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   43846   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:
    A Phase 2b, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose-Finding, Multi-Center Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects

    Summary
    EudraCT number
    		 2011-006020-20
    Trial protocol
    		 HU   CZ   PL   BG  
    Global end of trial date
    02 Dec 2013

    Results information
    Results version number
    		 v3(current)
    This version publication date
    18 Feb 2017
    First version publication date
    02 Jul 2015
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    015K-CL-RA22
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01565655
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development, Inc. (APGD)
    Sponsor organisation address
    1 Astellas Way, Northbrook, IL, United States, 60062
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc. (APGD), Astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development, Inc. (APGD), Astellas.resultsdisclosure@astellas.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
    02 Dec 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Dec 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Dec 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to evaluate the safety and efficacy of ASP015K in moderate to severe Rheumatoid Arthritis (RA) subjects.
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 This study was comprised of up to a 4-week screening period, a 12-week treatment period and a 30-day follow-up period. Once informed consent was obtained, the disease-modifying antirheumatic drug (DMARD) washout period (as applicable) could begin prior to screening. During screening (day -28 to day -1), entry criteria were confirmed and screening procedures were performed. Randomization occurred on day 1 and study drug was administered for 12 weeks (day 1 to day 84). At the end of treatment (EOT), end of study (EOS) procedures and a follow-up assessment of adverse events (AEs) were conducted for up to 30 days (day 85 to day 115). DMARD Washout Period: Period of time during which patients do not receive specific DMARD medications, and the effects of the DMARD medication are eliminated (or assumed to be eliminated). The DMARD washout period in this trial begins 1 to 26 weeks prior to start of study drug (duration is based on the disease-modifying antirheumatic drug used).
    Evidence for comparator
    		 Placebo was used as comparative drug. ASP015K matching placebo tablets contain the same ingredients as the test drug except for active drug substance and hydroxy-propyl cellulose.
    Actual start date of recruitment
    19 Jun 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 57
    Country: Number of subjects enrolled
    Bulgaria: 12
    Country: Number of subjects enrolled
    Czech Republic: 25
    Country: Number of subjects enrolled
    Hungary: 25
    Country: Number of subjects enrolled
    Mexico: 32
    Country: Number of subjects enrolled
    United States: 138
    Worldwide total number of subjects
    289
    EEA total number of subjects
    119
    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)
    249
    From 65 to 84 years
    40
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This multi-center study was conducted at 41 sites, 19 sites in the US, 3 sites in Bulgaria, 4 sites in the Czech Republic, 5 sites in Hungary, 6 sites in Poland and 4 sites in Mexico. The Principal Investigator at each site was a licensed clinician with experience in the therapeutic area of rheumatoid arthritis (RA).

    Pre-assignment
    Screening details
    		 The study was comprised of a screening period of up to 4 weeks (28 days), a treatment period of 12 weeks and a follow-up period of 30 days.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    This was a double-blind study. The investigator, patient, clinical staff and Sponsor’s study management team were blinded to treatment assignments.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 This arm consisted of matching ASP015K placebo taken orally with food, for 12 weeks (days 1-84) after randomization.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    ASP015K matching placebo tablets contained the same ingredients as the test drug except for active drug substance and hydroxy-propyl cellulose. Placebo was to be taken orally with food, daily for 12 weeks (days 1-84) after randomization. The first dose was taken on Baseline/Day 1 of the treatment period at the site.

    Arm title
    		 ASP015K 25 mg once daily
    Arm description
    		 This arm consisted of ASP015K 25 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP015K
    Investigational medicinal product code
    ASP015K
    Other name
    Peficitinib (USAN)
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The test drug for this study is ASP015K. ASP015K is a round, yellow, film-coated tablet. ASP015K 25 mg once daily was to be taken orally with food, daily for 12 weeks (days 1-84) after randomization.

    Arm title
    		 ASP015K 50 mg once daily
    Arm description
    		 This arm consisted of ASP015K 50 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP015K
    Investigational medicinal product code
    ASP015K
    Other name
    Peficitinib (USAN)
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The test drug for this study is ASP015K. ASP015K is a round, yellow, film-coated tablet. ASP015K 50 mg once daily was to be taken orally with food, daily for 12 weeks (days 1-84) after randomization.

    Arm title
    		 ASP015K 100 mg once daily
    Arm description
    		 This arm consisted of ASP015K 100 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP015K
    Investigational medicinal product code
    ASP015K
    Other name
    Peficitinib (USAN)
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The test drug for this study is ASP015K. ASP015K is a round, yellow, film-coated tablet. ASP015K 100 mg once daily was to be taken orally with food, daily for 12 weeks (days 1-84) after randomization.

    Arm title
    		 ASP015K 150 mg once daily
    Arm description
    		 This arm consisted of ASP015K 150 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP015K
    Investigational medicinal product code
    ASP015K
    Other name
    Peficitinib (USAN)
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The test drug for this study is ASP015K. ASP015K is a round, yellow, film-coated tablet. ASP015K 150 mg once daily was to be taken orally with food, daily for 12 weeks (days 1-84) after randomization.

    Number of subjects in period 1
    		Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Started
    51
    59
    57
    58
    64
    Completed
    49
    50
    49
    54
    60
    Not completed
    2
    9
    8
    4
    4
         Protocol violation
    -
    1
    1
    1
    -
         Adverse event
    1
    4
    2
    1
    2
         Patient non-compliant
    -
    -
    1
    -
    -
         Withdrawal by subject
    1
    1
    3
    2
    1
         Lack of efficacy
    -
    1
    1
    -
    1
         Treatment interrupted due to adverse event
    -
    1
    -
    -
    -
         Treatment interrupted due to antibiotic use
    -
    1
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 This arm consisted of matching ASP015K placebo taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 25 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 25 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 50 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 50 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 100 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 100 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 150 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 150 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group values
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily Total
    Number of subjects
    		 51 59 57 58 64 289
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Age values were based on the Safety Analysis Set (SAF) population. The SAF was defined as all patients who received at least 1 dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 52.7 ( 12.2 ) 52.6 ( 10.2 ) 54.8 ( 10 ) 54.9 ( 11.3 ) 54.4 ( 12.5 ) -
    Gender categorical
    Gender values are based on the SAF population.
    Units: Subjects
        Female
    		 42 46 48 51 50 237
        Male
    		 9 13 9 7 14 52

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 This arm consisted of matching ASP015K placebo taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 25 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 25 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 50 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 50 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 100 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 100 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Reporting group title
    ASP015K 150 mg once daily
    Reporting group description
    		 This arm consisted of ASP015K 150 mg once a daily taken orally with food, for 12 weeks (days 1-84) after randomization.

    Subject analysis set title
    H1 Metabolite - ASP015K 25 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the Pharmacokinetic Analysis Set (PKAS). The PKAS consisted of all patients who received at least 1 dose of study drug and who had values of drug concentration for at least 1 time point. The PKAS population included all of the patients treated with ASP015K that were also included in the Full Analysis Set (FAS - all randomized subjects that received at least one study drug dose) and Safety Analysis Set (SAF-all patients who received at least 1 dose of study drug).

    Subject analysis set title
    H1 Metabolite - ASP015K 50 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H1 Metabolite - ASP015K 100 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H1 Metabolite - ASP015K 150 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H2 Metabolite - ASP015K 25 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H2 Metabolite - ASP015K 50 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS. )

    Subject analysis set title
    H2 Metabolite - ASP015K 100 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H2 Metabolite - ASP015K 150 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H4 Metabolite - ASP015K 25 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H4 Metabolite - ASP015K 50 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H4 Metabolite - ASP015K 100 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Subject analysis set title
    H4 Metabolite - ASP015K 150 mg (PKAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The study analysis population consisted of the PKAS.

    Primary: Percentage of participants achieving a response in American College of Rheumatology (ACR) criteria for 20% improvement in disease severity (ACR 20) using the C-reactive protein (CRP) level (ACR20-CRP) at week 12

    		 Close Top of page
    End point title
    		 Percentage of participants achieving a response in American College of Rheumatology (ACR) criteria for 20% improvement in disease severity (ACR 20) using the C-reactive protein (CRP) level (ACR20-CRP) at week 12
    End point description
    The study analysis population consisted of the Full Analysis Set (FAS), defined as all randomized subjects that received at least one study drug dose. ACR20-CRP responder determined at week 12 if ACR response criteria was met: At least 20% reduction from baseline at week 12 TJC68 count, At least 20% reduction from baseline at week 12 SJC66 count, At least 20% reduction from baseline at week 12 in any 3 of 5 ACR components: subject’s global assessment of arthritis pain SGAP (100mm visual analog scale VAS; score 0=no pain, score 100=very severe pain), subject’s global assessment of arthritis SGA (100mm VAS; score 0=no disease activity, score 100mm=very severe disease activity), PGA (100mm VAS; score 0=no disease activity, score 100mm=very severe disease activity), Health Assessment Questionnaire-Disability Index HAQ-DI (score from 0 to 3, higher score=greater disability), CRP (mg/dL, higher values= >inflammation). Patient defined as a non-responder if the patient was not a responder.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Number of subjects analysed
    51 [1]
    59 [2]
    57 [3]
    58 [4]
    64 [5]
    Units: percentage of participants
    number (not applicable)
        Responder (R)
    29.4
    22
    36.8
    48.3
    56.3
        Non-Responder (NR)
    70.6
    78
    63.2
    51.7
    43.8
    Notes
    [1] - R (N= 15), NR (N= 36)
    [2] - R (N= 13), NR (N= 46)
    [3] - R (N= 21), NR (N= 36)
    [4] - R (N= 28), NR (N= 30)
    [5] - R (N= 36), NR (N= 28)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    LOCF: Last Observation Carried Forward for missing ACR20 components. NRI: Non-Responder Imputation for missing ACR response. ACR components were LOCFed first and then ACR20 response was calculated. In addition, all subjects with RA rescue therapy prior to or at Week 12 were classified as nonresponders. The total number of subjects in the statistical analysis are the responders in the Placebo group (15) and ASP015K 25 mg (13).
    Comparison groups
    Placebo v ASP015K 25 mg once daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005 [6]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 1.61
    Notes
    [6] - The odds ratio (OR > 1 favors ASP015K) and P value were based on a logistic regression model with effects for treatment group and geographic region.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    LOCF: Last Observation Carried Forward for missing ACR20 components. NRI: Non-Responder Imputation for missing ACR response. ACR components were LOCFed first and then ACR20 response was calculated. In addition, all subjects with RA rescue therapy prior to or at Week 12 were classified as nonresponders. The total number of subjects in the statistical analysis are the responders in the Placebo group (15) and ASP015K 50 mg (21).
    Comparison groups
    Placebo v ASP015K 50 mg once daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.805 [7]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 3.13
    Notes
    [7] - The odds ratio (OR > 1 favors ASP015K) and P value were based on a logistic regression model with effects for treatment group and geographic region.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    LOCF: Last Observation Carried Forward for missing ACR20 components. NRI: Non-Responder Imputation for missing ACR response. ACR components were LOCFed first and then ACR20 response was calculated. In addition, all subjects with RA rescue therapy prior to or at Week 12 were classified as nonresponders. The total number of subjects in the statistical analysis are the responders in the Placebo group (15) and ASP015K 100 mg (28).
    Comparison groups
    Placebo v ASP015K 100 mg once daily
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.054 [8]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 5.23
    Notes
    [8] - The odds ratio (OR > 1 favors ASP015K) and P value were based on a logistic regression model with effects for treatment group and geographic region.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    LOCF: Last Observation Carried Forward for missing ACR20 components. NRI: Non-Responder Imputation for missing ACR response. ACR components were LOCFed first and then ACR20 response was calculated. In addition, all subjects with RA rescue therapy prior to or at Week 12 were classified as nonresponders. The total number of subjects in the statistical analysis are the responders in the Placebo group (15) and ASP015K 150 mg (36).
    Comparison groups
    Placebo v ASP015K 150 mg once daily
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001 [9]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.44
         upper limit
    		 6.92
    Notes
    [9] - The odds ratio (OR > 1 favors ASP015K) and P value were based on a logistic regression model with effects for treatment group and geographic region.

    Primary: Trough plasma concentration of ASP015K and metabolites

    		 Close Top of page
    End point title
    		 Trough plasma concentration of ASP015K and metabolites [10] [11]
    End point description
    The study analysis population consisted of the Pharmacokinetic Analysis Set (PKAS). The PKAS consisted of all patients who received at least 1 dose of study drug and who had values of drug concentration for at least 1 time point.
    End point type
    Primary
    End point timeframe
    Up to week 12.
    Notes
    [10] - 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: This pharmacokinetic (PK) endpoint pertained to only those arms/subject analysis sets with ASP015K treatment since it measured the trough plasma concentration of ASP015K and metabolites. This was not applicable to the placebo treatment arm.
    [11] - 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: Descriptive statistics have been summarized for trough plasma concentrations of ASP015K, and metabolites by active treatment group and time point for each analyte.
    End point values
    		 ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily H1 Metabolite - ASP015K 25 mg (PKAS) H1 Metabolite - ASP015K 50 mg (PKAS) H1 Metabolite - ASP015K 100 mg (PKAS) H1 Metabolite - ASP015K 150 mg (PKAS) H2 Metabolite - ASP015K 25 mg (PKAS) H2 Metabolite - ASP015K 50 mg (PKAS) H2 Metabolite - ASP015K 100 mg (PKAS) H2 Metabolite - ASP015K 150 mg (PKAS) H4 Metabolite - ASP015K 25 mg (PKAS) H4 Metabolite - ASP015K 50 mg (PKAS) H4 Metabolite - ASP015K 100 mg (PKAS) H4 Metabolite - ASP015K 150 mg (PKAS)
    Number of subjects analysed
    59 [12]
    57 [13]
    58 [14]
    64 [15]
    59 [16]
    57 [17]
    58 [18]
    64 [19]
    59 [20]
    57 [21]
    58 [22]
    64 [23]
    59 [24]
    57 [25]
    58 [26]
    64 [27]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Baseline
    0.754 ( 5.6392 )
    3.004 ( 22.482 )
    6.485 ( 48.9613 )
    0.781 ( 5.3492 )
    0.039 ( 0.298 )
    0.036 ( 0.2673 )
    0.989 ( 7.4704 )
    0.099 ( 0.7862 )
    0.861 ( 6.5035 )
    5.674 ( 42.4611 )
    13.729 ( 103.6539 )
    0.309 ( 2.005 )
    0.116 ( 0.8729 )
    0.112 ( 0.8379 )
    0.57 ( 4.3061 )
    0.077 ( 0.4962 )
        Week 1
    0.881 ( 1.1244 )
    1.472 ( 1.1549 )
    3.023 ( 2.4352 )
    8.286 ( 26.5097 )
    2.072 ( 3.2626 )
    2.748 ( 1.9102 )
    7.471 ( 8.0531 )
    14.436 ( 26.3264 )
    2.408 ( 3.4033 )
    5.27 ( 8.5534 )
    10.613 ( 9.4295 )
    44.534 ( 176.3971 )
    1.114 ( 0.9671 )
    1.903 ( 1.4679 )
    3.463 ( 2.402 )
    8.409 ( 16.5609 )
        Week 2
    1.631 ( 5.9792 )
    1.373 ( 0.9128 )
    6.184 ( 21.8638 )
    14.356 ( 46.1079 )
    2.156 ( 4.0801 )
    2.789 ( 2.1451 )
    7.453 ( 10.1198 )
    12.642 ( 17.5732 )
    4.383 ( 15.9018 )
    5.436 ( 8.5164 )
    11.998 ( 16.0264 )
    36.376 ( 113.6776 )
    1.326 ( 2.1325 )
    1.783 ( 1.0238 )
    3.77 ( 3.5126 )
    7.043 ( 7.8633 )
        Week 4
    2.215 ( 5.7659 )
    1.745 ( 2.1049 )
    3.145 ( 4.4099 )
    10.174 ( 33.6779 )
    1.824 ( 2.3861 )
    3.069 ( 2.7708 )
    6.617 ( 10.5697 )
    13.6 ( 22.7147 )
    5.23 ( 16.3477 )
    5.952 ( 6.2121 )
    10.688 ( 15.8643 )
    43.166 ( 162.0641 )
    1.449 ( 2.0105 )
    2.16 ( 2.1099 )
    3.347 ( 3.7267 )
    9.317 ( 18.2902 )
        Week 8
    1.022 ( 2.0704 )
    1.842 ( 1.7768 )
    5.614 ( 15.026 )
    6.477 ( 6.2216 )
    1.475 ( 1.0352 )
    3.819 ( 4.0106 )
    7.738 ( 16.2141 )
    10.932 ( 21.8831 )
    2.448 ( 4.2744 )
    9.028 ( 19.397 )
    18.554 ( 47.2131 )
    35.541 ( 139.4458 )
    1.078 ( 1.2251 )
    2.707 ( 3.0481 )
    4.776 ( 10.8524 )
    7.027 ( 6.0709 )
        Week 12
    1.034 ( 1.5076 )
    2.172 ( 2.1518 )
    3.615 ( 3.8422 )
    5.964 ( 5.2095 )
    1.369 ( 1.3726 )
    4.363 ( 5.3775 )
    5.24 ( 5.7651 )
    11.484 ( 28.8065 )
    2.464 ( 3.7308 )
    8.372 ( 11.7188 )
    13.515 ( 22.8604 )
    20.289 ( 40.9056 )
    1.013 ( 1.0075 )
    3.318 ( 5.5703 )
    3.204 ( 2.689 )
    6.603 ( 5.95 )
    Notes
    [12] - [N= Baseline/57, Week 1/45, Week 2/46, Week 4/42, Week 8/41, Week 12/42]
    [13] - [N= Baseline/56, Week 1/45, Week 2/51, Week 4/45, Week 8/43, Week 12/44]
    [14] - [N= Baseline/57, Week 1/43, Week 2/47, Week 4/48, Week 8/46, Week 12/45]
    [15] - [N= Baseline/63, Week 1/49, Week 2/52, Week 4/48, Week 8/49, Week 12/44]
    [16] - [N= Baseline/57, Week 1/45, Week 2/46, Week 4/44, Week 8/42, Week 12/43]
    [17] - [N= Baseline/56, Week 1/45, Week 2/52, Week 4/43, Week 8/45, Week 12/43]
    [18] - [N= Baseline/57, Week 1/44, Week 2/47, Week 4/49, Week 8/45, Week 12/45]
    [19] - [N= Baseline/63, Week 1/48, Week 2/51, Week 4/48, Week 8/50, Week 12/44]
    [20] - [N= Baseline/57, Week 1/44, Week 2/46, Week 4/44, Week 8/41, Week 12/42]
    [21] - [N= Baseline/56, Week 1/45, Week 2/52, Week 4/44, Week 8/43, Week 12/41]
    [22] - [N= Baseline/57, Week 1/43, Week 2/47, Week 4/49, Week 8/45, Week 12/45]
    [23] - [N= Baseline/63, Week 1/48, Week 2/51, Week 4/47, Week 8/49, Week 12/44]
    [24] - [N= Baseline/57, Week 1/46, Week 2/46, Week 4/44, Week 8/41, Week 12/44]
    [25] - [N= Baseline/56, Week 1/45, Week 2/52, Week 4/44, Week 8/45, Week 12/44]
    [26] - [N= Baseline/57, Week 1/44, Week 2/47, Week 4/49, Week 8/46, Week 12/44]
    [27] - [N= Baseline/63, Week 1/49, Week 2/51, Week 4/48, Week 8/48, Week 12/44]
    No statistical analyses for this end point

    Secondary: Percentage of participants achieving American College of Rheumatology criteria for 50% improvement in disease severity using the c-reactive protein level (ACR50-CRP) response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of participants achieving American College of Rheumatology criteria for 50% improvement in disease severity using the c-reactive protein level (ACR50-CRP) response at Week 12
    End point description
    The study analysis population consisted of the FAS. ACR components were Last Observation Carried Forward (LOCF) first and then the response was calculated. In addition, all patients with RA rescue therapy prior to or at week 12 were classified as non-responders. ACR50-CRP responder is defined as per ACR20 but using 50% instead of 20%.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Number of subjects analysed
    51 [28]
    59 [29]
    57 [30]
    58 [31]
    64 [32]
    Units: percentage of participants
    number (not applicable)
        Responders (R)
    9.8
    15.3
    24.6
    27.6
    28.1
        Non-Responders (NR)
    90.2
    84.7
    75.4
    72.4
    71.9
    Notes
    [28] - R (N= 5), NR (N= 46)
    [29] - R (N= 9), NR (N= 50)
    [30] - R (N= 14), NR (n= 43)
    [31] - R (N= 16), NR (n= 42)
    [32] - R (N= 18), NR (n= 46)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (5) and ASP015K 25 mg (9).
    Comparison groups
    Placebo v ASP015K 25 mg once daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.272 [33]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 5.34
    Notes
    [33] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (5) and ASP015K 50 mg (14).
    Comparison groups
    Placebo v ASP015K 50 mg once daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.43 [34]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 9.03
    Notes
    [34] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (5) and ASP015K 100 mg (16).
    Comparison groups
    Placebo v ASP015K 100 mg once daily
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.074 [35]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.29
         upper limit
    		 11.76
    Notes
    [35] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (5) and ASP015K 150 mg (18).
    Comparison groups
    Placebo v ASP015K 150 mg once daily
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.076 [36]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 11.27
    Notes
    [36] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).

    Secondary: Percentage of participants achieving American College of Rheumatology criteria for 70% improvement in disease severity using the c-reactive protein level (ACR70-CRP) response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of participants achieving American College of Rheumatology criteria for 70% improvement in disease severity using the c-reactive protein level (ACR70-CRP) response at Week 12
    End point description
    The study analysis population consisted of the FAS. ACR components were Last Observation Carried Forward (LOCF) first and then the response was calculated. In addition, all patients with RA rescue therapy prior to or at week 12 were classified as non-responders. ACR70-CRP responder is defined as per ACR20 but using 70% instead of 20%.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Number of subjects analysed
    51 [37]
    59 [38]
    57 [39]
    58 [40]
    64 [41]
    Units: percentage of participants
    number (not applicable)
        Responders (R)
    7.8
    6.8
    15.8
    19
    10.9
        Non-Responders (NR)
    92.2
    93.2
    84.2
    81
    89.1
    Notes
    [37] - R (N= 4), NE (N= 47)
    [38] - R (N= 4), NE (N= 55)
    [39] - R (N= 9), NE (N= 48)
    [40] - R (N= 11), NE (N= 47)
    [41] - R (N= 7), NE (N= 57)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (4) and ASP015K 25 mg (4).
    Comparison groups
    Placebo v ASP015K 25 mg once daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.171 [42]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 3.52
    Notes
    [42] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (4) and ASP015K 50 mg (9).
    Comparison groups
    Placebo v ASP015K 50 mg once daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.334 [43]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 7.55
    Notes
    [43] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (4) and ASP015K 100 mg (11).
    Comparison groups
    Placebo v ASP015K 100 mg once daily
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.032 [44]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 10.76
    Notes
    [44] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    The total number of subjects in the statistical analysis are the responders in the Placebo group (4) and ASP015K 150 mg (7).
    Comparison groups
    Placebo v ASP015K 150 mg once daily
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.969 [45]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 5.54
    Notes
    [45] - The odds ratio (odds ratio > 1 favors ASP015K) and p-value were based on a logistic regression model with effects for treatment group and geographic region (North America, Europe, Latin America).

    Secondary: Change from Baseline/Day 1 to Week 12/Early Termination (ET) in Disease Activity Score in 28 Joints (DAS28) score based on the CRP level (DAS28-CRP) at week 12

    		 Close Top of page
    End point title
    		 Change from Baseline/Day 1 to Week 12/Early Termination (ET) in Disease Activity Score in 28 Joints (DAS28) score based on the CRP level (DAS28-CRP) at week 12
    End point description
    The study analysis population consisted of the FAS. DAS28-CRP is used to assess disease activity for RA. The DAS28-CRP score includes the TJC28 (refers to tender joint count based on 28 joints) and SJC28 (refers to swollen joint count based on 28 joints), the CRP level (measured in mg/dL was to be converted to mg/L for analysis purposes) and the subject's general health (SGA, measured on 100 mm Visual Analog Scale [VAS]. Higher DAS28-CRP scores indicate greater disease activity. Missing DAS28 component values were imputed using LOCF.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Number of subjects analysed
    51
    59
    57
    58
    64
    Units: units on a scale
        least squares mean (standard error)
    -1.16 ( 0.182 )
    -1.24 ( 0.169 )
    -1.52 ( 0.173 )
    -2.11 ( 0.176 )
    -2.01 ( 0.165 )
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Difference between Placebo vs. ASP015K 25 mg.
    Comparison groups
    Placebo v ASP015K 25 mg once daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.726 [46]
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares (LS) Mean of Difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.55
         upper limit
    		 0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.237
    Notes
    [46] - P-value was based on an ANCOVA model with fixed effects for treatment and geographic region, treatment-by-geographic region interaction term (if the interaction term is significant at 0.10 level) and baseline DAS28-CRP score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Difference between Placebo vs. ASP015K 50 mg.
    Comparison groups
    Placebo v ASP015K 50 mg once daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.131 [47]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean of Difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Notes
    [47] - P-value was based on an ANCOVA model with fixed effects for treatment and geographic region, treatment-by-geographic region interaction term (if the interaction term is significant at 0.10 level) and baseline DAS28-CRP score as a covariate.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Difference between Placebo vs. ASP015K 100 mg.
    Comparison groups
    Placebo v ASP015K 100 mg once daily
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001 [48]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean of Difference
    Point estimate
    -0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.42
         upper limit
    		 -0.47
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.239
    Notes
    [48] - P-value was based on an ANCOVA model with fixed effects for treatment and geographic region, treatment-by-geographic region interaction term (if the interaction term is significant at 0.10 level) and baseline DAS28-CRP score as a covariate.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Difference between Placebo vs. ASP015K 150 mg.
    Comparison groups
    Placebo v ASP015K 150 mg once daily
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001 [49]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean of Difference
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.31
         upper limit
    		 -0.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.233
    Notes
    [49] - P-value was based on an ANCOVA model with fixed effects for treatment and geographic region, treatment-by-geographic region interaction term (if the interaction term is significant at 0.10 level) and baseline DAS28-CRP score as a covariate.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    A treatment-emergent AE (TEAE) was defined as any AE that started or worsened in severity after initial dose of study drug through the follow-up period.
    Adverse event reporting additional description
    An adverse event was any untoward medical occurrence in a patient administered a study drug and which did not necessarily have a causal relationship with the treatment. Adverse events were based on the Safety Analysis Set (SAF) population. The SAF was defined as all patients who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Reporting group 1 description

    Reporting group title
    ASP015K 25 mg once daily
    Reporting group description
    		 Reporting group 2 description

    Reporting group title
    ASP015K 50 mg once daily
    Reporting group description
    		 Reporting group 3 description

    Reporting group title
    ASP015K 100 mg once daily
    Reporting group description
    		 Reporting group 4 description

    Reporting group title
    ASP015K 150 mg once daily
    Reporting group description
    		 Reporting group 5 description

    Serious adverse events
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 59 (3.39%)
    2 / 57 (3.51%)
    4 / 58 (6.90%)
    2 / 64 (3.13%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Investigations
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 64 (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
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    1 / 57 (1.75%)
    0 / 58 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 64 (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
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    2 / 58 (3.45%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    1 / 57 (1.75%)
    0 / 58 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    1 / 57 (1.75%)
    0 / 58 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 59 (1.69%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 64 (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
    Synovial cyst
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 59 (1.69%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 64 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo ASP015K 25 mg once daily ASP015K 50 mg once daily ASP015K 100 mg once daily ASP015K 150 mg once daily
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 51 (13.73%)
    10 / 59 (16.95%)
    5 / 57 (8.77%)
    17 / 58 (29.31%)
    16 / 64 (25.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 59 (1.69%)
    0 / 57 (0.00%)
    4 / 58 (6.90%)
    1 / 64 (1.56%)
         occurrences all number
    1
    1
    0
    5
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 51 (1.96%)
    4 / 59 (6.78%)
    1 / 57 (1.75%)
    4 / 58 (6.90%)
    0 / 64 (0.00%)
         occurrences all number
    1
    4
    1
    4
    0
    Nausea
         subjects affected / exposed
    0 / 51 (0.00%)
    2 / 59 (3.39%)
    1 / 57 (1.75%)
    3 / 58 (5.17%)
    6 / 64 (9.38%)
         occurrences all number
    0
    2
    1
    3
    6
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 59 (0.00%)
    3 / 57 (5.26%)
    0 / 58 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    1
    0
    4
    0
    2
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 51 (3.92%)
    4 / 59 (6.78%)
    0 / 57 (0.00%)
    4 / 58 (6.90%)
    5 / 64 (7.81%)
         occurrences all number
    2
    4
    0
    4
    5
    Urinary tract infection
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 59 (1.69%)
    0 / 57 (0.00%)
    2 / 58 (3.45%)
    5 / 64 (7.81%)
         occurrences all number
    3
    1
    0
    3
    5
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 59 (0.00%)
    1 / 57 (1.75%)
    3 / 58 (5.17%)
    1 / 64 (1.56%)
         occurrences all number
    0
    0
    1
    3
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Jan 2012
    The changes included in Amendment 4 are summarized below: ● Dosing instructions revised to state “take with food” ● Screening period and safety follow-up period extended to 4 weeks (28 days) and 30 days, respectively ● The follow-up period for subject not rolling-over into the extension study extended to 30 days ● Clarifications and other administrative changes made These changes to the protocol were included prior to the enrollment of any patients
    31 May 2012
    The changes included in Amendment 2 are summarized below: ● “Monotherapy” removed from trial design ● Allowed and prohibited concomitant medications updated ● Required washout periods for previous DMARDs updated ● Stratification by geographic region added ● Supine blood pressure requirement removed ● Estimated glomerular filtration rate (eGFR) calculation added ● Use of dosing diary added ● Clarifications and other administrative changes made These changes to the protocol were included prior to the enrollment of any patients.
    05 Dec 2012
    The changes included in Amendment 3 (Czech Republic-specific amendment) are summarized below: ● Age limitation to only enroll patients under the age of 65 years added ● Language regarding compliance with local practice and guidance for tuberculosis screening via purified protein derivative skin testing added These changes to the protocol were included prior to the enrollment of any patients in the Czech Republic.
    18 Dec 2012
    The changes included in Amendment 4 (Bulgaria-specific amendment) are summarized below: ● Eligible patient population as it relates to required prior RA treatment clarified These changes to the protocol were included prior to the enrollment of any patients in Bulgaria.
    01 Apr 2013
    The changes included in Amendment 5 are summarized below: ● Number of planned sites revised ● Optional messenger RNA expression profiling included ● Allowed and prohibited concomitant medications updated ● Inclusion criteria revised to require a demonstrated inadequate response or intolerance to prior DMARD treatment ● Inclusion criteria revised to add contraception requirements for both men and women ● Exclusion criteria revised to include other malabsorption syndromes. ● Significant (absolute lymphocyte count [ALC] < 750/mm3) or severe (ALC < 500/mm3) lymphopenia added as an exclusion and discontinuation criteria, respectively ● Recording of prior rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) testing results added ● Clarifications and other administrative changes made These changes to the protocol were included after the enrollment of approximately 97 patients, but did not affect the overall outcome of the study.
    05 Jun 2013
    The changes included in Amendment 6 (Czech Republic-specific amendment) are summarized below: ● Inclusion criteria revised to include age cap at < 65 years This change to the protocol was included after the enrollment of approximately 181 patients, but did not affect the overall outcome of the study.

    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-Fri Apr 19 12:36:22 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA