Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43850   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Open Label, Single Arm Study to Evaluate the Efficacy and Safety of REGN3918 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor Naive or Have Not Recently Received Complement Inhibitor Therapy

    Summary
    EudraCT number
    2018-002734-20
    Trial protocol
    CZ   GB   HU   NL   IT  
    Global end of trial date
    10 Jun 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Jun 2022
    First version publication date
    24 Jun 2022
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    R3918-PNH-1852
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03946748
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., 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
    10 Jun 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jun 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in subjects with active PNH who are treatment naive to complement inhibitor therapy or have not recently received complement inhibitor therapy.
    Protection of trial subjects
    It was the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study was 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
    16 May 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
    United Kingdom: 2
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Malaysia: 4
    Country: Number of subjects enrolled
    Taiwan: 4
    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

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Sponsor made administrative decision to stop enrollment to pursue combination program of REGN3918 & cemdisiran for treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). Study not stopped due to safety concerns or lack of efficacy. 28 screened, 24 were enrolled & treated: 4 screen failures (1-Lost to follow-up, 1-did not meet criteria, 1-other).

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

    Arms
    Arm title
    REGN3918
    Arm description
    Participants received a single loading dose of REGN3918 30 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1, followed by a maintenance regimen of 800 milligrams (mg) subcutaneous (SC) injection on Day 8 once weekly (QW) up to 26 weeks of treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Pozelimab
    Investigational medicinal product code
    REGN3918
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received REGN3918 30 mg/kg IV infusion, followed by a maintenance regimen of 800 mg SC injection up to 26 weeks of treatment period.

    Number of subjects in period 1
    REGN3918
    Started
    24
    Completed
    24

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall study
    Reporting group description
    Participants received a single loading dose of REGN3918 30 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1, followed by a maintenance regimen of 800 milligrams (mg) subcutaneous (SC) injection on Day 8 once weekly (QW) up to 26 weeks of treatment period.

    Reporting group values
    Overall study Total
    Number of subjects
    24 24
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    45.4 ( 17.28 ) -
    Gender categorical
    Units: Subjects
        Female
    11 11
        Male
    13 13
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 0
        Not Hispanic or Latino
    24 24
        Unknown or Not Reported
    0 0
    Race (NIH/OMB)
    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

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    REGN3918
    Reporting group description
    Participants received a single loading dose of REGN3918 30 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1, followed by a maintenance regimen of 800 milligrams (mg) subcutaneous (SC) injection on Day 8 once weekly (QW) up to 26 weeks of treatment period.

    Primary: Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis

    Close Top of page
    End point title
    Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis [1]
    End point description
    Participants were considered to have had adequate control of intravascular hemolysis if all of their lactose dehydrogenase (LDH) readings from Week 4 through Week 26 inclusive had values less than or equal to ≤ 1.5 × upper limit of normal (ULN). Participants must have more than equal to (≥) 50 percent (%) of scheduled LDH measures in those weeks, must not have had more than (>) 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. Participants were considered not to have had adequate control of intravascular hemolysis if they failed any of these criteria. Full analysis set (FAS) included all enrolled participants who received any study drug.
    End point type
    Primary
    End point timeframe
    Week 4 through Week 26
    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: Results were descriptively summarized.
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of Participants
        number (confidence interval 95%)
    75.0 (57.7 to 92.3)
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Achieved Transfusion Avoidance

    Close Top of page
    End point title
    Percentage of Participants Who Achieved Transfusion Avoidance [2]
    End point description
    Transfusion avoidance was defined as not having received red blood cell (RBC) transfusion during the first 26 weeks. A transfusion was counted only if it is per-protocol, that is, it follows the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level < 9 grams per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level < 7 g/dL (without anemia symptoms). The FAS included all enrolled participants who received any study drug.
    End point type
    Primary
    End point timeframe
    Up to 26 Weeks
    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: Results were descriptively summarized.
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of Participants
        number (confidence interval 95%)
    87.5 (74.3 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Had Breakthrough Hemolysis (BTH)

    Close Top of page
    End point title
    Percentage of Participants Who Had Breakthrough Hemolysis (BTH)
    End point description
    Breakthrough hemolysis was defined as the measurement of LDH ≥ 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). The FAS included all enrolled subjects who received any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to 26 Weeks
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of Participants
        number (confidence interval 95%)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis

    Close Top of page
    End point title
    Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis
    End point description
    A participant was considered to have achieved normalization of intravascular hemolysis if their LDH readings between Week 4 through Week 26 inclusive had values ≤ 1.0 ULN. A participant must have ≥ 50% of scheduled LDH measures in those weeks, must not have had > 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. A participant was considered not to have achieved normalization of intravascular hemolysis if they failed any of these criteria. The FAS included all enrolled participants who received any study drug.
    End point type
    Secondary
    End point timeframe
    Week 4 through Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of Participants
        number (confidence interval 95%)
    16.7 (1.8 to 31.6)
    No statistical analyses for this end point

    Secondary: Time to First Lactate Dehydrogenase (LDH) ≤ 1.5 x ULN

    Close Top of page
    End point title
    Time to First Lactate Dehydrogenase (LDH) ≤ 1.5 x ULN
    End point description
    A time-to-first-event analysis was used to estimate the proportion of participants achieving transfusion avoidance at week 26 and a 95% confidence interval. As per changes in planned analysis, the sponsor made an administrative decision to close enrollment for this study due to a change in the clinical development program. Hence, this endpoint was not analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    0 [3]
    Units: Weeks
        median (full range (min-max))
    ( to )
    Notes
    [3] - Sponsor made administrative decision to close enrollment. Hence, this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26

    Close Top of page
    End point title
    Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26
    End point description
    Percentage of days was calculated as number of days with LDH ≤ 1.5 x ULN divided by the participants' total treatment duration (total number of days on treatment from Week 4 through Week 26). LDH ≤ 1.5 x ULN was used as an indicator of adequate control of intravascular hemolysis. The FAS included all enrolled participants who received any study drug.
    End point type
    Secondary
    End point timeframe
    Week 4 through Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percentage of Days
        arithmetic mean (standard deviation)
    93.4 ( 18.76 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in LDH Levels at Week 26

    Close Top of page
    End point title
    Change From Baseline in LDH Levels at Week 26
    End point description
    Change from baseline in LDH levels at Week 26 was reported. The FAS included all enrolled participants who received any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Units per liter (U/L)
        least squares mean (standard error)
    -5.070 ( 0.1467 )
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in LDH Levels at Week 26

    Close Top of page
    End point title
    Percent Change From Baseline in LDH Levels at Week 26
    End point description
    Percent change from baseline in LDH levels at Week 26 was reported. The FAS included all enrolled participants who received any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Percent Change
        least squares mean (standard error)
    -81.72 ( 1.847 )
    No statistical analyses for this end point

    Secondary: Rate of Transfusion With Red Blood Cells (RBCs)

    Close Top of page
    End point title
    Rate of Transfusion With Red Blood Cells (RBCs)
    End point description
    The rate of transfusion with RBCs for a participant was the total number of transfusions divided by total person-years of time on treatment. The FAS included all enrolled participants 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: Infusions Per Participant Year
        number (confidence interval 95%)
    1.039 (0.187 to 5.772)
    No statistical analyses for this end point

    Secondary: Number of Units of Transfusion With RBCs

    Close Top of page
    End point title
    Number of Units of Transfusion With RBCs
    End point description
    Transfusions with RBCs proceeded according to the following predefined criteria that triggered a transfusion; however, the actual number of units to be transfused is at the discretion of the investigator: • Transfuse with RBC(s) if the post-baseline hemoglobin level is <9 g/dL with symptoms resulting from anemia or • Transfuse with RBC(s) if the post-baseline hemoglobin level is <7 g/dL. As per changes in planned analysis, the sponsor made an administrative decision to close enrollment for this study due to a change in the clinical development program. Hence, this endpoint was not analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    0 [4]
    Units: Number of Units
        number (not applicable)
    Notes
    [4] - Sponsor made administrative decision to close enrollment. Hence, this endpoint was not analyzed.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Free Hemoglobin Levels at Week 26

    Close Top of page
    End point title
    Change From Baseline in Free Hemoglobin Levels at Week 26
    End point description
    Change from baseline in free hemoglobin levels at Week 26 was assessed. The safety analysis set (SAF) included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    22
    Units: milligrams per Deciliter (mg/dL)
        arithmetic mean (standard deviation)
    -9.19 ( 16.264 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in RBC Hemoglobin Levels at Week 26

    Close Top of page
    End point title
    Change From Baseline in RBC Hemoglobin Levels at Week 26
    End point description
    Hemoglobin levels in participants with PNH was measured. Change from baseline in RBC hemoglobin at Week 26 was reported. The FAS included all enrolled participants who received any study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: grams per Liter (g/L)
        least squares mean (standard error)
    15.0 ( 3.24 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) at Week 26

    Close Top of page
    End point title
    Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) at Week 26
    End point description
    Change from baseline in total CH50 at Week 26 was reported. Here “International units per milliliter” was abbreviated as “IU/mL”. The FAS included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: IU/mL
        least squares mean (standard error)
    -236.6 ( 0.65 )
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in CH50 up to Week 26

    Close Top of page
    End point title
    Percent Change From Baseline in CH50 up to Week 26
    End point description
    Percent change from baseline in CH50 up to Week 26 was reported. The FAS included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    23
    Units: Percent Change
    least squares mean (standard error)
        Percent Change From Baseline in CH50
    -99.99 ( 0.243 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 26

    Close Top of page
    End point title
    Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 26
    End point description
    The FACIT-F was a 13-item, self-reported PRO measure assessing an individual’s level of fatigue during their usual daily activities over the past week. This questionnaire was part of the FACIT measurement system, a compilation of questions measuring health-related QoL in participants with cancer and other chronic illnesses. The FACIT-fatigue assessed the level of fatigue using a 4-point Likert scale ranging from 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much) The sum of all responses resulted in the FACIT-F score for a total possible score of 0 to 52, with higher scores indicated greater fatigue. FAS population. Here, “number of subjects analyzed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    22
    Units: Score on a Scale
        least squares mean (standard error)
    9.9 ( 1.52 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) at Week 26

    Close Top of page
    End point title
    Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) at Week 26
    End point description
    EORTC QLQ-C30 was a 30-item questionnaire used to assess symptoms & side effects of treatment. It consists of 15 domains: 5 multi-item functioning scales (physical, role, social, emotional & cognitive), answered on 4-point scale (1=Not at all,2=A Little,3=Quite a Bit,4=Very Much). Each score ranges: 0-100; higher score indicates higher level of functioning & better QoL. A global health status/QoL scale answered on 7-point scale (1=Very Poor to 7=Excellent). Each score ranges: 0-100; higher score indicates better QoL. 9 symptom scales (Fatigue, Nausea/Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, Financial Impact), answered on 4-point scale (1=Not at all, 2=A Little, 3=Quite a Bit, 4=Very Much). Each score ranges:0-100; higher score indicates higher level of symptoms, & negative change from baseline indicates an improvement in symptoms. FAS population. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    22
    Units: Score on a Scale
    least squares mean (standard error)
        Global Health status/quality: Change at Week 26
    12.509 ( 3.2286 )
        Physical Functioning: Change at Week 26
    17.511 ( 2.6767 )
        Cognitive Functioning: Change at Week 26
    9.840 ( 2.9710 )
        Social Functioning: Change at Week 26
    15.846 ( 3.8036 )
        Fatigue: Change at Week 26
    -18.904 ( 2.9899 )
        Pain: Change at Week 26
    -13.537 ( 3.0315 )
        Dyspnea: Change at Week 26
    -15.874 ( 4.7953 )
        Emotional Functioning: Change at Week 26
    14.457 ( 3.8645 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Index Score at Week 26

    Close Top of page
    End point title
    Change From Baseline in European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Index Score at Week 26
    End point description
    EQ-5D-3L was a self-administered standardized instrument for use as measure of health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension rated on 3 levels scale: 1 (no problems), 2 (some problems), 3 (extreme problems). The summed score ranges from 5-15 with “5” corresponding to no problems and “15” to severe problems in 5 dimensions. EQ-5D index calculated by applying preference-based weights (tariffs) to scores of five health state dimensions. Index values range from -1 to 1, with 0 representing a health state equivalent to death and 1 representing perfect health. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). FAS included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    22
    Units: Score on a Scale
        least squares mean (standard error)
    0.136 ( 0.0238 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Week 26

    Close Top of page
    End point title
    Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Week 26
    End point description
    The EQ-5D-3L was a standardized instrument for use as a measure of health outcome and was administered to all subjects to assess the effect of the treatment on the participants’ quality of life. The EQ-5D-3L includes a visual analog scale (VAS) which is a vertical scale with numbers ranging from 0 to 100. Participants were asked to draw a line to the place on the scale that best represented how good or bad his health was on that day. The worst state a participant can imagine was marked zero, and the best state the participant can imagine was marked 100. Mean change in VAS score from baseline was reported. The FAS included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    REGN3918
    Number of subjects analysed
    22
    Units: Score on a Scale
        least squares mean (standard error)
    8.4 ( 2.18 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    Close Top of page
    End point title
    Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
    End point description
    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. The SAF included all enrolled participants 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: Participants
        Participants with TEAEs
    21
        Participants with Serious TEAEs
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs Based on Severity

    Close Top of page
    End point title
    Number of Participants With TEAEs Based on Severity
    End point description
    An 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. Severity of AEs was graded according to the following scale, Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention. The SAF included all enrolled participants who received any study drug. Here, “number of subjects analysed” signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    21
    Units: Participants
        Participants with Mild TEAEs
    13
        Participants with Moderate TEAEs
    6
        Participants with Severe TEAEs
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters

    Close Top of page
    End point title
    Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters
    End point description
    Clinical laboratory parameters included biochemistry, hematology and urinalysis. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically significant by the investigator were reported. The SAF included all enrolled participants 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: Participants
        Hematology
    13
        Chemistry
    17
        Urinalysis
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Meaningful Changes in 12-lead Electrocardiograms (ECGs)

    Close Top of page
    End point title
    Number of Participants With Clinically Meaningful Changes in 12-lead Electrocardiograms (ECGs)
    End point description
    12-lead ECGs were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported. The FAS included all enrolled participants 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: Participants
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Meaningful Changes in Vital Signs

    Close Top of page
    End point title
    Number of Participants With Clinically Meaningful Changes in Vital Signs
    End point description
    Vital sign assessments included pulse rate, blood pressure (systolic and diastolic blood pressure) and body temperature. Number of participants with potential clinically meaningful changes in vital signs which were deemed clinically significant by the investigator were reported. The SAF included all enrolled participants 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: Participants
    12
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Total REGN3918

    Close Top of page
    End point title
    Serum Concentrations of Total REGN3918
    End point description
    Serum Concentrations of total REGN3918 was reported. The pharmacokinetic (PK) analysis set includes all participants who received any study drug and who had at least 1 non-missing result for concentration of REGN3918 following the first dose of study drug. Participants will be analyzed according to the treatment actually received. Here, “n= number analysed” signifies those participants who were evaluable at the specified categories.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Day 0), End of infusion at Days 0, 2, 7, 28, 56, 84, 112, 140, and 182
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: milligram/Liter (mg/L)
    arithmetic mean (standard deviation)
        At Day 0 (Pre-dose) (n=24)
    0 ( 0 )
        At Day 0 (End of Infusion) (n=24)
    605 ( 214 )
        At Day 2 (End of Infusion) (n-24)
    429 ( 159 )
        At Day 7 (End of Infusion) (n=24)
    292 ( 80.5 )
        At Day 28 (End of Infusion) (n=23)
    324 ( 97.5 )
        At Day 56 (End of Infusion) (n=22)
    368 ( 148 )
        At Day 84 (End of Infusion) (n=22)
    363 ( 152 )
        At Day 112 (End of Infusion) (n=23)
    379 ( 186 )
        At Day 140 (End of Infusion) (n=23)
    430 ( 225 )
        At Day 182 (End of infusion) (n=24)
    435 ( 221 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) Response to REGN3918

    Close Top of page
    End point title
    Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) Response to REGN3918
    End point description
    Number of participants with treatment-emergent ADA response to REGN3918 was reported. The ADA analysis set (AAS) included all participants who received any study drug and who had at least 1 non-missing ADA result from the REGN3918 ADA assay after the first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26
    End point values
    REGN3918
    Number of subjects analysed
    24
    Units: Participants
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose to Week 26
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    REGN3918
    Reporting group description
    Participants received a single loading dose of REGN3918 30 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1, followed by a maintenance regimen of 800 milligrams (mg) subcutaneous (SC) injection on Day 8 once weekly (QW) up to 26 weeks of treatment period.

    Serious adverse events
    REGN3918
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    REGN3918
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 24 (54.17%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 24 (37.50%)
         occurrences all number
    10
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    3 / 24 (12.50%)
         occurrences all number
    7
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 24 (12.50%)
         occurrences all number
    3
    Nausea
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 24 (12.50%)
         occurrences all number
    3
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jun 2019
    Protocol Amendment 2: Removed Sponsor as a responsible party in the confirmation of a breakthrough hemolysis event. Added language to clarify that blood collection should occur if a breakthrough hemolysis event is suspected. Updated the duration of the open-label extension study. Removed irrelevant information related to blinding for the interim analysis. This is an open-label study. Revised exclusion requirement for peripheral blood absolute neutrophil count to <500/μL. Revised description of PNH erythrocytes and granulocytes to reflect typical laboratory output for these analytes. Updated inclusion criterion #3 to specify PNH granulocytes that are denoted as polymorphonuclear (PMN).

    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
    For support, Contact us.
    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.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA