43 Clinical Trials for Various Conditions
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis
A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.
This study will evaluate the efficacy and safety of ocrelizumab ( Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study focuses on upper limit disability progression. This study will consist of the following phases: screening, double-blind treatment, follow-up 1 (FU1), an optional open-label extension (OLE), follow-up 2 (FU2), and B-cell monitoring (BCM).
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the safety, tolerability and activity of ibudilast administered twice daily over a 96 week period in subjects with primary or secondary progressive multiple sclerosis who are currently untreated with long-term MS disease modifying therapy (DMT) or who are receiving either glatiramer acetate (GA) or interferon beta-1, any formulation (IFNβ-1A \[Avonex, Rebif\] or IFNβ-1B \[Betaseron, Extavia\]). Study drug or placebo will be administered to a total of 250 male and female subjects from 21 to 65 years old, inclusive, in two treatment groups. Randomization of subjects will be stratified by disease status (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) and immunomodulating therapy status: current use of immunomodulating therapy or no current use of immunomodulating therapy. The study will consist of a screening phase (up to 30 days) followed by a treatment phase (96 weeks) and a follow-up visit (1 month post Week 96 visit). Following the screening phase, subjects who continue to meet entry criteria will be randomly assigned to 1 of 2 treatment groups: doses up to ibudilast 100 mg/day or matching-placebo in a 1:1 ratio. Study drug will be administered twice daily (BID), e.g., ibudilast 50 mg or placebo taken in the morning and evening).
This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo.
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis
All males and females between 18-70 years of age regardless of their race and ethnicity with a confirmed diagnosis of Primary Progressive Multiple Sclerosis (PPMS), Secondary Progressive Multiple Sclerosis (SPMS), and Relapse Remitting Multiple Sclerosis (RRMS) are invited to participate in this Observational study being conducted across four sites in the US. Since this is an observational study no medication/drug or treatment will be given to the participants. The investigator will be collecting information about the participant's MS disease, its progression, current medications, radiographic scans, and blood samples. This will help the investigator evaluate the biomarkers and new treatment options to better understand the MS disease process.
The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with chronic inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments. No reparative therapies exist for the treatment of multiple sclerosis. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at the University of California, San Francisco (UCSF). Following in vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of multiple sclerosis in the context of chronic optic neuropathy. That pilot study was recently completed and is the first randomized control trial documenting efficacy for a putative remyelinating agent for the treatment of MS. The preselected primary efficacy endpoint (visual evoked potential) was met and a strong trend to benefit was seen for the principal secondary endpoint assessing function (low contrast visual acuity). That trial number was 13-11577. This study seeks to follow up on that study and examine clemastine fumarate's protective and reparative effects in the context of chronic demyelinating brain lesions as imaged by multi-parametric MRI assessments. The investigators will be assessing the effects of clemastine fumarate as a remyelinating therapy and assessing its effect on MRI metrics of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis. In addition to using conventional multi-parametric MRI assessments, this study will also evaluate a new MRI technique called Ultrashort Echo Time (UTE) MRI to assess the effects of clemastine fumarate as a remyelinating therapy of chronic lesions found in patients with a confirmed diagnosis of relapsing-remitting multiple sclerosis and compare it to the other assessments.
This study is being conducted to investigate risk factors for disability progression in Multiple Sclerosis and related disorders (MSRD). The primary goal is to assess whether combining information from visual assessment, blood markers, as well as historical and ongoing longitudinal MRIs of the brain, orbit (the part of the skull where eyes are located), and/or spinal cord can predict changes in quantitative disability measures related to MSRD and neurological disease.
This study evaluates the effectiveness of N-acetyl cysteine (NAC) in the treatment of progressive multiple sclerosis. Half of the patients will receive NAC, while the other half will receive a placebo.
This study will evaluate if giving insulin that is administered in the nostrils (intranasal) is safe and tolerable for people with multiple sclerosis (MS). It is also being done to evaluate if intranasal insulin improves cognitive function in people with MS and to evaluate how it might be working.
This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS. The study will be conducted in two cohorts i.e. RMS cohort (4 arm group) and PPMS cohort (one arm group). RMS cohort: Ocrelizumab will be administered as two intravenous (IV) infusions of 300 milligrams (mg) on Days 1 and 15. Subsequent doses will be given as single 600-mg infusions at Weeks 24 and 48. Participants will be randomized in 1:1:1 ratio to receive lumbar puncture (LP) post-treatment at Week 12, 24, or 52 following the first dose of ocrelizumab in three arm groups. A fourth RMS arm with delayed treatment start (Arm 4 \[control group\]) will not be a part of the randomization and will be recruited separately, wherein treatment with ocrelizumab will be delayed for 12 weeks from pre-treatment baseline. PPMS cohort: Ocrelizumab 600 mg will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks. Participants will receive a LP at the start of the study before dosing with ocrelizumab and second LP at Week 52 following the first dose of ocrelizumab. A long-term extension will be conducted for participants that complete the study and continue to receive ocrelizumab. Treatment with ocrelizumab in the entire study will continue for approximately 4.5 years after the first infusion.
This study will evaluate the safety and tolerability of synthetic T3, liothyronine. It will establish if there are changes in MS symptoms and if there is a positive effect on markers of neuronal health.
The study will use a multimodal therapeutic lifestyle intervention consisting of a study diet, stressing more vegetables and fruit, elimination of foods at greatest risk for food allergy, meditation, self massage, progressive exercise and neuromuscular electrical stimulation for rehabilitation of gait and fatigue disability in the setting of secondary and primary progressive multiple sclerosis with gait disability.
This study is a prospective Phase 1a open-label single- center trial. It will assess the safety of intrathecal administration of DUOC-01 cells to adults with Primary Progressive Multiple Sclerosis (PPMS). DUOC-01 is a population of cells expanded from donated human umbilical cord blood cells and is intended for treatment of neurodegenerative and demyelinating diseases. There will be approximately 20 participants enrolled. Exploratory objectives include changes in MS assessment scores, changes in brain MRI findings, and changes in blood biomarkers.
This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.
Primary Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in primary progressive multiple sclerosis (PPMS) Secondary Objectives: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 in PPMS and its relationship to efficacy and safety To evaluate pharmacodynamics of SAR442168
This study is an open-label, non-randomized study to evaluate rate and severity of infusion-related reactions (IRRs) of ocrelizumab infused over a shorter time period than the approved administration rate in participants with PPMS or RMS in the United States (U.S.). Participants will be enrolled into two cohorts. Cohort 1 will examine the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. This cohort will consist of patients who have already received one or two doses of ocrelizumab according to the approved infusion protocol (i.e., per the currently U.S. label) and have reported no serious IRRs and who will then receive the next infusion of ocrelizumab at a higher rate in order to deliver 600 mg over the course of approximately 2 hours. Cohort 2 will examine the effect of administering ocrelizumab per a shorter infusion protocol for the second infusion of Dose 1. This cohort will consist of ocrelizumab naïve patients who, after receiving Infusion 1/Dose 1 of ocrelizumab at the approved rate (300 mg over approximately 2.5 hours or longer) have no reported serious IRRs, will then receive the second 300-mg shorter infusion over approximately 1.5 hours.
The primary objective of this expanded access program is to provide ocrelizumab as treatment for eligible participants with primary progressive multiple sclerosis (PPMS) before it is commercially available in the United States (U.S.) for the indication of PPMS.
This Phase 2 study is intended to serve as a proof of concept for potential treatment with laquinimod in patients with PPMS. The study is also aimed at evaluating 2 doses of laquinimod in this population.
Background: - The Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS) trial tested a new drug for multiple sclerosis. In the IPPoMS trial, participants took either idebenone or placebo. Researchers want to give idebenone to all participants for 1 year. It is still not certain whether idebenone can slow the progression of multiple sclerosis, but this study may help answer that question. Objectives: * To provide idebenone to all participants on the IPPoMS trial. * To collect data on the safety and effectiveness of idebenone for primary progressive multiple sclerosis. Eligibility: - Individuals at least 18 years of age who have completed 3 years in the IPPoMS trial. Design: * The first study visit for this trial will happen on the same day as the last visit for the IPPoMS trial. * Participants will provide a blood samples and will have a lumbar puncture. They will also receive a new supply of idebenone to take three times a day with food. They will keep a diary to report on any side effects. * After this first treatment visit, participants will have two follow-up visits to the NIH 6 months apart. These visits may be scheduled over multiple days. Participants will provide blood and urine samples. They will also have imaging studies of the brain and spine. * Participants will have phone calls with the study researchers to provide updates on their condition and any side effects.
The goal of this study is to enroll 100 participants with Primary Progressive Multiple Sclerosis (PPMS) that have joined the MURDOCK Study Horizon 1.5 (Duke IRB Pro00011196) and the Multiple Sclerosis cohort (Duke IRB Pro00023791). All 100 participants will complete a biannual collection of a follow up questionnaire and blood/urine collection for a period of 5 years.
Background: * Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that progressively weakens and destroys the pathways of the nervous system. About 10 percent to 15 percent of patients develop primary-progressive MS (PP-MS), characterized by progressive accumulation of disability from the disease onset, without any marked improvements or relapses. There are currently no effective treatments for PP-MS. * Idebenone is a manmade drug that is similar to a naturally occurring compound known as coenzyme Q10, a common dietary supplement. Research data suggest that idebenone may be able to limit demyelination and death of brain cells and thereby slow or halt the progression of neurological dysfunction such as that occurring in MS. Objectives: - To evaluate the safety and effectiveness of using idebenone to treat primary progressive MS. Eligibility: - Individuals between 18 and 65 years of age who have been diagnosed with primary progressive multiple sclerosis. Design: * The study will last 3 years and will be divided into two parts: a 1-year pretreatment baseline and 2 years of treatment with either idebenone or a placebo. * Pre-treatment study: approximately 5 clinic visits over 1 year. * Visit 1: Comprehensive medical history and neurological examination, with brain scans and neurological tests. * Visit 2: Magnetic resonance imaging (MRI) scan of the spine and lymphocytapheresis (withdrawal of white blood cells for testing). * Visit 3: Lumbar puncture. * Visit 4: Skin biopsy. * Visit 5: Repeat MRI of the brain and spinal cord, as well as neurological tests; these tests will be scheduled over 2 days. * After the five pretreatment visits, patients will receive a 6-month supply of study medication (either idebenone or a placebo) to take three times a day with food * Patients will continue to have regular followup clinic visits with brain MRI scans, blood tests, and other evaluations of brain and nervous system function. Randomly selected participants will have additional MRI scans for further safety precautions.
The goal of this non-interventional, observational study is to learn if cortical plexus enhancement in patients with primary progressive multiple sclerosis occurs in response to the autoimmune inflammatory process.
The goal of this non-interventional, observational study is to determine whether cortical pathology can be slowed down by use of ocrelizumab.
The investigators propose to use the novel SV2a-PET ligand, \[F-18\]SDM-8 to assess synaptic density in progressive MS (including primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS)) as compared to relapsing-remitting multiple sclerosis (RRMS) patients and healthy controls, given its improved imaging characteristics and potential for large scale applicability. The specific aims of the study are: Aim 1: To compare the cortical and subcortical grey matter synaptic density in progressive MS patients, patients with relapsing-remitting MS, and healthy subjects, using a novel \[F-18\] labeled synaptic density PET ligand, \[F-18\]SDM8, also known as \[F-18\]SynvesT-1. Aim 2: To compare the relationship of synaptic density PET and standard 3T MRI measures including global and regional brain atrophy and lesion load with clinical measures of physical disability, cognitive impairment, fatigue and depression in MS patients. Aim 3: To assess the relationship of synaptic density PET with serum neurofilament light chain (NfL) and with serum measurements of inflammatory markers, IL-1β, TNF-α, IL-6, MCP-1 (Monocyte Chemoattractant Protein-1) and MIF-1 (Macrophage Migration Inhibitory Factor-1).
The purpose of this study is to evaluate the safety and tolerability of ATA188 as a monotherapy in Parts 1 and 2, to determine the recommended Part 2 dose (RP2D) of ATA188 as monotherapy in Part 1, and to evaluate the effect of ATA188 treatment on clinical disability, as assessed by confirmed Expanded Disability Status Scale (EDSS) improvement at 12 months in Part 2 in participants with progressive forms of multiple sclerosis (MS) (primary progressive multiple sclerosis \[PPMS\] and secondary progressive multiple sclerosis \[SPMS\]).
Participants will receive intensive therapy through a video game in their own homes for 1 month. The game is operated by movements of the body (no controller needed) and acts like a virtual therapist. Participants will agree to play the game for 30 hours. They will also receive 4 home visits from a therapist designed to increase use of their arm for daily activities that are important to them. Participants will also receive a smart watch that will measure use of their weaker arm and alert them when their arm is not participating in activities. Arm strength and function will be measured before and after the therapy program.
Multiple sclerosis (MS) is a chronic inflammatory disorder affecting the central nervous system that is characterized pathologically by focal demyelinating lesions in the brain parenchyma. Meningeal inflammation in MS was first noted in 2004. Ectopic lymphoid follicles were described in the meninges of patients with secondary progressive MS (SPMS) and were thought to correlate with cortical lesions and atrophy (a surrogate marker for disability). Subsequently, inflammation in the meninges has been described in primary progressive MS (PPMS) as well as early relapsing MS. The ectopic lymphoid follicles are composed of B-cells, T follicular helper cells and follicular dendritic cells. Rituximab is a monoclonal antibody against CD-20 (a B-cell marker) that is FDA approved for the treatment of various lymphomas. Intrathecal (IT) rituximab administration has been used in central nervous system (CNS) lymphoma to achieve greater cerebrospinal fluid (CSF) concentrations of rituximab. In MS, IT administration of rituximab could lead to higher CSF rituximab levels resulting in the disruption of meningeal ectopic lymphoid follicles, ultimately reducing cortical lesions and possibly disease progression. The investigators hypothesize that IT rituximab therapy in patients with progressive forms of MS could disrupt ectopic lymphoid follicles in the meninges and thus slow progression of the disease, which is particularly important because there exist no FDA-approved therapies for progressive MS. The investigators hypothesize that using magnetic resonance imaging (MRI) to identify those with enhancing meningeal lesions will provide a biomarker to select patients who might be most likely to respond to IT rituximab and to use these lesions to monitor therapeutic response. The primary aim of this study is to assess the safety of intrathecal administration of rituximab in patients with progressive MS. The secondary aims are to evaluate if IT rituximab leads to a decrease in the quantity of meningeal lesions on MRI or to changes in biomarkers of inflammatory activity or neuronal injury in the CSF.
The purpose of this study is to evaluate whether FTY720 is effective in delaying MS disability progression compared to placebo in patients with PPMS. This was an open-label, single-arm extension study to a double-blind, randomized multicenter, placebo-controlled, parallel-group core study. The core study completed and eligible patients enrolled into the extension study at the next scheduled or unscheduled core study visit. All patients, regardless of their treatment in the core study, received fingolimod 0.5 mg in the extension study. The extension study was terminated early after the results of the core study became available showing that the study did not meet its primary endpoint which was defined as confirmed disability progression in this population