Trial Outcomes & Findings for Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy (NCT NCT04888507)
NCT ID: NCT04888507
Last Updated: 2025-08-29
Results Overview
COMPLETED
PHASE2
6 participants
Up to Day 225
2025-08-29
Participant Flow
A total of 7 participants were screened and 6 were enrolled and received study treatment.
Participant milestones
| Measure |
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)
|
|---|---|
|
Open-Label Treatment (OLTP) (32 Weeks)
STARTED
|
6
|
|
Open-Label Treatment (OLTP) (32 Weeks)
COMPLETED
|
5
|
|
Open-Label Treatment (OLTP) (32 Weeks)
NOT COMPLETED
|
1
|
|
Open-Label Extension (OLEP) (52 Weeks)
STARTED
|
5
|
|
Open-Label Extension (OLEP) (52 Weeks)
COMPLETED
|
5
|
|
Open-Label Extension (OLEP) (52 Weeks)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
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)
|
|---|---|
|
Open-Label Treatment (OLTP) (32 Weeks)
Adverse Event
|
1
|
Baseline Characteristics
Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy
Baseline characteristics by cohort
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
Age, Continuous
|
51.3 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Day 225Population: The safety analysis set included all participants who received any amount of study drug.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
6 Participants
|
SECONDARY outcome
Timeframe: Screening (Day 1) through Day 225Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
|
-0.95 percent change
Standard Deviation 13.40
|
SECONDARY outcome
Timeframe: Screening (Day 1) through Day 29Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percent Change in LDH From Pre-treatment Through Day 29
|
3.61 percent change
Standard Deviation 35.99
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32
|
0 transfusions per person-year
Not calculable due to insufficient number of events.
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Rate of RBC Transfusions From Week 4 Through Week 32
|
0 transfusions per person-year
Not calculable due to insufficient number of events.
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of RBC Units Transfused From Baseline Through Week 32
|
0 RBC units
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of RBC Units Transfused From Week 4 Through Week 32
|
0 RBC units
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Breakthrough hemolysis was defined as having an LDH ≥ 2 x upper limit of normal (ULN) and having signs or symptoms.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Adequate control was defined as LDH ≤ 1.5 x ULN from Day 1 through Week 32.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32
|
83.3 percentage of participants
Interval 53.5 to 100.0
|
SECONDARY outcome
Timeframe: Week 8 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Adequate control was defined as LDH ≤ 1.5 x ULN from Week 8 through Week 32.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32
|
83.3 percentage of participants
Interval 53.5 to 100.0
|
SECONDARY outcome
Timeframe: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225Population: 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.
Adequate control at a visit was defined as having LDH ≤1.5 x ULN at that visit.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 225
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 1
|
6 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 8
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 15
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 29
|
6 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 43
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 57
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 71
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 85
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 113
|
4 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 141
|
5 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 169
|
4 Participants
|
|
OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit
Day 197
|
3 Participants
|
SECONDARY outcome
Timeframe: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225Population: 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.
Normalization was defined as LDH ≤ 1.0 x ULN at that visit.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 1
|
6 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 8
|
5 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 15
|
5 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 29
|
6 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 43
|
5 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 57
|
4 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 71
|
5 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 85
|
4 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 113
|
4 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 141
|
5 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 169
|
4 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 197
|
3 Participants
|
|
OLTP: Number of Participants With Normalization of Their LDH at Each Visit
Day 225
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Average LDH From Baseline Through Week 32
|
227.34 Units per Liter (U/L)
Standard Deviation 45.08
|
SECONDARY outcome
Timeframe: Week 8 through Week 32Population: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Average LDH From Week 8 Through Week 32
|
223.49 U/L
Standard Deviation 49.01
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 grams per deciliter (g/dL).
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: The FAS included all enrolled participants who received any amount of study drug and had at least 1 post-baseline assessment.
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline, Week 32Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Change From Baseline in Hemoglobin Levels
|
0.54 g/dL
Standard Deviation 0.60
|
SECONDARY outcome
Timeframe: Baseline, Week 32Population: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=1 Participants
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)
|
|---|---|
|
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 outcome
Timeframe: Baseline, Week 32Population: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=1 Participants
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)
|
|---|---|
|
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 outcome
Timeframe: Baseline, Week 32Population: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=1 Participants
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)
|
|---|---|
|
OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30
|
6.667 score on a scale
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: 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.
This assay assessed the activity of the classical pathway of complement to measure C5 activity.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50)
|
0.0 International units per mL (IU/mL)
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: Pre-dose Days 28, 56, 84, 112, 140, 168, 196, 224, 392, 588; Post-dose Day 28Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 28
|
0 milligrams per liter (mg/L)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
15 Minutes Post-dose Day 28
|
1280 milligrams per liter (mg/L)
Standard Deviation 193
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 56
|
333 milligrams per liter (mg/L)
Standard Deviation 48.1
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 84
|
189 milligrams per liter (mg/L)
Standard Deviation 54.8
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 112
|
121 milligrams per liter (mg/L)
Standard Deviation 57.2
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 140
|
102 milligrams per liter (mg/L)
Standard Deviation 40.7
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 168
|
70.1 milligrams per liter (mg/L)
Standard Deviation 37.3
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 196
|
86.1 milligrams per liter (mg/L)
Standard Deviation 36.6
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 224
|
71.7 milligrams per liter (mg/L)
Standard Deviation 41.4
|
|
OLTP and OLEP: Concentration of Total Pozelimab in Serum
Pre-dose Day 392
|
53.1 milligrams per liter (mg/L)
Standard Deviation 25.6
|
|
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 outcome
Timeframe: Pre-dose Days 0, 14, 28, 56, 84, 112, 140, 168, 196, 224Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 28
|
242 mg/L
Standard Deviation 59.0
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 0
|
231 mg/L
Standard Deviation 64.5
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 14
|
225 mg/L
Standard Deviation 63.2
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 56
|
101 mg/L
Standard Deviation 42.9
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 84
|
44.4 mg/L
Standard Deviation 38.7
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 112
|
22.5 mg/L
Standard Deviation 29.5
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 140
|
12.6 mg/L
Standard Deviation 12.5
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 168
|
4.23 mg/L
Standard Deviation 6.46
|
|
OLTP: Concentration of Total Eculizumab in Serum
Pre-dose Day 224
|
0.540 mg/L
Standard Deviation 1.16
|
SECONDARY outcome
Timeframe: Pre-dose and Post-dose Days 0, 84, 196, 224, 588Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Pre-dose Day 0
|
0 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Post-dose Day 0
|
139 nanograms per milliliter (ng/mL)
Standard Deviation 45.5
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Pre-dose Day 84
|
0 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Post-dose Day 84
|
178 nanograms per milliliter (ng/mL)
Standard Deviation 111
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Pre-dose Day 196
|
0 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Post-dose Day 196
|
196 nanograms per milliliter (ng/mL)
Standard Deviation 100
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Pre-dose Day 224
|
0 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Post-dose Day 224
|
158 nanograms per milliliter (ng/mL)
Standard Deviation 75.7
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Pre-dose Day 588
|
0 nanograms per milliliter (ng/mL)
Standard Deviation 0
|
|
OLTP and OLEP: Concentration of Total Cemdisiran in Plasma
Post-dose Day 588
|
215 nanograms per milliliter (ng/mL)
Standard Deviation 84.8
|
SECONDARY outcome
Timeframe: Pre-dose Days 0, 7, 14, 28, 56, 84, 112, 140, 168, 196, 224, 392, 588Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 0
|
320 mg/L
Standard Deviation 64.2
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-Dose Day 7
|
191 mg/L
Standard Deviation 46.2
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 14
|
118 mg/L
Standard Deviation 28.0
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 28
|
54.5 mg/L
Standard Deviation 14.2
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 56
|
2.77 mg/L
Standard Deviation 6.78
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 84
|
2.90 mg/L
Standard Deviation 6.48
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 112
|
3.88 mg/L
Standard Deviation 7.75
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 140
|
3.10 mg/L
Standard Deviation 6.93
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 168
|
4.79 mg/L
Standard Deviation 7.18
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 196
|
2.03 mg/L
Standard Deviation 4.05
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 224
|
4.96 mg/L
Standard Deviation 7.44
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 392
|
5.02 mg/L
Standard Deviation 7.13
|
|
OLTP and OLEP: Concentration of Total C5 in Plasma
Pre-dose Day 588
|
5.28 mg/L
Standard Deviation 7.44
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA)
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: 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.
Outcome measures
| Measure |
Participants With PNH
n=6 Participants
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)
|
|---|---|
|
OLTP: Number of Participants With Cemdisiran ADA
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline through Week 32Population: No participants required treatment intensification during the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: The OLEP safety analysis set included all participants who participated in the OLEP who received any amount of study drug in the OLEP.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of Participants With TEAEs
|
5 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP
|
-6.17 percent change
Standard Deviation 9.15
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP
|
-3.46 percent change
Standard Deviation 10.94
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP
|
80.0 percentage of participants
Interval 44.9 to 100.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP
|
0 transfusions per person-year
Not calculable due to insufficient number of events.
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP
|
0.200 transfusions per person-year
Interval 0.028 to 1.421
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP
|
0 RBC units
Standard Deviation 0.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP
|
0.4 RBC units
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Adequate control was defined as LDH ≤ 1.5 x ULN.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Adequate control was defined as LDH ≤ 1.5 x ULN.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEPPopulation: 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.
Adequate control was defined as LDH ≤ 1.5 x ULN at that visit.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Baseline OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 57 OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 113 OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 169 OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 225 OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 281 OLEP
|
5 Participants
|
|
OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP
Day 365 OLEP
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEPPopulation: 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.
Normalization was defined as LDH ≤ 1.0 x ULN at that visit.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Baseline OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 57 OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 113 OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 169 OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 225 OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 281 OLEP
|
5 Participants
|
|
OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP
Day 365 OLEP
|
4 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Average LDH From Day 1 Through Week 24 of the OLEP
|
210.55 U/L
Standard Deviation 42.64
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Average LDH From Day 1 Through Week 52 of the OLEP
|
210.13 U/L
Standard Deviation 44.91
|
SECONDARY outcome
Timeframe: Day 1 through Week 24 of the OLEPPopulation: 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.
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP
|
100 percentage of participants
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP
|
80.0 percentage of participants
Interval 44.9 to 100.0
|
SECONDARY outcome
Timeframe: Day 1 and Week 24 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Change From Baseline in Hemoglobin Levels
|
-0.10 g/dL
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: Day 1 and Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Change From Baseline in Hemoglobin Levels
|
0.16 g/dL
Standard Deviation 0.70
|
SECONDARY outcome
Timeframe: Day 1 and Week 52 of the OLEPPopulation: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Change From Baseline in FACIT-Fatigue Score
|
-2.4 score on a scale
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Day 1 and Week 52 of the OLEPPopulation: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
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 outcome
Timeframe: Day 1 and Week 52 of the OLEPPopulation: 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.
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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30
|
0.000 score on a scale
Standard Deviation 4.714
|
SECONDARY outcome
Timeframe: Baseline, Week 16, Week 32, Week 52 of the OLEPPopulation: 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.
This assay assessed the activity of the classical pathway of complement to measure C5 activity.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Change From Baseline in CH50
Change at Week 16
|
0.0 IU/mL
Standard Deviation 0.0
|
|
OLEP: Change From Baseline in CH50
Change at Week 32
|
0.6 IU/mL
Standard Deviation 1.3
|
|
OLEP: Change From Baseline in CH50
Change at Week 52
|
1.2 IU/mL
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of Participants With Pozelimab ADA
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Week 52 of the OLEPPopulation: 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.
Outcome measures
| Measure |
Participants With PNH
n=5 Participants
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)
|
|---|---|
|
OLEP: Number of Participants With Cemdisiran ADA
|
0 Participants
|
Adverse Events
OLTP: Participants With PNH
OLEP: Participants With PNH
Serious adverse events
| Measure |
OLTP: Participants With PNH
n=6 participants at risk
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)
|
OLEP: Participants With PNH
n=5 participants at risk
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)
|
|---|---|---|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
Other adverse events
| Measure |
OLTP: Participants With PNH
n=6 participants at risk
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)
|
OLEP: Participants With PNH
n=5 participants at risk
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)
|
|---|---|---|
|
Infections and infestations
COVID-19
|
33.3%
2/6 • Number of events 2 • From signing informed consent up to 84 weeks
|
40.0%
2/5 • Number of events 2 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Injection site infection
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
40.0%
2/5 • Number of events 3 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Skin candida
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Vulvovaginal candidiasis
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Nervous system disorders
Headache
|
50.0%
3/6 • Number of events 4 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Nervous system disorders
Lethargy
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Nervous system disorders
Memory impairment
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
2/6 • Number of events 2 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Ear and labyrinth disorders
Tinnitus
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Eye disorders
Ocular hyperaemia
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Gastrointestinal disorders
Dysphagia
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Injury, poisoning and procedural complications
Muscle strain
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
Skin and subcutaneous tissue disorders
Skin burning sensation
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
40.0%
2/5 • Number of events 2 • From signing informed consent up to 84 weeks
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/6 • From signing informed consent up to 84 weeks
|
20.0%
1/5 • Number of events 1 • From signing informed consent up to 84 weeks
|
|
General disorders
Fatigue
|
16.7%
1/6 • Number of events 1 • From signing informed consent up to 84 weeks
|
0.00%
0/5 • From signing informed consent up to 84 weeks
|
|
General disorders
Injection site reaction
|
83.3%
5/6 • Number of events 22 • From signing informed consent up to 84 weeks
|
60.0%
3/5 • Number of events 4 • From signing informed consent up to 84 weeks
|
Additional Information
Clinical Trials Administrator
Regeneron Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the Sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER