre-treatment | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 1 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 2 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 4 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 6 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 8 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 10 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 12 | 92.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 16 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 20 | 100.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 | Week 24 | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e
OLEP Adequate control at a visit is defined as having LDH \<=1.5 x ULN at that visit
Time frame: Baseline (Day 1e) through Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | OLEP Baseline (Day 1e) | 96.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 8e | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 16e | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 24e | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 32e | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 40e | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e | Week 52e | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e
OLEP
Time frame: Baseline (Day 1e) through Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e | 4.3 Percentage of Participants |
Secondary
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e
OLEP
Time frame: Baseline (Day 1e) through Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e | 4.3 Percentage of participants |
Secondary
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28
OLTP Breakthrough hemolysis is defined as an increase in LDH with concomitant signs or symptoms associated with hemolysis: • An increase in LDH occurs when: * LDH ≥2 × ULN if pre-treatment LDH is ≤1.5 × ULN or * LDH ≥2 × ULN after initial achievement of LDH ≤1.5 × ULN if pre-treatment LDH is \>1.5 × ULN Signs or symptoms should correspond to those known to be associated with intravascular hemolysis due to Paroxysmal nocturnal hemoglobinuria (PNH) limited to the following: new onset or worsening fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, scleral icterus, erectile dysfunction, chest pain, confusion, dysphagia, anemia including hemoglobin value significantly lower (ie, ≥2g/dL decrease) compared to patient's known baseline hemoglobin values, and thrombotic event.
Time frame: Baseline (Day 1) through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28 | 8.3 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28 | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e
OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels
Time frame: Baseline (Day 1e) through Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e | 78.3 Percentage of participants |
Secondary
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e
OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels
Time frame: Baseline (Day 1e) through Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e | 69.6 Percentage of participants |
Secondary
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28
OLTP Hemoglobin stabilization was defined as participants who did not receive an RBC transfusion and had no decrease in hemoglobin level of ≥2 grams per deciLiter (g/dL).
Time frame: Baseline (Day 1) through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28 | 75.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28 | 91.7 Percentage of participants |
Secondary
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e
OLEP
Time frame: Baseline (Day 1e) through week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | OLEP Baseline (Day 1e) | 87.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 8e | 83.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 16e | 82.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 24e | 82.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 32e | 86.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 40e | 82.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e | Week 52e | 82.0 Percentage of participants |
Secondary
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28
OLTP; Normalization of LDH was defined as LDH ≤1.0 × ULN at each visit
Time frame: Baseline (Day 1) through Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 1 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 10 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 4 | 83.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 12 | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Pre-treatment | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 16 | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 6 | 83.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 20 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Baseline (Day 1) | 92.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 24 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 8 | 100.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 28 | 83.0 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 2 | 92.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 28 | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 2 | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Baseline (Day 1) | 75.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Pre-treatment | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 1 | 92.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 4 | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 6 | 75.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 8 | 82.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 10 | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 12 | 83.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 16 | 75.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 20 | 92.0 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 | Week 24 | 92.0 Percentage of participants |
Secondary
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e
OLEP Not requiring a RBC transfusion as per protocol algorithm
Time frame: Baseline (Day 1e) through Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e | 87.0 Percentage of Participants |
Secondary
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e
OLEP Not requiring a RBC transfusion as per protocol algorithm
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e | 87.0 Percentage of Participants |
Secondary
Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification
OLTP No participants received dose intensification during the study; Therefore, assessment of the safety of pozelimab + cemdisiran combination therapy in participants requiring dose intensification was not conducted.
Time frame: Through Week 28
Population: Safety analysis set (SAF) included all randomized participants who received any amount of study drug and was based on the treatment received (as treated); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification | Participants with any TEAE | — |
| Unknown | Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification | Participants with any serious TEAE | — |
| Unknown | Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification | Participants with any severe TEAE | — |
Secondary
Percentage of Participants With TEAEs Up to Week 52
OLEP
Time frame: Up to Week 52
Population: The OLEP SAF includes all participants who participated in the OLEP who received any amount of study drug in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With TEAEs Up to Week 52 | Participants with any TEAE | 73.9 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With TEAEs Up to Week 52 | Participants with serious TEAE | 8.7 Percentage of participants |
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With TEAEs Up to Week 52 | Participants with severe TEAE | 4.3 Percentage of participants |
Secondary
Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28
OLTP Not requiring a red blood cell (RBC) transfusion as per protocol algorithm
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28 | 83.3 Percentage of participants |
| Pozelimab Q4W + Cemdisiran | Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28 | 100.0 Percentage of participants |
Secondary
Percent Change in CH50 From Baseline (Day 1e) to Week 16e
OLEP
Time frame: Baseline (Day 1e) to Week 16e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint; Since all participants had 0 values at baseline for CH50, the percentage change was not appropriate and undefined. Therefore, this endpoint was not able to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change in CH50 From Baseline (Day 1e) to Week 16e | NA Percentage of change |
Secondary
Percent Change in CH50 From Baseline (Day 1e) to Week 24e
OLEP
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint; Since all participants had 0 values at baseline for CH50, the percentage change was not appropriate and undefined. Therefore, this endpoint was not able to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change in CH50 From Baseline (Day 1e) to Week 24e | NA Percentage of change |
Secondary
Percent Change in CH50 From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint; Since all participants had 0 values at baseline for CH50, the percentage change was not appropriate and undefined. Therefore, this endpoint was not able to be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change in CH50 From Baseline (Day 1e) to Week 52e | NA Percentage of change |
Secondary
Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28); percentage of change in Upper Limit of Normal (xULN).
Time frame: End of treatment period, approximately 28 Weeks
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'number analyzed' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period | 2.93 Percentage of change | Standard Deviation 36.575 |
| Pozelimab Q4W + Cemdisiran | Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period | 3.65 Percentage of change | Standard Deviation 13.608 |
Secondary
Percent Change of LDH From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change of LDH From Baseline (Day 1e) to Week 52e | 0.2 Percentage of change | Standard Deviation 19.49 |
Secondary
Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e
OLEP; Percentage of change for units per liter (U/L)
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = number of evaluable participants at a specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pozelimab Q2W + Cemdisiran | Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e | -0.7 Percentage of change | Standard Deviation 20.6 |
Secondary
Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e
OLEP
Time frame: Baseline (Day 1e) to Week 24e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e | 0.591 Events per person-years of treatment |
Secondary
Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e
OLEP
Time frame: Baseline (Day 1e) to Week 52e
Population: 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 efficacy assessment in the OLEP; Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e | 0.506 Events per person-years of treatment |
Secondary
Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28
OLTP Rate of RBCs transfused is defined as number of events per person-years of treatment. For each participant, the participant-years are the time from first dose date to week 28 (or early terminations visit if subject discontinued the study early) in the OLTP.
Time frame: Baseline (Day 1) to Week 28
Population: Full analysis set (FAS) = included all randomized participants who received any amount of study drug \& had at least 1 post-baseline assessment; based on treatment allocated (as randomized); Here 'n' = the number of evaluable participants at a specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pozelimab Q2W + Cemdisiran | Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28 | 1.284 Events per person-years of treatment |
| Pozelimab Q4W + Cemdisiran | Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28 | NA Events per person-years of treatment |