Clinical Trial Results:
An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of REGN3918 in Patients with Paroxysmal Nocturnal Hemoglobinuria
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Summary
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EudraCT number |
2019-000130-20 |
Trial protocol |
NL CZ GB HU IT |
Global end of trial date |
07 Apr 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Apr 2023
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First version publication date |
20 Apr 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R3918-PNH-1868
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04162470 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Regeneron Pharmaceuticals, Inc.
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Sponsor organisation address |
777 Old Saw Mill River Road, Tarrytown, United States, 10591
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Public contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
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Scientific contact |
Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Apr 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Apr 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the long-term safety, tolerability, and effect on intravascular hemolysis of REGN3918 in participants with paroxysmal nocturnal hemoglobinuria (PNH).
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Protection of trial subjects |
It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Dec 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Hong Kong: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 12
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Country: Number of subjects enrolled |
Malaysia: 4
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Country: Number of subjects enrolled |
Taiwan: 4
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Country: Number of subjects enrolled |
United Kingdom: 2
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Worldwide total number of subjects |
24
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EEA total number of subjects |
1
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
20
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
During the study, the sponsor made an administrative decision to terminate the pozelimab monotherapy program, all participants were withdrawn from this study. | ||||||||||
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Period 1
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Period 1 title |
overall period
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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REGN3918 | ||||||||||
Arm description |
Participants who completed parent study R3918-PNH-1852 (2018-002734-20) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Pozelimab
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Investigational medicinal product code |
REGN3918
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received pozelimab 800 mg SC injection QW for up to 104 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
REGN3918
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Reporting group description |
Participants who completed parent study R3918-PNH-1852 (2018-002734-20) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
REGN3918
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Reporting group description |
Participants who completed parent study R3918-PNH-1852 (2018-002734-20) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks. | ||
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End point title |
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [1] | ||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a subject 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. Safety Analysis Set (SAF) included all enrolled participants who received any study drug.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 104
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not applicable to this endpoint. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of Participants who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26 [2] | ||||||||
End point description |
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. Full Analysis Set (FAS) included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 26
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not applicable to this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Rate of Transfusion with Red Blood Cells (RBCs) Through Week 26 | ||||||||
End point description |
The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant. FAS included all enrolled participant who received any study drug.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 26
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Had Breakthrough Hemolysis Through Week 26 and 78 | ||||||||||||
End point description |
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). FAS included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint and “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
At Week 26 and 78
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants who Achieved Adequate Control of Intravascular Hemolysis Through Week 78 | ||||||||
End point description |
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. FAS included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 78
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who are Transfusion-free (with RBCs) Through Week 26 and 78 | ||||||||||||
End point description |
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). FAS included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint and “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
At Week 26 and 78
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 | ||||||||||||
End point description |
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. FAS included all enrolled participants who received any study drug. Here, “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
At Week 26 and 78
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | ||||||||||||||
End point description |
Percent change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. FAS included all enrolled participants who received any study drug. Here, “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, 78, and 104
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Changes From Baseline in LDH Levels at Week 26, 78, and 104 | ||||||||||||||
End point description |
Change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. FAS included all enrolled participants who received any study drug. Here, “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, 78, and 104
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | ||||||||||||||
End point description |
Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported. FAS included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint and “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, 78, and 104
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | ||||||||||||||
End point description |
Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported. FAS included all enrolled participants who received any study drug. Here, “number of participants analysed” signifies participants who were evaluable for this endpoint and “n= number analysed” signifies those participants who were evaluable at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, 78 and 104
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Serum Concentrations of Total REGN3918 | ||||||||||||||||||||||||||
End point description |
Serum Concentrations of total REGN3918 was reported.
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End point type |
Secondary
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End point timeframe |
Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Number of Participants with Treatment-Emergent Anti-Drug Antibodies (ADA) to REGN3918 | ||||||||
End point description |
Number of participants with treatment-emergent ADA response to REGN3918 was reported.
Here, "number analyzed" signifies those participants who were evaluable at the specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 104
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose to Week 104
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Pozelimab
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Reporting group description |
Participants who completed parent study R3918-PNH-1852 (2018-002734-20) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks. | ||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
