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    Clinical Trial Results:
    A Randomised, Double-blind, Multicentre Phase III Study to Assess the Efficacy and Safety of RGB-14-P Compared to Prolia® in Women with Postmenopausal Osteoporosis

    Summary
    EudraCT number
    		 2020-006017-38
    Trial protocol
    		 PL   CZ   HU   BG   ES   IT  
    Global end of trial date
    15 Nov 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Oct 2024
    First version publication date
    25 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RGB-14-101
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05087030
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND: 146025
    Sponsors
    Sponsor organisation name
    Gedeon Richter Plc.
    Sponsor organisation address
    1103 Budapest, Gyömrői út 19-21, Budapest, Hungary,
    Public contact
    Medical Information Service, Gedeon Richter Plc., medinfo@richter.hu
    Scientific contact
    Medical Information Service, Gedeon Richter Plc., medinfo@richter.hu
    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
    13 Feb 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Nov 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Efficacy To demonstrate similar efficacy and effect of RGB 14 P with US licensed Prolia® on BMD at the lumbar spine at Week 52 in female subjects with postmenopausal osteoporosis Pharmacodynamics To demonstrate similar pharmacodynamics (AUEC of %CfB in sCTX) of RGB 14 P with US licensed Prolia® in female subjects with postmenopausal osteoporosis (only required for EMA)
    Protection of trial subjects
    This study was conducted in accordance with the principles laid down in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidance – ICH E6(R2), and in accordance with the Declaration of Helsinki and in accordance with applicable national laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Sep 2021
    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
    Poland: 225
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    Bulgaria: 67
    Country: Number of subjects enrolled
    Czechia: 61
    Country: Number of subjects enrolled
    Hungary: 39
    Country: Number of subjects enrolled
    Italy: 23
    Country: Number of subjects enrolled
    United States: 20
    Country: Number of subjects enrolled
    Ukraine: 3
    Worldwide total number of subjects
    473
    EEA total number of subjects
    450
    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)
    186
    From 65 to 84 years
    287
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted between 21-September-2021 (first subject first visit) to 15-November-2023 (last subject last visit).

    Pre-assignment
    Screening details
    		 Subjects who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.

    Period 1
    Period 1 title
    Main period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 RGB-14-P
    Arm description
    		 Subjects received RGB-14-P as subcutaneous (SC) injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).
    Arm type
    		 Experimental

    Investigational medicinal product name
    RGB-14-P
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    RGB-14-P was provided as a single-dose (1 mL solution) pre-filled syringe for subcutaneous injection administration.

    Arm title
    		 Prolia®
    Arm description
    		 Subjects received Prolia® as SC injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prolia®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Prolia® was provided as a single-dose (1 mL solution) pre-filled syringe for subcutaneous injection administration.

    Number of subjects in period 1
    		RGB-14-P Prolia®
    Started
    242
    231
    Completed
    225
    211
    Not completed
    17
    20
         Exclusion criteria met
    1
    -
         Adverse event, serious fatal
    -
    1
         Consent withdrawn by subject
    8
    13
         Adverse event, non-fatal
    2
    2
         Unspecified
    1
    2
         Lost to follow-up
    3
    -
         Study objective confounded
    1
    -
         Subject's personal reason
    -
    2
         Protocol deviation
    1
    -
    Period 2
    Period 2 title
    Transition period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 RGB-14-P to RGB-14-P
    Arm description
    		 Subjects who received RGB-14-P during the main period were re-randomized and received Prolia® as SC injection on day 1 of treatment period 3 (week 52).
    Arm type
    		 Experimental

    Investigational medicinal product name
    RGB-14-P
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    RGB-14-P was provided as a single-dose (1 mL solution) pre-filled syringe for subcutaneous injection administration.

    Arm title
    		 Prolia® to RGB-14-P
    Arm description
    		 Subjects who received Prolia® during the main period were re-randomized and received RGB-14-P as SC injection on Day 1 of treatment period 3 (week 52).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prolia®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Prolia® was provided as a single-dose (1 mL solution) pre-filled syringe for subcutaneous injection administration.

    Arm title
    		 Prolia® to Prolia®
    Arm description
    		 Subjects who received Prolia® during the main period were re-randomized and received Prolia® as SC injection on Day 1 of treatment period 3 (week 52).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prolia®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Prolia® was provided as a single-dose (1 mL solution) pre-filled syringe for subcutaneous injection administration.

    Number of subjects in period 2 [1]
    		RGB-14-P to RGB-14-P Prolia® to RGB-14-P Prolia® to Prolia®
    Started
    63
    62
    63
    Completed
    63
    62
    62
    Not completed
    0
    0
    1
         Consent withdrawn by subject
    -
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only a subset of patients continued the study in the Transition period (as outlined in the clinical study protocol).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    RGB-14-P
    Reporting group description
    		 Subjects received RGB-14-P as subcutaneous (SC) injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).

    Reporting group title
    Prolia®
    Reporting group description
    		 Subjects received Prolia® as SC injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).

    Reporting group values
    		 RGB-14-P Prolia® Total
    Number of subjects
    		 242 231 473
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 100 86 186
        From 65-84 years
    		 142 145 287
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.7 ( 5.20 ) 66.8 ( 4.91 ) -
    Gender categorical
    Units: Subjects
        Female
    		 242 231 473
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    RGB-14-P
    Reporting group description
    		 Subjects received RGB-14-P as subcutaneous (SC) injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).

    Reporting group title
    Prolia®
    Reporting group description
    		 Subjects received Prolia® as SC injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).
    Reporting group title
    RGB-14-P to RGB-14-P
    Reporting group description
    		 Subjects who received RGB-14-P during the main period were re-randomized and received Prolia® as SC injection on day 1 of treatment period 3 (week 52).

    Reporting group title
    Prolia® to RGB-14-P
    Reporting group description
    		 Subjects who received Prolia® during the main period were re-randomized and received RGB-14-P as SC injection on Day 1 of treatment period 3 (week 52).

    Reporting group title
    Prolia® to Prolia®
    Reporting group description
    		 Subjects who received Prolia® during the main period were re-randomized and received Prolia® as SC injection on Day 1 of treatment period 3 (week 52).

    Primary: Percentage Change from Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)

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    End point title
    		 Percentage Change from Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)
    End point description
    Percentage change from baseline in lumbar bone BMD was assessed. BMD at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). This outcome measure was assessed for main period. The Full analysis set (FAS) included all subjects to whom the investigational medicinal product (IMP) has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure.
    End point type
    Primary
    End point timeframe
    Week 52
    End point values
    		 RGB-14-P Prolia®
    Number of subjects analysed
    222
    206
    Units: percent
        arithmetic mean (standard deviation)
    5.68 ( 3.535 )
    5.19 ( 4.118 )
    Statistical analysis title
    		 RGB-14-P v/s Prolia®
    Statistical analysis description
    The analysis was performed with an ANCOVA model with %CfB in lumbar spine BMD at Week 52 as the dependent variable; covariates were treatment Arm (RGB-14-P and US licenced Prolia), stratification factors at randomization (Previous use of bisphosphonates [yes/no] and geographical region [Europe, US], Baseline BMD value in lumbar spine, machine type and machine type*baseline BMD value interaction.
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    428
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.402
         upper limit
    		 1.09
    Notes
    [1] - Comparison between Study Treatment Groups

    Primary: Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in serum Type I Collagen C-telopeptide (sCTX)

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    End point title
    		 Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in serum Type I Collagen C-telopeptide (sCTX)
    End point description
    The AUEC of %CfB in sCTX of RGB-14-P was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female subjects was demonstrated with postmenopausal osteoporosis. This outcome measure was assessed for main period only. The pharmacodynamic analysis set (PDS) included all subjects in the safety population with at least one evaluable pharmacodynamic (PD) parameter (%CfB and AUEC) and not had any protocol deviations that have a relevant impact on sCTX or serum procollagen type 1 N-terminal propeptide (P1NP) results included in the pharmacodynamic parameter calculation. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure.
    End point type
    Primary
    End point timeframe
    Week 26
    End point values
    		 RGB-14-P Prolia®
    Number of subjects analysed
    241
    229
    Units: milligram(s)/deciliter(dL)*day
        geometric mean (confidence interval 95%)
    13501.300 (12737.814 to 14264.794)
    13344.650 (12583.291 to 14106.002)
    Statistical analysis title
    		 RGB-14-P v/s Prolia®
    Statistical analysis description
    The analysis was performed with a mixed-effects model ANCOVA on natural log-transformed AUEC data as the dependent variable and the following model covariates: Treatment Arm, Stratification factors (Previous use of bisphosphonates [yes/no] and Geographical region [Europe, US], Log of baseline sCTX.
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    470
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [2]
    Method
    Parameter type
    		 Geometric Mean Ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.978
         upper limit
    		 1.046
    Notes
    [2] - Comparison between Study Treatment Groups

    Secondary: Percentage Change from Baseline (%CfB) in Total Hip BMD

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    End point title
    		 Percentage Change from Baseline (%CfB) in Total Hip BMD
    End point description
    Percentage Change from Baseline in total hip BMD was assessed. The FAS included all subjects to whom the IMP has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    225
    63
    211
    62
    63
    Units: percent
    arithmetic mean (standard deviation)
        Week 26 (n = 225, 62, 211, 58, 62)
    2.42 ( 2.659 )
    2.46 ( 2.712 )
    2.69 ( 2.519 )
    2.81 ( 2.607 )
    3.35 ( 2.559 )
        Week 52 (n = 220, 63, 205, 60, 63)
    3.42 ( 2.916 )
    3.03 ( 3.103 )
    3.49 ( 2.872 )
    3.36 ( 2.696 )
    4.21 ( 3.452 )
        Week 78 (n = 0, 62, 0, 62, 60)
    9999 ( 9999 )
    4.24 ( 3.381 )
    9999 ( 9999 )
    4.12 ( 3.128 )
    4.95 ( 3.849 )
    Statistical analysis title
    		 RGB-14-P v/s Prolia® at Week 26
    Statistical analysis description
    at Week 26
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.792
         upper limit
    		 0.165
    Notes
    [3] - Mixed Model Repeated Measures
    Statistical analysis title
    		 RGB-14-P v/s Prolia® at Week 52
    Statistical analysis description
    at Week 52
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.68
         upper limit
    		 0.358
    Notes
    [4] - Mixed model repeated measures

    Secondary: Percentage Change from Baseline (%CfB) in Lumbar Spine BMD

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    End point title
    		 Percentage Change from Baseline (%CfB) in Lumbar Spine BMD
    End point description
    Percentage Change from Baseline in lumbar spine BMD was assessed. The Full analysis set (FAS) included all subjects to whom the IMP has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 26 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    227
    63
    218
    62
    63
    Units: percent
    arithmetic mean (standard deviation)
        Week 26 (n= 227, 62, 218, 61, 63)
    3.56 ( 3.747 )
    3.98 ( 3.185 )
    3.45 ( 4.227 )
    3.39 ( 3.848 )
    3.68 ( 4.979 )
        Week 78 (n= 0, 63, 0, 62, 60)
    9999 ( 9999 )
    7.03 ( 3.828 )
    9999 ( 9999 )
    7.06 ( 4.327 )
    7.09 ( 4.240 )
    Statistical analysis title
    		 RGB-14-P v/s Prolia® at Week 26
    Statistical analysis description
    Week 26
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    445
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.703
         upper limit
    		 0.769
    Notes
    [5] - mixed model for repeated measures

    Secondary: Percentage Change from Baseline (%CfB) in Femoral Neck BMD

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    End point title
    		 Percentage Change from Baseline (%CfB) in Femoral Neck BMD
    End point description
    Percentage Change from Baseline in femoral neck BMD was assessed by DXA. The FAS included all subjects to whom the IMP has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    225
    63
    211
    62
    63
    Units: percent
    arithmetic mean (standard deviation)
        Week 26 (n= 225, 62, 211, 58, 62)
    1.88 ( 3.040 )
    1.60 ( 2.833 )
    1.94 ( 3.610 )
    2.21 ( 3.296 )
    2.35 ( 4.057 )
        Week 52 (n= 220, 63, 205, 60, 63)
    2.42 ( 3.687 )
    1.95 ( 3.621 )
    2.64 ( 3.751 )
    2.60 ( 3.127 )
    3.24 ( 4.549 )
        Week 78 (n= 0, 63, 0, 62, 60)
    9999 ( 9999 )
    3.08 ( 4.259 )
    9999 ( 9999 )
    3.06 ( 3.337 )
    4.04 ( 4.764 )
    Statistical analysis title
    		 RGB-14-P v/s Prolia® at Week 26
    Statistical analysis description
    The analysis was performed with a mixed model repeated measures with observed %CfB in femoral neck BMD as the dependent variable; covariates were treatment arm (RGB-14-P and US licenced Prolia), stratification factors at randomization (Previous use of bisphosphonates [yes/no] and geographical region [Europe, US], Baseline BMD value in femoral neck, machine type and machine type*baseline BMD value interaction, study week and study week*treatment arm interaction.
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.727
         upper limit
    		 0.478
    Notes
    [6] - Mixed model repeated measures
    Statistical analysis title
    		 RGB-14-P v/s Prolia® at Week 52
    Statistical analysis description
    The analysis was performed with a mixed model repeated measures with observed %CfB in femoral neck BMD as the dependent variable; covariates were treatment arm (RGB-14-P and US licenced Prolia), stratification factors at randomization (Previous use of bisphosphonates [yes/no] and geographical region [Europe, US], Baseline BMD value in femoral neck, machine type and machine type*baseline BMD value interaction, study week and study week*treatment arm interaction.
    Comparison groups
    RGB-14-P v Prolia®
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.006
         upper limit
    		 0.359
    Notes
    [7] - Mixed model repeated measures

    Secondary: Number of Subjects with Vertebral Fragility Fracture

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    End point title
    		 Number of Subjects with Vertebral Fragility Fracture
    End point description
    Number of subjects with vertebral fragility fracture were assessed. Information on vertebral fractures was centrally collected through the evaluation of lateral thoraco-lumbar spine X-ray. The Full analysis set (FAS) included all subjects to whom the IMP has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    242
    63
    231
    62
    63
    Units: Subjects
        Week 52 (n= 242, 0, 231, 0, 0)
    4
    9999
    8
    9999
    9999
        Week 78 (n= 0, 63, 0, 62, 63)
    9999
    3
    9999
    4
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects with Non-Vertebral Fragility Fracture

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    End point title
    		 Number of Subjects with Non-Vertebral Fragility Fracture
    End point description
    Number of subjects with non-vertebral fragility fracture were assessed. Information on non-vertebral fractures was centrally collected through the evaluation of lateral thoraco-lumbar spine X-ray. The FAS included all subjects to whom the IMP has been randomized. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    242
    63
    231
    62
    63
    Units: Subjects
        Week 52 (n= 242, 0, 231, 0, 0)
    4
    9999
    10
    9999
    9999
        Week 78 (n= 0, 63, 0, 62, 63)
    9999
    2
    9999
    5
    3
    No statistical analyses for this end point

    Secondary: Percentage Change from Baseline (%CfB) in Serum Procollagen Type 1 N Terminal Propeptide (P1NP)

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    End point title
    		 Percentage Change from Baseline (%CfB) in Serum Procollagen Type 1 N Terminal Propeptide (P1NP)
    End point description
    Percentage Change from Baseline in serum P1NP was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female subjects with postmenopausal osteoporosis. The PDS included all subjects in safety population with at least one evaluable PD parameter (%CfB and AUEC) and not had any protocol deviations that have a relevant impact on sCTX or serum P1NP results included in PD parameter calculation. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 26, 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    234
    60
    220
    60
    62
    Units: percent
    arithmetic mean (standard deviation)
        Week 4 (n= 234, 60, 220, 59, 62)
    22.10 ( 14.905 )
    19.85 ( 13.939 )
    20.22 ( 15.091 )
    18.45 ( 15.835 )
    17.31 ( 15.524 )
        Week 26 (n= 216, 57, 211, 59, 60)
    65.92 ( 17.828 )
    68.42 ( 11.693 )
    62.89 ( 29.294 )
    63.41 ( 42.677 )
    66.08 ( 16.098 )
        Week 52 (n= 204, 60, 198, 60, 61)
    65.04 ( 19.131 )
    64.86 ( 16.902 )
    63.82 ( 21.712 )
    66.05 ( 20.428 )
    65.89 ( 17.651 )
        Week 78 (n= 0, 54, 0, 59, 58)
    9999 ( 9999 )
    64.12 ( 18.845 )
    9999 ( 9999 )
    66.91 ( 16.816 )
    63.08 ( 21.364 )
    No statistical analyses for this end point

    Secondary: Percentage Change from Baseline (%CfB) in serum Type I Collagen C-telopeptide (sCTX)

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    End point title
    		 Percentage Change from Baseline (%CfB) in serum Type I Collagen C-telopeptide (sCTX)
    End point description
    Percentage Change from Baseline in sCTX was assessed as part of pharmacodynamics parameter with US-licensed Prolia® was assessed in female subjects with postmenopausal osteoporosis. PDS included all subjects in safety population with at least one evaluable PD parameter (%CfB and AUEC) and not had any protocol deviations that have a relevant impact on sCTX or serum P1NP results included in PD parameter calculation. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 26, 52 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    234
    60
    220
    60
    62
    Units: percent
    arithmetic mean (standard deviation)
        Week 4 (n= 234, 60, 220, 59, 62)
    85.87 ( 9.567 )
    84.96 ( 11.206 )
    85.38 ( 15.501 )
    84.71 ( 23.071 )
    88.08 ( 5.832 )
        Week 26 (n= 216, 57, 211, 59, 60)
    69.74 ( 23.212 )
    67.29 ( 23.572 )
    61.51 ( 83.764 )
    53.23 ( 147.679 )
    71.27 ( 17.483 )
        Week 52 (n= 204, 60, 198, 60, 61)
    62.90 ( 28.995 )
    60.41 ( 31.958 )
    58.26 ( 63.927 )
    53.89 ( 94.853 )
    66.79 ( 24.151 )
        Week 78 (n= 0, 54, 0, 59, 59)
    9999 ( 9999 )
    58.70 ( 34.117 )
    9999 ( 9999 )
    53.32 ( 42.855 )
    57.38 ( 30.562 )
    No statistical analyses for this end point

    Secondary: Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    The safety and tolerability of RGB-14-P with US-licensed Prolia® in female subjects with postmenopausal osteoporosis was assessed. Safety analysis set (SAF) included all subjects who received at least one full or partial dose of IMP. Here, disc = discontinuation, IMP = Investigational Medicinal Product, s/ws = severe or worse severity
    End point type
    Secondary
    End point timeframe
    Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    242
    63
    231
    62
    63
    Units: Subjects
        Any AE
    161
    0
    158
    0
    0
        Any TEAEs
    158
    30
    152
    25
    25
        Any TEAEs s/ws
    8
    0
    9
    1
    0
        Any treatment related TEAE
    36
    2
    32
    5
    1
        Any treatment related TEAE s/ws
    1
    0
    0
    0
    0
        Any serious TEAEs
    7
    0
    16
    0
    0
        Any serious TEAEs s/ws
    5
    0
    9
    0
    0
        Any non-serious TEAEs
    158
    30
    149
    25
    25
        Any AEs leading to subject disc
    2
    0
    3
    0
    0
        Any TEAEs leading to subject disc
    2
    0
    3
    0
    0
        Any treatment related TEAE leading to subject disc
    1
    0
    0
    0
    0
        Any TEAEs leading to disc of IMP
    2
    0
    2
    0
    0
        Any treatment related TEAE leading to disc of IMP
    1
    0
    0
    0
    0
        Any fracture TEAE
    9
    4
    18
    3
    1
        Any fracture TEAE s/ws
    2
    0
    1
    0
    0
        Any serious fracture TEAEs
    1
    0
    1
    0
    0
        Any serious fracture TEAEs s/ws
    1
    0
    1
    0
    0
        Deaths
    0
    0
    1
    0
    0
        Any AE leading to death
    0
    0
    1
    0
    0
        Any TEAE leading to death
    0
    0
    1
    0
    0
        Any injection site reactions
    0
    0
    2
    3
    1
        Any treatment related serious TEAE
    0
    0
    0
    0
    0
        Any treatment related serious TEAE s/ws
    0
    0
    0
    0
    0
        Any treatment related fracture TEAE
    0
    0
    0
    0
    0
        Any treatment related fracture TEAE s/ws
    0
    0
    0
    0
    0
        Any treatment related serious fracture TEAE
    0
    0
    0
    0
    0
        Any treatment related serious fracture TEAE s/ws
    0
    0
    0
    0
    0
        Any treatment related fatal serious TEAEs
    0
    0
    0
    0
    0
        Any injection site reactions of CTCAE grade ≥3
    0
    0
    0
    0
    0
        Any injection site reactions s/ws
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Anti-Drug Antibodies (ADAs)

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    End point title
    		 Number of Subjects with Anti-Drug Antibodies (ADAs)
    End point description
    Number of subjects with positive ADAs were assessed. Immunogenicity analysis set (IAS) included all subjects in the safety population who had the pre-dose immunogenicity result and at least one available postbaseline immunogenicity assessment. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that data was not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    239
    63
    228
    62
    62
    Units: Subjects
        Week 0 (n= 239, 63, 228, 62, 62)
    0
    0
    1
    0
    0
        Week 2 (n= 236, 63, 224, 60, 61)
    2
    0
    0
    0
    0
        Week 4 (n= 237, 63, 226, 60, 62)
    0
    0
    0
    0
    0
        Week 26 (n= 227, 63, 219, 62, 62)
    0
    0
    0
    0
    0
        Week 28 (n= 218, 60, 206, 58, 59)
    0
    0
    1
    0
    1
        Week 30 (n= 220, 63, 215, 62, 62)
    0
    0
    1
    0
    1
        Week 52 (n= 225, 63, 208, 62, 61)
    0
    0
    0
    0
    0
        Week 54 (n= 0, 62, 0, 61, 62)
    9999
    0
    9999
    0
    1
        Week 56 (n= 0, 63, 0, 62, 61)
    9999
    0
    9999
    0
    1
        Week 78 (n= 0, 63, 0, 62, 61)
    9999
    0
    9999
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Neutralizing Antibodies

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    End point title
    		 Number of Subjects with Neutralizing Antibodies
    End point description
    Number of subjects with positive neutralizing antibodies were assessed. IAS included all subjects in the safety population who had the pre-dose immunogenicity result and at least one available postbaseline immunogenicity assessment. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for this outcome measure. Here, 9999 indicates that the data were not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    2
    0 [8]
    2
    0 [9]
    1
    Units: Subjects
        Week 0 (n= 0, 0, 1, 0, 0)
    9999
    9999
    9999
        Week 2 (n= 2, 0, 0, 0, 0)
    1
    9999
    9999
        Week 4 (n= 0, 0, 0, 0, 0)
    9999
    9999
    9999
        Week 26 (n= 0, 0, 0, 0, 0)
    9999
    9999
    9999
        Week 28 (n= 0, 0, 1, 0, 1)
    9999
    1
    1
        Week 30 (n= 0, 0, 1, 0, 1)
    9999
    9999
    9999
        Week 52 (n= 0, 0, 0, 0, 0)
    9999
    9999
    9999
        Week 54 (n= 0, 0, 0, 0, 1)
    9999
    9999
    1
        Week 56 (n= 0, 0, 0, 0, 1)
    9999
    9999
    1
        Week 78 (n= 0, 0, 0, 0, 0)
    9999
    9999
    9999
    Notes
    [8] - Number of subjects analyzed were 0 due to no positive ADA response.
    [9] - Number of subjects analyzed were 0 due to no positive ADA response.
    No statistical analyses for this end point

    Secondary: Titre of ADAs

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    End point title
    		 Titre of ADAs
    End point description
    The immunogenicity of RGB -14- P with US-licensed Prolia® in female subjects with postmenopausal osteoporosis was assessed. IAS included all subjects in the safety population who had the pre-dose immunogenicity result and at least one available postbaseline immunogenicity assessment. Here, 'number of subjects analyzed' specifies all subjects who were evaluated for ADA. The outcome measure in this table is the titer, N refers to all subjects analyzed for ADA. (Only 7 samples, from 4 subjects were evaluated for titer). Here, '99999' indicates that titer was not evaluable due to no positive ADA response and '9999' indicates that data was not available due to insufficient number of subjects.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
    End point values
    		 RGB-14-P RGB-14-P to RGB-14-P Prolia® Prolia® to RGB-14-P Prolia® to Prolia®
    Number of subjects analysed
    239
    63
    228
    62
    62
    Units: titre
    median (full range (min-max))
        Week 0 (n= 239, 63, 228, 62, 62)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    302.0 (302 to 302)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 2 (n= 236, 63, 224, 60, 61)
    761.0 (60 to 1462)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 4 (n= 237, 63, 226, 60, 62)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 26 (n= 227, 63, 219, 62, 62)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 28 (n= 218, 60, 206, 58, 59)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    172.0 (172 to 172)
    99999 (99999 to 99999)
    172.0 (172 to 172)
        Week 30 (n= 220, 63, 215, 62, 62)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    211.0 (211 to 211)
    99999 (99999 to 99999)
    211.0 (211 to 211)
        Week 52 (n= 225, 63, 208, 62, 61)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Week 54 (n= 0, 62, 0, 61, 62)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    224.0 (224 to 224)
        Week 56 (n= 0, 63, 0, 62, 61)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    152.0 (152 to 152)
        Week 78 (n= 0, 63, 0, 62, 61)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78
    Adverse event reporting additional description
    Safety analysis set included all subjects who received at least one full or partial dose of IMP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    RGB-14-P
    Reporting group description
    		 Subjects received RGB-14-P as subcutaneous (SC) injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).

    Reporting group title
    Prolia®
    Reporting group description
    		 Subjects received Prolia® as SC injection on Day 1 of treatment period 1 (week 0) and treatment period 2 (week 26).

    Reporting group title
    RGB-14-P to RGB-14-P
    Reporting group description
    		 Subjects who received RGB-14-P during the main period were re-randomized and received Prolia® as SC injection on day 1 of treatment period 3 (week 52).

    Reporting group title
    Prolia® to RGB-14-P
    Reporting group description
    		 Subjects who received Prolia® during the main period were re-randomized and received RGB-14-P as SC injection on Day 1 of treatment period 3 (week 52).

    Reporting group title
    Prolia® to Prolia®
    Reporting group description
    		 Subjects who received Prolia® during the main period were re-randomized and received Prolia® as SC injection on Day 1 of treatment period 3 (week 52).

    Serious adverse events
    		 RGB-14-P Prolia® RGB-14-P to RGB-14-P Prolia® to RGB-14-P Prolia® to Prolia®
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 242 (2.89%)
    16 / 231 (6.93%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Follicular lymphoma
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 242 (0.41%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Lumbosacral radiculopathy
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Chronic gastritis
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial disorder
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 242 (0.41%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 242 (0.00%)
    1 / 231 (0.43%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 242 (0.41%)
    0 / 231 (0.00%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 RGB-14-P Prolia® RGB-14-P to RGB-14-P Prolia® to RGB-14-P Prolia® to Prolia®
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    100 / 242 (41.32%)
    85 / 231 (36.80%)
    4 / 63 (6.35%)
    3 / 62 (4.84%)
    6 / 63 (9.52%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    8 / 242 (3.31%)
    13 / 231 (5.63%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    9
    14
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    14 / 242 (5.79%)
    4 / 231 (1.73%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    15
    5
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 242 (4.96%)
    10 / 231 (4.33%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    16
    13
    0
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    25 / 242 (10.33%)
    24 / 231 (10.39%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    25
    25
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    23 / 242 (9.50%)
    21 / 231 (9.09%)
    1 / 63 (1.59%)
    2 / 62 (3.23%)
    4 / 63 (6.35%)
         occurrences all number
    29
    28
    1
    2
    4
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 242 (9.50%)
    11 / 231 (4.76%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    34
    13
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    11 / 242 (4.55%)
    11 / 231 (4.76%)
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    13
    17
    0
    0
    0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    22 / 242 (9.09%)
    22 / 231 (9.52%)
    3 / 63 (4.76%)
    1 / 62 (1.61%)
    2 / 63 (3.17%)
         occurrences all number
    31
    27
    3
    1
    2

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Aug 2021
    The protocol was amended to Substantial Amendment 1, dated 03 Aug 2021, to incorporate and implement responses and suggestions made by the USFDA.
    10 Jan 2022
    The protocol was amended to Substantial Amendment 2, dated 10 Jan 2022, to incorporate and implement changes for statistical analysis, consistency with supporting study documents and suggestions made based on Investigator experiences.
    19 Jan 2023
    The protocol was amended to Substantial Amendment 3, dated 19 Jan 2023, to incorporate and implement 10% increase in the number of subjects to be enrolled for the Transition Period to meet the requirements of USFDA, considering the drop-out was higher than expected.

    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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    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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