Multiple Sclerosis clinical trials at UCSF

This is a Phase IIIb, single-arm, multicenter, OLE study. Participants receiving ocrelizumab as an investigational medicinal product (IMP) in a Roche sponsored Parent study who continue to receive ocrelizumab or are in safety follow-up at the time of the closure of their respective Parent study (WA21092, WA21093 or WA25046) are eligible for enrollment in this extension study. Participants who will continue ocrelizumab treatment will receive IMP based on the dosage and administration received at the time of rollover from the Parent study.

The goal of this study is to test a drug called KYV-101 in people who have progressive multiple sclerosis (MS) and who have not responded to standard therapies to slow disease progression. The main questions it aims to answer are: - What is the highest therapy dose that can be given without causing harm? - Can this therapy enter the central nervous system? Participants will be asked to: - Attend 14 visits plus an 8-day inpatient hospital stay over the course of 58 weeks. - Complete apheresis and chemotherapy treatments in preparation for KVY-101 therapy. - Undergo medical and research testing such as physical and neurological exams, MRI, lumbar puncture, blood draws, questionnaires, and vision assessments.

This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in participants with progressive multiple sclerosis (PMS).

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with acute inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments. No reparative therapies exist for the treatment of acute demyelinating lesions. 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 acute 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 lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination. 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 acute lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination and compare it to the other assessments.

In this Phase 1b open-label prospective clinical trial, patients with relapsing-remitting MS will undergo FMT of FMP30 (donor stool) via colonoscopy and immunological efficacy endpoints will be assessed at various time points. The active phase of the study will continue for 12 weeks post-FMT with safety and biomarker (engraftment) follow-up for 48 weeks. A parallel observational control arm of MS patients who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. The study duration for the Observational Control Arm is 12 weeks.

Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment favorably alters CSF markers of chronic inflammation.

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.

This study is structured around three main aims. In Aim 1, investigators will conduct community-based participatory research (CBPR) to develop culturally tailored methods to assess childhood adversity in multiple sclerosis (MS). Aim 2 will investigate the impact of childhood adversity on MS outcomes among individuals with relapsing-remitting MS (RRMS), among whom 70% belong to a group historically under-represented in MS research: Black, Hispanic, or poverty-impacted. Aim 2 procedures involve two visits that include a research blood draw and an MRI scan. In Aim 3, investigators will conduct interviews and surveys to explore environmental and social factors affecting quality of life for minority MS patients.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Diagnosis is established by clinical assessment of persons with MS (PwMS), in combination with imaging and body fluid assessments. Treatment decisions in MS are mainly based on periodic monitoring of disease activity and progression through clinical and imaging assessments. The predictive and prognostic value of currently used assessments to individualize treatment decisions is still very limited. Emerging digital measures have the potential to provide granular health status measurements that would allow monitoring MS disease activity and progression continuously and remotely, in real-world settings, with minimal disruption of patients' life. Using the investigators' self developed dreaMS software program the investigators previously identified digital biomarkers (DB) that hold promise to provide detailed and accurate assessments of MS-related health status and disease progression to complement traditional clinical, imaging, or body fluid assessments. This international, observational study aims to evaluate and validate the generalizability of these DB across different languages and cultural settings to provide DB that are helpful for patient care, research, and regulatory decisions. Beyond this, the processes and data structures created for this study are intended to establish a collaborative research platform for subsequent studies, including pragmatic trials, promoting new long-term international academic collaborations.