Pilot Study for Evaluation of Glatiramer Acetate in RRMS Patients With Comorbid Autoimmune Conditions
Multiple Sclerosis (MS) is an auto-immune neurodegenerative disease that affects more than
400,000 individuals in the United States, and 2.5 million worldwide
(www.nationalmssociety.org). The main pathogenic mechanism in MS involves an inflammatory
condition that damages the myelin of the central nervous system (CNS), resulting in axonal
damage and neurological impairment, often leading to severe disability. MS is one of the
most common causes of neurological disability in young and middle-aged adult individuals,
and as such has a tremendous physical, psychological and social impact on patients' lives.
MS is a complex disease diagnosed by McDonald criteria with different clinical and
pathological phenotypes. Several forms of MS have been described: Relapsing-Remitting
(RRMS), Secondary-Progressive MS (SPMS), Progressive-Relapsing MS (PRMS), and
Primary-Progressive MS (PPMS).
Glatiramer Acetate (GA) and Beta-Interferons (β-IFNs) are well established first-line
immunomodulating treatment options for relapsing remitting multiple sclerosis (RRMS) with
excellent safety profiles. The mechanisms of action of GA and IFNs are different. It is well
known that in general Disease-Modifying Treatments (DMTs) reduce relapse rate in more than
half of the multiple sclerosis (MS) patients who receive DMT, while having little if any
effect on the rest. It has been speculated that the response to beta-interferons or GA may
have genetic basis. As Axtell RC et al. indicated the experimental autoimmune
encephalomyeilits (EAE) in mouse caused by TH1 cells generally respond well to
interferon-beta, while EAE caused by TH17 cells get worse with interferon-beta.
Autoimmune disease is an extreme situation where the autoimmune response overshoots and goes
out of control. The other extreme is a degenerative disorder, where the autoimmune response
is not strong enough for effective protection, and degeneration therefore continues. GA
being an immunomodulator may provide both properly regulated immune suppression (in the case
of autoimmune disease) and properly regulated immune activation (in the case of the
Autoimmune conditions cluster in families with high risk for multiple sclerosis than in
general population which suggests that the disease might arise on a background of a
generalized susceptibility to autoimmunity. Occurrence of psoriasis, autoimmune thyroiditis,
vasculitis, rheumatoid arthritis, scleroderma, lupus are seen more commonly in MS patients.
Many of these patients initially get started on beta-IFNs, and usually do not do well on
them. According to Investigator's and the USC MS Comprehensive Care Center experience,
autoimmune co-morbidity associated with MS can serve as a biological marker predicting good
response to GA and unfavorable response to the IFNs.
A Non-randomized, Exploratory, Study to Assess Clinical Response to Gilenya® (Fingolimod) in a Cohort of Relapsing Remitting Hispanic MS Forms
The primary objective of this study is to determine the success of Gilenya® (fingolimod)
treatment in patients with MS of Hispanic descent relative to their ancestral background.
Therapeutic success will be determined by annualized relapse rate (ARR; defined as the
number of relapses divided by the person years followed) after initiation of treatment with
Gilenya® (fingolimod)in comparison to the relapse rate in the previous 12 months. This will
be determined based on medical chart extraction, in-person assessment and regular clinical
A secondary objective of this study is to investigate whether the efficacy of Gilenya®
(fingolimod) is superior or equal in HW which have higher loads of Amerindian versus
Caucasian background with opticospinal MS (OSMS-NMO neg) versus classical MS (CMS) in the
first 12 months using radiological and clinical parameters. The following measures will be
1. Number of relapse-free patients over the investigational period
2. Site of relapse defined as brain or spinal cord.
3. Sustained Disability progression will be defined as a one point (1) increase from
baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5)
increase in patients with baseline EDSS score of 5-5.5 or above after 3 months.
4. MRI changes as described as number of new T2 lesions and number of Gd-enhancing lesions
after 12 months from baseline.
Unknown status | Multiple Sclerosis | Not Multisite
Multi-center, Randomized, Double-blinded Assessment of Tecfidera® in Extending the Time to a First Attack in Radiologically Isolated Syndrome (RIS) (ARISE)
This is a multi-center, randomized, double-blinded study in which approximately 210 RIS
(radiologically isolated syndrome) subjects will be treated with either Tecfidera or placebo
for 2 years (1:1 randomization). Study participants, along with the treating and examining
physicians, will be blinded to treatment assignment. Central Clinical and Imaging Units will
screen all potential study subjects for inclusion/exclusion criteria. We expect to enroll all
RIS subjects within the U.S.
Following informed consent and verification of entry criteria by the core units, study
participants will be randomized 1:1 to either Tecfidera (120mg by mouth twice daily for 7
days with dose escalation to 240mg by mouth twice daily) or placebo. Clinical follow-up by
the treating physician will occur at weeks 0, 48, 96, 144 and/or End of Study and during or
immediately following clinical exacerbations. During clinical visits, comprehensive medical
history data will be obtained by the treating physician. All reported acute or progressive
clinical events will be adjudicated by the Central Clinical Unit. Clinical visits due to
suspected exacerbations associated with CNS (central nervous system) demyelination, and
associated diagnostic studies and treatments, will be covered under the medical standard of
care by third party payers. A recommendation to re-evaluate the patient within 3 months
following the clinical event to assess for extent of recovery will be made. In addition to
the face-to-face visits described above, study participants will be contacted over the
telephone at weeks 4, 8, 36, 60, 84, 108, and 132 to assess for medical or treatment
difficulties and for study medication compliance. Standardized MRI studies of the brain will
be performed at weeks 0, 96, 144 or End of Study. Clinical imaging studies of the brain
and/or spinal cord performed during or immediately following the onset of a clinical
exacerbation will be performed at the discretion of the site PI with scan costs covered under
the medical standard of care. An end of study clinical MRI of the cervical spinal cord with
and without contrast will be recommended to study participants at week 96 as medical standard
A Multicenter, Observational, Open-Label, Single-Arm Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JCV Antibody Negative Patients
Multiple studies have demonstrated the positive effect of early therapy on patients who were in the earliest stages of relapsing-remitting multiple sclerosis (RRMS; having 1 clinical event clinically isolated syndrome [CIS] and magnetic resonance images [MRIs] suggestive of MS). These studies involved partially effective medications, all with approximately a 30% reduction in relapse rate.Tysabri is a monoclonal antibody that binds and interferes with the action of 41 integrin which results in reducing certain cells of the immune system transmigration across the blood brain barrier.In the recently presented Tysabri Observational Program (TOP) data, early treatment was most effective in treatment-nave patients and patients with lower Expanded Disability Status Scale (EDSS) scores. Thus, use of an effective agent (Tysabri) in the early stages of MS (when immune cell collections have not yet developed behind the blood-brain barrier [BBB]) may be beneficial, and has not been systematically studied.Study population includes RRMS patients diagnosed with Mc Donald's Criteria, Age 18 to 45 years old, Anti-JCV antibody negative test within 6 months of Screening Visit or negative test for anti-JCV antibody at Baseline Visit.Methodology:This is a Phase 4, single-country, multicenter, open-label, prospective, observational study.The primary objective of the study is to determine which baseline and yearly response factors (clinical and para clinical) predict overall disease-free status at Month 12 and Month 24, and clinical disease-free status in subsequent Months 36 and 48. The response factors include clinical assessments of sustained EDSS progression, relapse status, and MRI measures, and patient reported outcomes (PROs) of cognition, capacity to work, quality of life (QoL), and visual function assessments.In general, continuous variables will be presented with summary statistics (mean, standard deviation, median, range), and categorical variables will be presented with frequency distributions. All analyses will be conducted using 2-sided tests at the type I error rate (alpha level) of 0.05 unless otherwise stated.There will be up to 10 clinic visits included in this protocol. A patients participation in the study will last up to 48 months.
Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)
This study is complementary to a multi-center, randomized, double-blind,parallel-group,
placebo-controlled, variable treatment duration study comparing the efficacy and safety of
BAF312 to placebo in patients with SPMS (NCT01665144). Investigators will explore both
immunological and neuroprotective mechanisms of BAF312 (siponimod), a novel agent in the
setting of a SPMS clinical trial.
This study is part of a multi-center study, with the University of Michigan serving as the