Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
The primary objective of the study is to evaluate the long-term safety, tolerability, and effect on intravascular hemolysis of REGN3918 in patients with paroxysmal nocturnal hemoglobinuria (PNH). The secondary objectives of the study are: * To evaluate the long-term effect of REGN3918 on intravascular hemolysis * To assess the concentrations of total REGN3918 in serum * To evaluate the occurrence of the immunogenicity of REGN3918
Interventions
DRUGREGN3918
Subcutaneous (SC) every week (QW) over the treatment period
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: • Patients with PNH who have completed, without discontinuation, study treatment in one of the parent studies in which they participated (either R3918-PNH-1852 \[NCT03946748\] or R3918-PNH-1853) Key
Exclusion criteria
* Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient (for example, repetitive non-compliance with dosing by the patient) * Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study NOTE: Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to Week 104 | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs was defined as AEs that developed or worsened during the on-treatment period. SAE was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs included both Serious TEAEs and non-serious TEAEs. |
| Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26 | Baseline up to Week 26 | Percentage of participants who achieved LDH ≤1.5\* Upper limit of normal (ULN) over Week 26, defined as LDH ≤1.5\*ULN from baseline up to Week 26 were reported. A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 inclusive or through the analysis end date, whichever is earlier, had values ≤ 1.5\*ULN. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 | At Week 26 and 78 | Transfusion free was defined as not having received an RBC transfusion during the first 26 and 78 weeks. A transfusion was counted only if it was per-protocol, that is, if it follows the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level less than (\<) 9 gram per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level \< 7 g/dL (without anemia symptoms). |
| Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78 | Baseline up to Week 78 | A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of his/her LDH readings from the baseline through Week 78 inclusive or through the analysis end date, whichever is earlier, had values \<=1.5\* ULN. and must not have discontinued study treatment early. |
| Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 | Baseline, Week 26 and 78 | A participant was considered to have met normalization of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 or 78 inclusive, or through the analysis end date, whichever is earlier, had values ≤ 1.0\*ULN. |
| Changes From Baseline in LDH Levels at Week 26, 78, and 104 | Baseline, Week 26, 78, and 104 | Change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. |
| Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 | At Week 26 and 78 | A participant was considered to have breakthrough hemolysis if he/she had any LDH measurement greater than or equal to (≥) 2\*ULN, concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (i.e., LDH ≤ 1.5\* ULN). |
| Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | Baseline, Week 26, 78, and 104 | Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported. |
| Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | Baseline, Week 26, 78 and 104 | Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported. |
| Serum Concentrations of Total REGN3918 | Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104 | Serum Concentrations of total REGN3918 was reported. |
| Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918 | Baseline up to Week 104 | Number of Participants with treatment-emergent ADA response to REGN3918 was reported. The ADA analysis set (AAS) includes all treated participants who received any amount of study drug (active \[SAF\]) and had at least 1 non missing anti pozelimab antibody result following the first dose of study drug. The AAS is based on the actual treatment received (as treated). |
| Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | Baseline, Week 26, 78, and 104 | Percent change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. |
| Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26 | Baseline up to Week 26 | The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant. |
Countries
Hong Kong, Hungary, Malaysia, South Korea, Taiwan, United Kingdom
Participant flow
Pre-assignment details
During the study, the sponsor made an administrative decision to terminate the pozelimab monotherapy program, all participants were withdrawn from this study.
Participants by arm
| Arm | Count |
|---|---|
| REGN3918 Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawn due to sponsor's decision | 24 |
Baseline characteristics
| Characteristic | REGN3918 |
|---|---|
| Age, Continuous | 45.8 Years STANDARD_DEVIATION 17.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 6 / 24 |
| serious Total, serious adverse events | 2 / 24 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs was defined as AEs that developed or worsened during the on-treatment period. SAE was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time frame: Baseline up to Week 104
Population: SAF included all enrolled participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| REGN3918 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 15 Participants |
| REGN3918 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
Primary
Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26
Percentage of participants who achieved LDH ≤1.5\* Upper limit of normal (ULN) over Week 26, defined as LDH ≤1.5\*ULN from baseline up to Week 26 were reported. A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 inclusive or through the analysis end date, whichever is earlier, had values ≤ 1.5\*ULN.
Time frame: Baseline up to Week 26
Population: Full Analysis Set (FAS) included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN3918 | Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26 | 95.7 Percentage of participants |
Secondary
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104
Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported.
Time frame: Baseline, Week 26, 78 and 104
Population: FAS included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN3918 | Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | At Week 26 | -1.39 Milligram per deciliter (mg/dL) | Standard Deviation 6.929 |
| REGN3918 | Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | At Week 78 | -0.56 Milligram per deciliter (mg/dL) | Standard Deviation 2.196 |
| REGN3918 | Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | At Week 104 | -0.93 Milligram per deciliter (mg/dL) | Standard Deviation 1.153 |
Secondary
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104
Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported.
Time frame: Baseline, Week 26, 78, and 104
Population: FAS included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN3918 | Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | At Week 26 | 3.6 Gram per liter (g/l) | Standard Deviation 8.97 |
| REGN3918 | Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | At Week 78 | 5.3 Gram per liter (g/l) | Standard Deviation 17.2 |
| REGN3918 | Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | At Week 104 | -2.4 Gram per liter (g/l) | Standard Deviation 16.56 |
Secondary
Changes From Baseline in LDH Levels at Week 26, 78, and 104
Change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study.
Time frame: Baseline, Week 26, 78, and 104
Population: FAS included all enrolled participants who received any study drug. Here, number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN3918 | Changes From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 26 | -5.098 Units per liter (U/L) | Standard Deviation 2.5695 |
| REGN3918 | Changes From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 78 | -5.395 Units per liter (U/L) | Standard Deviation 2.8468 |
| REGN3918 | Changes From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 104 | -5.270 Units per liter (U/L) | Standard Deviation 2.9057 |
Secondary
Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918
Number of Participants with treatment-emergent ADA response to REGN3918 was reported. The ADA analysis set (AAS) includes all treated participants who received any amount of study drug (active \[SAF\]) and had at least 1 non missing anti pozelimab antibody result following the first dose of study drug. The AAS is based on the actual treatment received (as treated).
Time frame: Baseline up to Week 104
Population: Here, number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REGN3918 | Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918 | 0 Participants |
Secondary
Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26
The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Time frame: Baseline up to Week 26
Population: FAS included all enrolled participants who received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN3918 | Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26 | 0.164 Transfusion per person-year of treatment |
Secondary
Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78
A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of his/her LDH readings from the baseline through Week 78 inclusive or through the analysis end date, whichever is earlier, had values \<=1.5\* ULN. and must not have discontinued study treatment early.
Time frame: Baseline up to Week 78
Population: FAS included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN3918 | Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78 | 93.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78
A participant was considered to have met normalization of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 or 78 inclusive, or through the analysis end date, whichever is earlier, had values ≤ 1.0\*ULN.
Time frame: Baseline, Week 26 and 78
Population: FAS included all enrolled participants who received any study drug. Here, number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| REGN3918 | Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 | At Week 26 | 75.0 Percentage of participants |
| REGN3918 | Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 | At Week 78 | 55.0 Percentage of participants |
Secondary
Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78
Transfusion free was defined as not having received an RBC transfusion during the first 26 and 78 weeks. A transfusion was counted only if it was per-protocol, that is, if it follows the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level less than (\<) 9 gram per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level \< 7 g/dL (without anemia symptoms).
Time frame: At Week 26 and 78
Population: FAS included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| REGN3918 | Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 | At Week 26 | 95.7 Percentage of participants |
| REGN3918 | Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 | At Week 78 | 93.8 Percentage of participants |
Secondary
Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78
A participant was considered to have breakthrough hemolysis if he/she had any LDH measurement greater than or equal to (≥) 2\*ULN, concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (i.e., LDH ≤ 1.5\* ULN).
Time frame: At Week 26 and 78
Population: FAS included all enrolled participants who received any study drug. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| REGN3918 | Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 | At Week 26 | 0 Percentage of participants |
| REGN3918 | Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 | At Week 78 | 0 Percentage of participants |
Secondary
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104
Percent change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study.
Time frame: Baseline, Week 26, 78, and 104
Population: FAS included all enrolled participants who received any study drug. Here, number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN3918 | Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 26 | -81.900 Percent change | Standard Deviation 8.9226 |
| REGN3918 | Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 78 | -84.256 Percent change | Standard Deviation 8.1412 |
| REGN3918 | Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | At Week 104 | -83.930 Percent change | Standard Deviation 7.6705 |
Secondary
Serum Concentrations of Total REGN3918
Serum Concentrations of total REGN3918 was reported.
Time frame: Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104
Population: Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN3918 | Serum Concentrations of Total REGN3918 | Pre-dose (Day 1) | 423 Milligrams per liter (mg/L) | Standard Deviation 218 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 13 | 398 Milligrams per liter (mg/L) | Standard Deviation 203 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 26 | 401 Milligrams per liter (mg/L) | Standard Deviation 212 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 39 | 420 Milligrams per liter (mg/L) | Standard Deviation 216 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 52 | 413 Milligrams per liter (mg/L) | Standard Deviation 202 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 65 | 438 Milligrams per liter (mg/L) | Standard Deviation 207 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 78 | 433 Milligrams per liter (mg/L) | Standard Deviation 266 |
| REGN3918 | Serum Concentrations of Total REGN3918 | Week 91 | 483 Milligrams per liter (mg/L) | Standard Deviation 278 |