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    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

    Summary
    EudraCT number
    2019-000130-20
    Trial protocol
    NL   CZ   GB   HU   IT  
    Global end of trial date
    07 Apr 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Apr 2023
    First version publication date
    20 Apr 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    R3918-PNH-1868
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04162470
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Road, Tarrytown, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    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).
    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.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Dec 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Malaysia: 4
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Worldwide total number of subjects
    24
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    20
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    During the study, the sponsor made an administrative decision to terminate the pozelimab monotherapy program, all participants were withdrawn from this study.

    Period 1
    Period 1 title
    overall period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    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
    Investigational medicinal product code
    REGN3918
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received pozelimab 800 mg SC injection QW for up to 104 weeks.

    Number of subjects in period 1
    REGN3918
    Started
    24
    Completed
    0
    Not completed
    24
         Withdrawn due to sponsor’s decision
    24

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    REGN3918
    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.

    Reporting group values
    REGN3918 Total
    Number of subjects
    24 24
    Age categorical
    Units: Participants
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    45.8 ± 17.26 -
    Gender categorical
    Units: Participants
        Female
    11 11
        Male
    13 13
    Race
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    21 21
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    0 0
        White
    2 2
        More than one race
    0 0
        Unknown or Not Reported
    1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0 0
        Not Hispanic or Latino
    24 24
        Unknown or Not Reported
    0 0

    End points

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    End points reporting groups
    Reporting group title
    REGN3918
    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.

    Primary: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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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.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 104
    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.
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Participants
        Participants with TEAEs
    15
        Participants with Serious TEAEs
    2
    No statistical analyses for this end point

    Primary: Percentage of Participants who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26

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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.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 26
    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.
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: Percentage of participants
        number (confidence interval 95%)
    95.7 (87.3 to 100.0)
    No statistical analyses for this end point

    Secondary: Overall Rate of Transfusion with Red Blood Cells (RBCs) Through Week 26

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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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Rate per person-year of treatment
        number (confidence interval 95%)
    0.164 (0.006 to 4.678)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Had Breakthrough Hemolysis Through Week 26 and 78

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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.
    End point type
    Secondary
    End point timeframe
    At Week 26 and 78
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: Percentage of participants
    number (confidence interval 95%)
        At Week 26 (n=23)
    0 (0 to 0)
        At Week 78 (n=15)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved Adequate Control of Intravascular Hemolysis Through Week 78

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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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 78
    End point values
    REGN3918
    Number of subjects analysed
    16
    Units: Percentage of participants
        number (confidence interval 95%)
    93.8 (81.9 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who are Transfusion-free (with RBCs) Through Week 26 and 78

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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.
    End point type
    Secondary
    End point timeframe
    At Week 26 and 78
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: Percentage of participants
    number (confidence interval 95%)
        At Week 26 (n=23)
    95.7 (87.3 to 100.0)
        At Week 78 (n=16)
    93.8 (81.9 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78

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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.
    End point type
    Secondary
    End point timeframe
    At Week 26 and 78
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of participants
    number (confidence interval 95%)
        At Week 26 (n=24)
    75.0 (57.7 to 92.3)
        At Week 78 (n=20)
    55.0 (33.2 to 76.8)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in LDH Levels at Week 26, 78, and 104

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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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, 78, and 104
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percent change
    arithmetic mean (standard deviation)
        At Week (n=24)
    -81.900 ± 8.9226
        At Week 78 (n=17)
    -84.256 ± 8.1412
        At Week 104 (n=15)
    -83.930 ± 7.6705
    No statistical analyses for this end point

    Secondary: Changes From Baseline in LDH Levels at Week 26, 78, and 104

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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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, 78, and 104
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Units per liter (U/L)
    arithmetic mean (standard deviation)
        At Week 26 (n=24)
    -5.098 ± 2.5695
        At Week 78 (n=17)
    -5.395 ± 2.8468
        At Week 104 (n=15)
    -5.270 ± 2.9057
    No statistical analyses for this end point

    Secondary: Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104

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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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, 78, and 104
    End point values
    REGN3918
    Number of subjects analysed
    21
    Units: Gram per liter (g/l)
    arithmetic mean (standard deviation)
        At Week 26 (n=21)
    3.6 ± 8.97
        At Week 78 (n=14)
    5.3 ± 17.20
        At Week 104 (n=5)
    -2.4 ± 16.56
    No statistical analyses for this end point

    Secondary: Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104

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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.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, 78 and 104
    End point values
    REGN3918
    Number of subjects analysed
    16
    Units: Milligram per deciliter (mg/dL)
    arithmetic mean (standard deviation)
        At Week 26 (n=16)
    -1.39 ± 6.929
        At Week 78 (n=7)
    -0.56 ± 2.196
        At Week 104 (n=4)
    -0.93 ± 1.153
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Total REGN3918

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    End point title
    Serum Concentrations of Total REGN3918
    End point description
    Serum Concentrations of total REGN3918 was reported.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: Milligrams per Liter (mg/L)
    arithmetic mean (standard deviation)
        Pre-dose (Day 1) (n=23)
    423 ± 218
        Week 13 (n=23)
    398 ± 203
        Week 26 (n=23)
    401 ± 212
        Week 39 (n=18)
    420 ± 216
        Week 52 (n = 17)
    413 ± 202
        Week 65 (n = 16)
    438 ± 207
        Week 78 (n = 10)
    433 ± 266
        Week 91 (n = 8)
    483 ± 278
        Week 104 (n = 0)
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-Emergent Anti-Drug Antibodies (ADA) to REGN3918

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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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 104
    End point values
    REGN3918
    Number of subjects analysed
    21
    Units: Participants
        Treatment-Emergent ADA
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose to Week 104
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Pozelimab
    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.

    Serious adverse events
    Pozelimab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 24 (8.33%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Pozelimab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 24 (25.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Gastrointestinal disorders
    Mouth ulceration
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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