Active clinical trials for "Sclerosis"

FDA-approved multiple sclerosis (MS) disease-modifying therapies (DMTs) target the relapsing phase of MS but have minimal impact once the progressive phase has begun. It is unclear if, in the relapsing phase, there is an advantage of early aggressive therapy with respect to preventing long-term disability. The infectious risks and other complications associated with higher-efficacy treatments highlight the need to quantify their effectiveness in preventing disability. The TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial is a pragmatic, randomized controlled trial that has two primary aims: 1) to evaluate, jointly and independently among patients deemed at higher risk vs. lower risk for disability accumulation, whether an "early aggressive" therapy approach, versus starting with a traditional, first-line therapy, influences the intermediate-term risk of disability, and 2) to evaluate if, among patients deemed at lower risk for disability who start on first-line MS therapies but experience breakthrough disease, those who switch to a higher-efficacy versus a new first-line therapy have different intermediate-term risk of disability.

The etiologic mechanisms involved in multiple sclerosis (MS) are not yet fully understood. Indeed MS is a multifactorial disease involving genetic and environmental factors and Epstein-Barr-Virus (EBV) could be one of these factors. However the link between EBV infection and the immunological mechanisms underlying MS is not clear. Robust sero-epidemiological evidences support an association between EBV infection and MS, and immunological data suggest an altered/deficient immune response against this virus. In healthy individuals EBV produces a persistent infection that is tightly controlled by the immune system. In patients with MS, cellular and humoral immune studies demonstrate an altered response against the virus with a T-cell abnormal reactivity against the EBV-infected autologous B-cells, elevated humoral immune response to Epstein Barr Nuclear Antigen-1, and in the case of children, an increased EBV shedding, demonstrating frequent EBV reactivations. Thus, it has been proposed, that patients with MS present a partially inefficient control of the EBV infection. Some experimental data support the hypothesis suggesting that the presence of autoreactive EBV-B cells in the meninges of patients, probably due to an insufficient clearance of these cells by the immune system, lead to the infiltration of autoreactive T cells. Another hypothesis also suggests a deficient control of the virus, in that case during the inactive phase of the disease. Together, the above data and hypotheses lead to the notion that an immune intervention capable of restoring the host-EBV balance could be beneficial to MS patients In this project, we will assess the feasibility and safety of autologous transfer of several amounts of CD8 T cells directed against autologous EBV transformed B cell lines, in order to finally restore an efficient control of EBV in MS patients. The main objective of the project is to test the feasibility and safety of the process, while efficacy parameters will be also assessed in secondary objectives.

The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials. To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.

Ocrelizumab is a humanized anti-CD20 monoclonal antibody that showed in phase III trials a powerful effect on relapse rate and lesion load accumulation in the relapsing form of multiple sclerosis (RMS). This therapeutic agent also showed for the first time a significant reduction of disability progression in Primary Progressive Multiple Sclerosis (PPMS) patients, whereas all other anti-inflammatory drugs had failed to do so in well-conducted studies. This raises the possibility that ocrelizumab, beyond its effects on the adaptive immune system activation underlying white matter lesions and clinical relapses, could beneficially influence other mechanisms involved in the progressive phase of the disease, such as the innate immune microglial cells activation, that has been described to persist in a diffuse manner in the Central Nervous system (CNS). To date the activation of these cells is not accessible to classical Magnetic Resonance Imaging (MRI) techniques, impeding the full investigation of the therapeutic efficacy of drugs such as ocrelizumab.

The DELIVER-MS study seeks to answer the question: Does early treatment with highly effective DMT improve the prognosis for people with MS? This is an area of significant controversy and no data currently exist to guide treatment choices for patients and clinicians. The study results will help guide overall treatment philosophy and will be applicable not only to a wide range of existing therapies but also to new therapies, meeting a significant unmet need in patient decision making and aiding the decision for medication approval by third parties.

This is a 52 week, single center, randomized, double-blind, placebo-controlled study. After patients maintain a stable dose of Mycophenolate Mofetil (MMF) for at least 1 month, they will be randomized to treatment with either Belimumab & Rituximab or placebo.Patients in both groups will be on background MMF for the entirety of the study. Belimumab will be administered subcutaneously and Rituximab intravenously. Placebo injections and infusions will be of normal saline. Randomization will be done in a 2:1 manner to favor the treatment group. It is hypothesized that that Rituximab and Belimumab combination therapy with Mycophenolate Mofetil background therapy will improve fibrosis in SSc skin when compared to treatment with placebo and Mycophenolate Mofetil in a group of patients with early dcSSc.

Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NTZ) is used in the treatment of relapsing multiple sclerosis (MS). The risk of PML increases after 18 months of treatment. When switching from NTZ to another disease modifying treatment (DMT) in these MS patients with an active disease, there is a high risk of inflammatory reactivation. Nonetheless, a washout period of several weeks is necessary before initiating a new DMT. The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).

This study will evaluate the safety, tolerability, and descriptive efficacy of BIIB017 in pediatric participants with relapsing-remitting multiple sclerosis (RRMS) and to assess the pharmacokinetics (PK) of BIIB017 in pediatric participants with RRMS in Part 1. In Part 2, the study will evaluate the long-term safety of BIIB017 and further describe safety and the long-term multiple sclerosis (MS) outcomes after BIIB017 treatment in participants who completed the study treatment at Week 96 in Part 1 of the study.

This study consists of a phase 1 part and a phase 2 part. Phase 1 part: This is a phase 1, open-label, multicenter, dose escalation study to evaluate the safety and tolerability of bosutinib to determine the maximum tolerated dose(MTD) and a recommended phase 2 dose (RP2D) of bosutinib for treatment of ALS patients. Also, efficacy will be evaluated exploratory. Phase 2 part: This is an open label, multicenter, phase 2 part whose purpose is to evaluate the efficacy exploratorily and the long-term (for 24 weeks) safety of bosutinib for the treatment of ALS patients.

Systemic sclerosis (SSc) is a rare and potentially life-threatening autoimmune disorder with a significant impact on health and quality of life. The non-pharmacological interventions address to psychological sequalae currently available are limited and have poor efficacy. Well-Being Therapy (WBT) is a brief psychotherapy which has shown efficacy in decreasing the relapse rates of depression in adults, in generalized anxiety disorder and in cyclothymia. WBT has never been tested in SSc and it might represent a useful complementary therapeutic option to improve SSc patients' well-being. The aim of the present study is to evaluate the psychological status of the SSc patients and to test the efficacy of WBT in a sample of SSc patients if compared to a control condition.