Phase 2
N=24
Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
Paroxysmal Nocturnal Hemoglobinuria
Bottom Line
View on ClinicalTrials.gov: NCT04811716 ↗Enrolled (actual)
24
Serious AEs
10.6%
Results posted
Jan 2025
Primary outcome: Primary: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) — 66.7; 41.7; 16.7; 0 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Pozelimab (Drug); Cemdisiran (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Oct 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
66.7; 41.7; 16.7; 0; 16.7; 0 | — |
| SECONDARY Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period |
2.93; 3.65 | — |
| SECONDARY Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28 |
75.0; 91.7 | — |
| SECONDARY Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28 |
83.3; 91.7 | — |
| SECONDARY Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28 |
100.0; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28 |
92.0; 75.0; 92.0; 83.0; 100.0; 92.0 | — |
| SECONDARY Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28 |
238.18; 244.42 | — |
| SECONDARY Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28 |
202.49; 211.28 | — |
| SECONDARY Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28 |
8.3; 0.0 | — |
| SECONDARY Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28 |
75.0; 91.7 | — |
| SECONDARY Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28 |
-1.3; 10.3 | — |
| SECONDARY Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28 |
83.3; 100.0 | — |
| SECONDARY Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28 |
1.284; NA | — |
| SECONDARY Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28 |
1.5; 0.0 | — |
| SECONDARY Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28 |
0.0; -0.1 | — |
| SECONDARY 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; -2.0 | — |
| 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 |
-9.4; -1.9 | — |
| SECONDARY Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28 |
-6.7; 0.7 | — |
| SECONDARY Concentrations of Total Pozelimab in Serum on Week 28 |
131; 58.2 | — |
| SECONDARY Concentrations of Cemdisiran in Plasma on Week 28 |
NA; NA | — |
| SECONDARY Concentrations of Total C5 on Week 28 |
0; 0 | — |
| SECONDARY Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time |
0; 0; 0; 1 | — |
| SECONDARY Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification |
— | — |
| SECONDARY Change of LDH From Baseline (Day 1e) to Week 24e |
-18.2 | — |
| SECONDARY Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e |
-0.7 | — |
| SECONDARY Change of LDH From Baseline (Day 1e) to Week 52e |
-14.5 | — |
| SECONDARY Percent Change of LDH From Baseline (Day 1e) to Week 52e |
0.2 | — |
| SECONDARY Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e |
95.7 | — |
| SECONDARY Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e |
95.7 | — |
| SECONDARY Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e |
96.0; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e |
87.0; 83.0; 82.0; 82.0; 86.0; 82.0 | — |
| SECONDARY Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e |
154.63 | — |
| SECONDARY Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e |
4.3 | — |
| SECONDARY Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e |
4.3 | — |
| SECONDARY Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e |
78.3 | — |
| SECONDARY Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e |
69.6 | — |
| SECONDARY Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e |
0.8 | — |
| SECONDARY Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e |
-0.6 | — |
| SECONDARY Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e |
87.0 | — |
| SECONDARY Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e |
87.0 | — |
| SECONDARY Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e |
0.591 | — |
| SECONDARY Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e |
0.506 | — |
| SECONDARY Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e |
0.4 | — |
| SECONDARY Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e |
0.9 | — |
| SECONDARY Change in CH50 From Baseline (Day 1e) to Week 16e |
0.0 | — |
| SECONDARY Change in CH50 From Baseline (Day 1e) to Week 24e |
— | — |
| SECONDARY Change in CH50 From Baseline (Day 1e) to Week 52e |
0.0 | — |
| SECONDARY Percent Change in CH50 From Baseline (Day 1e) to Week 16e |
NA | — |
| SECONDARY Percent Change in CH50 From Baseline (Day 1e) to Week 24e |
NA | — |
| SECONDARY Percent Change in CH50 From Baseline (Day 1e) to Week 52e |
NA | — |
| SECONDARY 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 | — |
| SECONDARY Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e |
6.0 | — |
| SECONDARY Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e |
-0.3 | — |
| SECONDARY Percentage of Participants With TEAEs Up to Week 52 |
73.9; 8.7; 4.3 | — |
| SECONDARY Concentrations of Total Pozelimab in Serum on Week 52 |
63.4; 58.6 | — |
| SECONDARY Concentrations of Total C5 on Week 52 |
0; NA | — |
| SECONDARY Concentrations of Cemdisiran in Plasma on Week 52 |
NA; NA | — |
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
Eligibility Criteria
Key Inclusion Criteria
- Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)
Key Exclusion Criteria
- 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
- 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
- Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
- 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
- Known hypersensitivity to cemdisiran or any component of cemdisiran formulation
NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
Data sourced from ClinicalTrials.gov (NCT04811716). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.