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   44339   clinical trials with a EudraCT protocol, of which   7369   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:
    A Phase 1/2, Randomized, Single-Blind, Placebo-Controlled, Single-Ascending and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Antiviral Efficacy Study of Subcutaneously Administered ALN-HBV in Healthy Adult Subjects and Non-cirrhotic Patients with Chronic Hepatitis B Virus (HBV) Infection

    Summary
    EudraCT number
    		 2015-004360-10
    Trial protocol
    		 GB  
    Global end of trial date
    06 Oct 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Oct 2018
    First version publication date
    20 Oct 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALN-HBV-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02826018
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alnylam Pharmaceuticals, Inc.
    Sponsor organisation address
    300 Third Street, Cambridge, MA, United States, 02142
    Public contact
    Investor Relations and Corporate Communications, Alnylam Pharmaceuticals, Inc., +1 866 330 0326, Investors@alnylam.com
    Scientific contact
    Chief Medical Officer, Alnylam Pharmaceuticals, Inc., +1 866 330 0326, medinfo@alnylam.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
    06 Oct 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Oct 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of single or multiple doses of ALN-HBV in healthy adult subjects and non-cirrhotic subjects with chronic hepatitis B virus (HBV) infection when administered as monotherapy or concomitantly with the anti-HBV nucleoside, entecavir, or the anti-HBV nucleotide, tenofovir.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Jun 2016
    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: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    24
    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)
    24
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 One clinical study site in the United Kingdom participated in this study.

    Pre-assignment
    Screening details
    		 Twenty four healthy subjects were enrolled in Part A of the study. The study was terminated before the enrollment of subjects into Parts B and C.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 A single dose of matching placebo was administered.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single dose of matching placebo (sterile normal saline: 0.9% sodium chloride [NaCl]) was administered subcutaneously (SC) on Day 1.

    Arm title
    		 ALN-HBV 0.1 mg/kg
    Arm description
    		 A single dose of 0.1 mg/kg ALN-HBV was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALN-HBV
    Investigational medicinal product code
    Other name
    ALN-66810
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single dose of ALN-HBV was administered SC on Day 1.

    Arm title
    		 ALN-HBV 0.3 mg/kg
    Arm description
    		 A single dose of 0.3 mg/kg ALN-HBV was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALN-HBV
    Investigational medicinal product code
    Other name
    ALN-66810
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single dose of ALN-HBV was administered SC on Day 1.

    Arm title
    		 ALN-HBV 1.0 mg/kg
    Arm description
    		 A single dose of 1.0 mg/kg ALN-HBV was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALN-HBV
    Investigational medicinal product code
    Other name
    ALN-66810
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single dose of ALN-HBV was administered SC on Day 1.

    Arm title
    		 ALN-HBV 3.0 mg/kg
    Arm description
    		 A single dose of 3.0 mg/kg ALN-HBV was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALN-HBV
    Investigational medicinal product code
    Other name
    ALN-66810
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single dose of ALN-HBV was administered SC on Day 1.

    Number of subjects in period 1
    		Placebo ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Started
    6
    3
    3
    6
    6
    Completed
    6
    3
    3
    6
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 A single dose of matching placebo was administered.

    Reporting group title
    ALN-HBV 0.1 mg/kg
    Reporting group description
    		 A single dose of 0.1 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 0.3 mg/kg
    Reporting group description
    		 A single dose of 0.3 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 1.0 mg/kg
    Reporting group description
    		 A single dose of 1.0 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 3.0 mg/kg
    Reporting group description
    		 A single dose of 3.0 mg/kg ALN-HBV was administered.

    Reporting group values
    		 Placebo ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg Total
    Number of subjects
    		 6 3 3 6 6 24
    Age categorical
    Units: Subjects
    Age continuous
    Safety Analysis Set included all subjects, who received any amount of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 26.8 ( 5.49 ) 30.7 ( 4.04 ) 24.3 ( 6.66 ) 24.8 ( 7.17 ) 20.5 ( 0.84 ) -
    Gender categorical
    Safety Analysis Set included all subjects, who received any amount of study drug.
    Units: Subjects
        Female
    		 2 1 2 4 1 10
        Male
    		 4 2 1 2 5 14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 A single dose of matching placebo was administered.

    Reporting group title
    ALN-HBV 0.1 mg/kg
    Reporting group description
    		 A single dose of 0.1 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 0.3 mg/kg
    Reporting group description
    		 A single dose of 0.3 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 1.0 mg/kg
    Reporting group description
    		 A single dose of 1.0 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 3.0 mg/kg
    Reporting group description
    		 A single dose of 3.0 mg/kg ALN-HBV was administered.

    Primary: Percentage of Subjects With Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Adverse Events (AEs) [1]
    End point description
    An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety Analysis Set: All subjects, who received any amount of study drug.
    End point type
    Primary
    End point timeframe
    Part A: Up to Day 29; additional laboratory tests were obtained after Day 29 at the discretion of the Investigator (or designee), incorporating input from the Sponsor and/or Safety Review committee (SRC) up to Day 151.
    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: Only summary statistics were planned to be reported for this endpoint.
    End point values
    		 Placebo ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    6
    3
    3
    6
    6
    Units: percentage of subjects
        number (not applicable)
    33.3
    66.7
    33.3
    50.0
    100
    No statistical analyses for this end point

    Secondary: Maximum Concentration (Cmax) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Maximum Concentration (Cmax) of ALN-HBV in Plasma [2]
    End point description
    Pharmacokinetic (PK) Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoint for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    3
    3
    6
    6
    Units: nanogram (ng)/ milllilitre (mL)
        arithmetic mean (standard deviation)
    27.9 ( 4.20 )
    64.7 ( 23.7 )
    215 ( 44.6 )
    856 ( 197 )
    No statistical analyses for this end point

    Secondary: Time to Cmax (tmax) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Time to Cmax (tmax) of ALN-HBV in Plasma [3]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    3
    3
    6
    6
    Units: hour (hr)
        median (full range (min-max))
    2.00 (2.00 to 2.00)
    4.05 (2.02 to 6.00)
    4.05 (2.00 to 4.07)
    4.05 (2.00 to 8.03)
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time 0 to Time of Last Measurable Concentration (AUClast) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Area Under the Concentration-Time Curve from Time 0 to Time of Last Measurable Concentration (AUClast) of ALN-HBV in Plasma [4]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    3
    3
    6
    6
    Units: hr* microgram (ug)/mL
        arithmetic mean (standard deviation)
    0.162 ( 0.0438 )
    0.473 ( 0.149 )
    1.92 ( 0.395 )
    8.85 ( 1.35 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time 0 to Time 24 Hour (AUC0-24) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Area Under the Concentration-Time Curve from Time 0 to Time 24 Hour (AUC0-24) of ALN-HBV in Plasma [5]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [6]
    1 [7]
    5 [8]
    6 [9]
    Units: hr*ug/mL
        arithmetic mean (standard deviation)
    ( )
    0.742 ( 99999 )
    2.26 ( 0.416 )
    8.85 ( 1.35 )
    Notes
    [6] - No evaluable data were collected for this endpoint.
    [7] - Subjects analysed is the number of subjects analysed for this endpoint.
    [8] - Subjects analysed is the number of subjects analysed for this endpoint.
    [9] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) of ALN-HBV in Plasma [10]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [11]
    1 [12]
    5 [13]
    5 [14]
    Units: hr*ug/mL
        arithmetic mean (standard deviation)
    ( )
    0.756 ( 99999 )
    2.32 ( 0.428 )
    9.16 ( 1.36 )
    Notes
    [11] - No evaluable data were collected for this endpoint.
    [12] - Subjects analysed is the number of subjects analysed for this endpoint.
    [13] - Subjects analysed is the number of subjects analysed for this endpoint.
    [14] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Half-life (t1/2) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Half-life (t1/2) of ALN-HBV in Plasma [15]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [16]
    1 [17]
    5 [18]
    5 [19]
    Units: hr
        arithmetic mean (standard deviation)
    ( )
    3.92 ( 99999 )
    4.14 ( 0.693 )
    4.81 ( 1.40 )
    Notes
    [16] - No evaluable data were collected for this endpoint.
    [17] - Subjects analysed is the number of subjects analysed for this endpoint.
    [18] - Subjects analysed is the number of subjects analysed for this endpoint.
    [19] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL/F) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Apparent Clearance (CL/F) of ALN-HBV in Plasma [20]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [21]
    1 [22]
    5 [23]
    5 [24]
    Units: Litre/hr
        arithmetic mean (standard deviation)
    ( )
    24.8 ( 99999 )
    27.9 ( 4.94 )
    20.9 ( 3.81 )
    Notes
    [21] - No evaluable data were collected for this endpoint.
    [22] - Subjects analysed is the number of subjects analysed for this endpoint.
    [23] - Subjects analysed is the number of subjects analysed for this endpoint.
    [24] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/F) of ALN-HBV in Plasma

    		 Close Top of page
    End point title
    		 Apparent Volume of Distribution (Vz/F) of ALN-HBV in Plasma [25]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 and 48 hours, and Day 8
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [26]
    1 [27]
    5 [28]
    5 [29]
    Units: litre(s)
        arithmetic mean (standard deviation)
    ( )
    140 ( 99999 )
    166 ( 40.5 )
    149 ( 70.9 )
    Notes
    [26] - No evaluable data were collected for this endpoint.
    [27] - Subjects analysed is the number of subjects analysed for this endpoint.
    [28] - Subjects analysed is the number of subjects analysed for this endpoint.
    [29] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Fraction Excreted from Time 0 to Time 24 Hour (Fe0-24) of ALN-HBV in Urine

    		 Close Top of page
    End point title
    		 Fraction Excreted from Time 0 to Time 24 Hour (Fe0-24) of ALN-HBV in Urine [30]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, >6 hours, >12 hours, >24 hours
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    3
    3
    6
    6
    Units: percent
        arithmetic mean (standard deviation)
    12.0 ( 1.88 )
    7.95 ( 5.90 )
    10.3 ( 7.09 )
    17.3 ( 5.90 )
    No statistical analyses for this end point

    Secondary: Renal Clearance (CLr) of ALN-HBV

    		 Close Top of page
    End point title
    		 Renal Clearance (CLr) of ALN-HBV [31]
    End point description
    PK Analysis Set: All subjects who received any amount of study drug, had at least one post-dose blood sample for study drug measurement, and had sufficient data to calculate at least 1 PK parameter for ALN-HBV.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, >6 hours, >12 hours, >24 hours, Day 3, Day 8
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The placebo arm was not included in endpoints for pharmacokinetics.
    End point values
    		 ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Number of subjects analysed
    0 [32]
    1 [33]
    5 [34]
    6
    Units: Litre/hr
        arithmetic mean (standard deviation)
    ( )
    3.72 ( 99999 )
    4.05 ( 0.802 )
    3.77 ( 1.02 )
    Notes
    [32] - No evaluable data were collected for this endpoint.
    [33] - Subjects analysed is the number of subjects analysed for this endpoint.
    [34] - Subjects analysed is the number of subjects analysed for this endpoint.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 29; additional laboratory tests were obtained after Day 29 at the discretion of the Investigator (or designee), incorporating input from the Sponsor and/or Safety Review committee (SRC) up to Day 151.
    Adverse event reporting additional description
    Safety Analysis Set: All subjects, who received any amount of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 A single dose of matching placebo was administered.

    Reporting group title
    ALN-HBV 0.1 mg/kg
    Reporting group description
    		 A single dose of 0.1 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 0.3 mg/kg
    Reporting group description
    		 A single dose of 0.3 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 1.0 mg/kg
    Reporting group description
    		 A single dose of 1.0 mg/kg ALN-HBV was administered.

    Reporting group title
    ALN-HBV 3.0 mg/kg
    Reporting group description
    		 A single dose of 3.0 mg/kg ALN-HBV was administered.

    Serious adverse events
    		 Placebo ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo ALN-HBV 0.1 mg/kg ALN-HBV 0.3 mg/kg ALN-HBV 1.0 mg/kg ALN-HBV 3.0 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    6 / 6 (100.00%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    5
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Medical device site reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Genital herpes
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Mar 2016
    Removed Part D multiple dosing in subjects who are anti-HBV treatment-naïve, clarified that the maximum possible dose in Part C is 3.0 mg/kg, amended the stopping rules for Part C to state that dosing will be discontinued if >/=1 subject experiences a serious adverse event (SAE) considered to be possibly or definitely related to study drug, and clarified reasons leading to dosing discontinuation.
    26 Jan 2017
    Included specific alanine transaminase (ALT) inclusion criteria and increased liver function test monitoring. Also, each subsequent dose escalation after 0.1 mg/kg ALN-HBV was to be preceded by protocol-specified Safety Review Committee (SRC) review of safety data. The following additional protocol changes were made: • For Parts B and C, a normal and stable serum ALT was added as a specific inclusion criterion. • For Part B, an additional time point for laboratory assessment was added to Day 22. • Alcohol use during the duration of the study was updated in Exclusion Criteria for Parts A, B, and C. Additionally, clarified that the use of herbal supplements was prohibited during the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    06 Oct 2017
    The study was terminated as part of a business decision to advance a new HBV development candidate and not due to any safety concerns. At the time of study termination all healthy volunteers had completed Part A, and postdosing safety monitoring was considered complete per the SRC.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Only Part A of the study was completed. No subjects were enrolled in Parts B and C, which were to include subjects with HBV infection. Therefore, the efficacy endpoint of hepatitis B surface antigen (HBsAg) levels could not be assessed.
    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-Thu May 29 14:21:18 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA