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

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.

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