Safety, Tolerability And Mechanism Of Action Of Boswellic Acids (BA) In Multiple Sclerosis (SABA)

Study Overview
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Brief Summary
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To determine the safety and tolerability of BOSWELAN in subjects with multiple sclerosis or clinically isolated syndrome and to describe the effect of Boswellic acids on the disease activity as assessed by monthly MRI measures.

Detailed Description
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Boswellic acids (BAs), the main biologically active compound of frankincense, are orally available and known to exhibit anti-inflammatory activities. This is a Phase IIa bicentric baseline-to-treatment study with the standardized frankincense extract Boswelan to test the safety, tolerability and efficacy of BAs in RR-MS patients. Following a 3-month screening phase, patients received an individualized dose finding identifying the highest well tolerated BOSWELAN dose for each patient. The primary outcome in the treatment phase (Stage 3) will first compare mean Gd-enhancing lesion number occurring during the 4 month baseline to mean Gd-enhancing lesion number occurring months 5, 6, 7, 8 on treatment in patients treated with a dose of at least 800 mg t.i.d.

Official Title
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Safety, Tolerability And Mechanism Of Action Of Boswellic Acids In Multiple Sclerosis and Clinically Isolated Syndrome: A MRI-Controlled, Multicenter, Baseline-To-Treatment, 32-Weeks, Open-Label, Phase IIa Trial

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Boswellic acids (BOSWELAN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18 and 65 years, inclusive* Females and Males (as no specific gender-related differences are expected, no specific gender distribution is planned. See GCP-V § 7 (2) Nr. 12) Subjects with a clinically isolated syndrome (high risk of conversion to MS) as well as subjects with clinically definite relapsing-remitting according to published criteria (50) Diseases with similar clinical neurological symptoms (e.g. lues, borreliosis, collagenosis or vasculitis) have been excluded by differential diagnostics EDSS score between 0.0 and 5.5, inclusive. Baseline MRI Lesion frequency of 0.5 or greater Patients are clinically stable, i.e. without relapse and not having received steroids within 30 days prior to inclusion Patients have either failed standard treatment (interferon beta, glatiramer acetate) by clinical measures or were not eligible for any of the standard treatments available or opted not to start or to continue with any of these treatments Exclusion Criteria: ALT (SGPT) or AST (SGOT) > three times the upper limit of normal Total white blood cell count < 3,000/mm3 Platelet count < 85,000/mm3 Creatinine > 1.5 mg/dl Serology indicating active hepatitis B or C infection or other chronic liver disease Positive pregnancy test, or breast-feeding female Nausea/vomiting as a frequent complaint History or signs of immunodeficiency Concurrent, clinically significant (as determined by the investigator) cardiac, immunological, pulmonary, neurological, renal, and/or other major disease If prior treatment was received, the subject must have been off treatment for the required period prior to enrollment (see Table 2). Table 2: Restrictions on pre-treatments Agent Glatiramer acetate (CopaxoneTM), Interferon beta (BetaferonTM, AvonexTM, RebifTM) IV Ig, Azathioprine (ImurekTM), Methotrexate, Cyclophosphamide (CytoxanTM), Mitoxantrone, plasma exchange, Cyclosporine, oral myelin, Cladribine, natalizumab, and other immunosuppressive treatments Corticosteroids, ACTH Time required off agent prior to enrollment 12 weeks 24 weeks 8 weeks Prior treatment with any other investigational drug or procedure for MS will be evaluated individually by the investigators. History of alcohol or drug abuse within the 5 years prior to enrollment Female subjects who are not post-menopausal or surgically sterile who are not using an highly effective method of birth control. Highly effective is defined as having a failure rate of <1%. Written documentation that the subject is post- menopausal or surgically sterile must be available prior to study start Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's returning for follow-up visits on schedule Previous participation in this study Participation in other pharmaceutical trials during this study or 3 months before Patients hospitalized due to juridical or legal regulation Known hypersensitivity to BA Known contraindications for MRI examinations including hypersensitivity to gadolinium, severe renal insufficiency, a mechanical heart valve or any kind of metallic implants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boswellic acids (BOSWELAN)<br>Baseline to treatment single arm - 4 months baseline and 8 months of treatment at a t.i.d. (Ter In Die (Latin: Three Times A Day) dose of between 400-1600 mg of BOSWELAN. | Drug: Boswellic acids (BOSWELAN)<br>* 8 months of treatment at a t.i.d. (Ter In Die (Latin: Three Times A Day) dose of between 400-1600 mg Boswelan<br>* Other names: BOSWELAN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of total Gd-enhancing lesions | Mean number of Gd-enhencing lesions comparing a baseline/pre-treatment interval of 3 months to a 3 months interval on treatment | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new active lesions (new Gd-enhancing lesions +new or enlarging non-enhancing T2 lesions) |  | 8 months | 
| Relapse rate | Annualized Relapse rate - comparing baseline to treatment | 8 months |