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   43845   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:
    SAFETY, TOLERABILITY AND MECHANISM OF ACTION OF BOSWELLIC ACIDS (BA) IN MULTIPLE SCLEROSIS (MS) AND CLINICALLY ISOLATED SYNDROME (CIS): A MRI-CONTROLLED, MULTICENTER, BASELINE-TO-TREATMENT, 32-WEEKS, OPEN-LABEL, PHASE IIA TRIAL IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS OR CLINICALLY ISOLATED SYNDROME

    Summary
    EudraCT number
    		 2009-014724-32
    Trial protocol
    		 DE  
    Global end of trial date
    07 Mar 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Oct 2022
    First version publication date
    25 Oct 2022
    Other versions
    Summary report(s)
    		 SABA_Synopsis results 2018_01_20

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SABA
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01450124
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University Medical Center Hamburg-Eppendorf (UKE)
    Sponsor organisation address
    Martinistrasse 52, Hamburg, Germany,
    Public contact
    MS Outpatient Unit, Institute for Neuroimmunology and Clinical Multiple Sclerosis (MS) Research, UKE, +49 40741054076, multiplesklerose@uke.uni-hamburg.de
    Scientific contact
    MS Outpatient Unit, Institute for Neuroimmunology and Clinical Multiple Sclerosis (MS) Research, UKE, +49 40741054076, multiplesklerose@uke.uni-hamburg.de
    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
    24 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Mar 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the safety and tolerability of a standardized frankincense extract ("Boswelan") in subjects with multiple sclerosis or clinically isolated syndrome
    Protection of trial subjects
    Patients were regularly and frequently monitored by clinical visits, laboratory parameters and magnetic resonance imaging. An independent data-safety monitoring board of three international Multiple Sclerosis experts followed all adverse events up during the trial. The study protocol and the trial was conducted by treating and examining all patients in accordance with the national (German) applicable laws, the international guidelines on good clinical practice (ICH-GCP), and the declaration of Helsinki. Further details are given in the study protocol (available via klarissa.stuerner@uksh.de).
    Background therapy
    		 best medical care
    Evidence for comparator
    		 in-vitro data inhibiting TH17 polarization in Multiple Sclerosis patients in cell culture
    Actual start date of recruitment
    01 Sep 2011
    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
    Germany: 38
    Worldwide total number of subjects
    38
    EEA total number of subjects
    38
    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)
    38
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Multiple Sclerosis patients between 18 and 55 years were recruited at the UK Hamburg Eppendorf, Department of neurology or at the NeuroCure Research Center at the Charité Berlin. Of 80 screened patients 38 patients were enrolled to the trial. Further details can be found at: https://jnnp.bmj.com/content/89/4/330

    Pre-assignment
    Screening details
    		 Subjects with clinically isolated syndrome (CIS) or clinically definite relapsing remitting multiple sclerosis (RRMS) fulfilling MRI inclusion criteria who either failed standard treatment by clinical measures or were not eligible for any of the standard treatments were given the opportunity to participate in the trial.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Single Arm
    Arm description
    		 We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-totreatment pilot study with an oral SFE in patients with RRMS. After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    standardised frankincence extract (SFE)
    Investigational medicinal product code
    Other name
    SFE
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    The SFE was provided as capsules containing 400 mg. After a 3-month baseline observation phase (stage 1) the patient participated in an individualised dose-finding phase (stage 2) during the first 8 weeks. Stage 2 was divided into two parts. In part 1, up to 400 mg capsules of an SFE were used to titrate up to a maximum well-tolerated dose or to a maximum of 4800 mg/day (whichever occurrd first), that is, 1600 mg three times a day in the first 28 days by adding one capsule every second or third day. After the individual maximum well-tolerated dose had been determined, the patients continued with that dose for another 28 days (part 2) for stabilisation and to assess tolerability. This was followed by 6 months of continuous treatment at this dose (stage 3). A minimum tolerated dose of 2400 mg/day was mandatory to continue with the trial. If a relapse occurred during the study, the patients were offered the option to discontinue the trial and revert to standard treatment.

    Number of subjects in period 1
    		Single Arm
    Started
    38
    completed month 8
    28
    Completed
    28
    Not completed
    10
         Consent withdrawn by subject
    3
         Physician decision
    4
         non-compliance to protocol
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Single Arm
    Reporting group description
    		 We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-totreatment pilot study with an oral SFE in patients with RRMS. After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.

    Reporting group values
    		 Single Arm Total
    Number of subjects
    		 38 38
    Age categorical
    Eligible patients were male or female between the ages of 18 and 55.
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 38 38
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
        Not recorded
    		 0 0
    Age continuous
    Units: years
        median (standard deviation)
    		 37.2 ± 10.0 -
    Gender categorical
    Units: Subjects
        Female
    		 29 29
        Male
    		 9 9
        Not recorded
    		 0 0
    EDSS AT BASELINE
    Expanded Disability Status Scale
    Units: Subjects
        EDSS score
    		 38 38
    Subject analysis sets

    Subject analysis set title
    Baseline (months -3 to 0)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Baseline (months -3 to 0)

    Subject analysis set title
    Treatment (months 5-8)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Treatment (months 5-8)

    Subject analysis sets values
    		 Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects
    28
    28
    Age categorical
    Eligible patients were male or female between the ages of 18 and 55.
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    28
    28
        From 65-84 years
    0
    0
        85 years and over
    0
    0
        Not recorded
    0
    0
    Age continuous
    Units: years
        median (standard deviation)
    38.0 ± 10.5
    38.0 ± 10.5
    Gender categorical
    Units: Subjects
        Female
        Male
        Not recorded
    EDSS AT BASELINE
    Expanded Disability Status Scale
    Units: Subjects
        EDSS score

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Single Arm
    Reporting group description
    		 We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-totreatment pilot study with an oral SFE in patients with RRMS. After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.

    Subject analysis set title
    Baseline (months -3 to 0)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Baseline (months -3 to 0)

    Subject analysis set title
    Treatment (months 5-8)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Treatment (months 5-8)

    Primary: Number of total Gadolinium-enhancing lesions

    		 Close Top of page
    End point title
    		 Number of total Gadolinium-enhancing lesions
    End point description
    End point type
    Primary
    End point timeframe
    Baseline (Months -3 to 0) versus Treatment (months 5 to 8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [1]
    28
    28
    Units: number
        median (inter-quartile range (Q1-Q3))
    -0.625 (-1.25 to -0.50)
    1.00 (0.75 to 3.38)
    0.50 (0.00 to 1.13)
    Notes
    [1] - per-protocol cohort (n=28)
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Baseline (months -3 to 0) v Treatment (months 5-8)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Confidence interval

    Primary: Volume of total enhancing lesions (new and persisting)

    		 Close Top of page
    End point title
    		 Volume of total enhancing lesions (new and persisting)
    End point description
    End point type
    Primary
    End point timeframe
    baseline (months -3 to 0) versus treatment (months 5-8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [2]
    28
    28
    Units: mm^3
        median (inter-quartile range (Q1-Q3))
    -829.0 (-2188 to -184)
    1753.5 (553.0 to 4974.5)
    185.00 (0.00 to 1450.00)
    Notes
    [2] - per-protocol cohort
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Baseline (months -3 to 0) v Treatment (months 5-8)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 = 0.0481
    Method
    		 t-test, 2-sided
    Confidence interval

    Primary: Volume of new enhancing lesions

    		 Close Top of page
    End point title
    		 Volume of new enhancing lesions
    End point description
    End point type
    Primary
    End point timeframe
    baseline (months -3 to 0) versus treatment (months 5 to 8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [3]
    28
    28
    Units: mm^3
        median (inter-quartile range (Q1-Q3))
    -611.0 (-1094 to -92)
    1087.00 (407.50 to 3343.00)
    92.50 (0.00 to 725.00)
    Notes
    [3] - per-protocol cohort
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Treatment (months 5-8) v Baseline (months -3 to 0)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 = 0.0243
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Number of new Gadolinium-enhancing lesions

    		 Close Top of page
    End point title
    		 Number of new Gadolinium-enhancing lesions
    End point description
    Number of new or enlarging gadolinium-enhancing lesions in cerebral MRI
    End point type
    Secondary
    End point timeframe
    Baseline (Months -3 to 0) versus Treatment (months 5 to 8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [4]
    28
    28
    Units: number
        median (inter-quartile range (Q1-Q3))
    -0.625 (-1.25 to -0.50)
    0.88 (0.63 to 2.63)
    0.25 (0.00 to 0.75)
    Notes
    [4] - per-protocol cohort
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Baseline (months -3 to 0) v Treatment (months 5-8)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Number of new T2 lesions

    		 Close Top of page
    End point title
    		 Number of new T2 lesions
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline (Months -3 to 0) versus Treatment (months 5 to 8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [5]
    28
    28
    Units: number
        median (inter-quartile range (Q1-Q3))
    -6.50 (-10.25 to -4.00)
    7.50 (4.88 to 12.88)
    0.25 (0.00 to 0.75)
    Notes
    [5] - per-protocol cohort
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Baseline (months -3 to 0) v Treatment (months 5-8)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: Change in volume of T2 lesions

    		 Close Top of page
    End point title
    		 Change in volume of T2 lesions
    End point description
    End point type
    Secondary
    End point timeframe
    baseline (months -3 to 0) versus treatment ( months 5 to 8)
    End point values
    		 Single Arm Baseline (months -3 to 0) Treatment (months 5-8)
    Number of subjects analysed
    28 [6]
    28
    28
    Units: mm^3
        median (inter-quartile range (Q1-Q3))
    -34.5 (-582 to 435)
    264.50 (-1048.50 to 1304.00)
    301.50 (-123.50 to 1045.00)
    Notes
    [6] - per-protocol cohort
    Statistical analysis title
    		 MRI outcomes PP
    Comparison groups
    Single Arm v Baseline (months -3 to 0) v Treatment (months 5-8)
    Number of subjects included in analysis
    84
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 = 0.9118
    Method
    		 t-test, 2-sided
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline till end of trial for each patient
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17
    Reporting groups
    Reporting group title
    SFE treated patients
    Reporting group description
    		 all patients included in the trial who participated in the treatment phase (even if only for hours or days); so anyone who has been exposed is reported here.

    Serious adverse events
    		 SFE treated patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 38 (10.53%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Broken ankle
    Additional description: Broken ankle after accidental fall after 27 months of SFE intake
         subjects affected / exposed
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tibia fracture
    Additional description: Tibia fracture during sports
         subjects affected / exposed
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Lupus vasculitis
    Additional description: Newly diagnosed Lupus erythematodes after 25 months of SFE intake
         subjects affected / exposed
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Anal fissure
    Additional description: need for emergency proctological procedure after diarrhea (infectios, had been acquired abroad in Asia)
         subjects affected / exposed
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 SFE treated patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 38 (89.47%)
    Gastrointestinal disorders
    diarrhea, gastric pain, stomache ache
         subjects affected / exposed
    32 / 38 (84.21%)
         occurrences all number
    32
    Infections and infestations
    common cold
         subjects affected / exposed
    26 / 38 (68.42%)
         occurrences all number
    26

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Apr 2015
    substancial amendment and new patient information (due to information about 2 cases of rheumatic disease in the trial and further information on estragole)

    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.
    no placebo cohort; this was only a pilot trial using a baseline-to-treatment design

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29248894
    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 01:06:27 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA