A Systems Approach to Understanding Disease Processes in Multiple Sclerosis

NCT05081700 | Completed

• 1 other identifier: ISB_PHS 2019-01
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This pilot study will establish a proof of concept for using a systems biology approach to characterize the dynamics of MS disease processes. The primary objective of the study is to identify multi-omic (genetic, proteomic, biochemical and/or microbial) factors that correlate with clinical and subclinical MS disease activity. Identification of such biomarkers could have an immediate clinical utility in identification of MS patients prone to more aggressive disease earlier in their disease course, thus affording the opportunity to better individualize therapy. In addition, insights from better understanding of the complex interplay of various systems biology factors should improve our understanding of MS in general. The study will recruit 14 patients with relapsing MS who are initiating treatment with ocrelizumab, and follow them for 30 months.

Conditions

Multiple Sclerosis

Keywords

multi-omic factors

Outcome Measures

Primary Outcomes (1)

• Proportion of relapse free patients

  Number of participants free of MS relapse at 6, 12, and 30 months divided by total number of participants.

  6, 12, and 30 months

Secondary Outcomes (10)

• Annualized relapse rate (ARR)

  12 and 30 months

• Correlates of T2 lesions on-study MRI activity

  12, 24, and 30 months

• Correlates of gadolinium enhancing lesions on-study MRI activity

  12, 24, and 30 months

• Expanded Disability Status Scale (EDSS)

  12 and 30 months

• Timed 25-Foot Walk (T25FW)

  6, 12, and 30 months

Other Outcomes (5)

• Whole genome sequencing

  6, 12, and 30 months

• Blood analysis plasma

  6, 12, and 30 months

• Blood analysis serum

  6, 12, and 30 months

Study Arms (1)

Patients with relapsing MS

Patients with relapsing remitting MS who are intending to receive ocrelizumab.

Drug: All patients in the study will be treated with ocrelizumab

Interventions

All patients in the study will be treated with ocrelizumab DRUG

300 mg of OCR IV infusion will be given on Day 0 followed by a second dose of 300 mg OCR 14 days later ± 2 days, and then 600 mg of OCR as a single infusion will be given every 24 weeks thereafter per standard medical care.

Also known as: OCREVUS

Patients with relapsing MS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Study patients will be recruited from the population of relapsing MS patients initiating treatment with ocrelizumab, who are being followed at the Swedish MS Center in Seattle, Washington and the Providence MS Center in Portland, Oregon. MS population and a reference non-MS population

You may qualify if:

• Able to understand the purpose and risk of the study and provide written informed consent.
• Male or female patients aged 18 to 60, inclusive at time of consent, who meet FDA approved indications to receive ocrelizumab treatment.
• Have a definite diagnosis of relapsing MS (RMS) (Lublin et al. 2014).
• Screening EDSS ≤ 5.0.
• Have a length of disease duration since disease symptom onset ≤ 15 years.
• Documentation of 1 or more on-DMT relapses, or 1 brain MRI revealing new or enlarged T2 lesion(s) over the 2 years prior to the screening visit (this could include DMT naïve patients).
• Patient does not have any clinically significant medical conditions based on medical history, physical examination, and laboratory screening, as defined by the investigator, which would interfere with the conduct of the study.
• Patient is willing and able to comply with the protocol assessments and visits, in the opinion of the investigator.
• For women of childbearing potential: agreement to use an effective birth control method and avoid breastfeeding during the study period, and for those patients who have received ocrelizumab, for at least 6 months after the last dose.
• Able to understand the purpose and risk of the study and provide written informed consent.
• Have participated in the core study and continue to receive ocrelizumab.
• Have not passed week 120±14 days post initial ocrelizumab dose in the core study.
• Diagnosis of relapsing MS at time of consent.
• Patient is willing and able to comply with the protocol assessments and visits, in the opinion of the investigator.
• For women of childbearing potential: agreement to use an effective birth control method and avoid breastfeeding during the study period and for at least 6 months after the last dose of ocrelizumab.

You may not qualify if:

• Diagnosis of progressive MS at screening.
• Patient is unable to undergo MRI with gadolinium contrast imaging for any reason.
• Known presence of other neurological disorders, including but not limited to, the following:
• History of cerebrovascular disorders.
• History or known presence of CNS tumor.
• History or known presence of potential metabolic causes of myelopathy.
• History of peripheral neuropathy.
• History or known presence of infectious disease of the CNS.
• History of genetically inherited CNS degenerative disorder.
• Neuromyelitis optica spectrum disorder, anti-Aquaporin 4 IgG, or Anti-MOG IgG .
• History of progressive multifocal leukoencephalopathy (PML).
• History or known presence of any other concurrent systemic or nervous system autoimmune disorders, potentially causing progressive neurologic disease.
• History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression).
• Pregnancy or lactation.
• Chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.

Sponsors & Collaborators

• Providence Health & Services: lead
• Institute for Systems Biology: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Providence Neurological Specialties West

Portland, Oregon, 97225, United States

Location

Swedish Medical Center Multiple Sclerosis Center

Seattle, Washington, 98122, United States

Location

Related Publications (7)

• Ontaneda D, Thompson AJ, Fox RJ, Cohen JA. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet. 2017 Apr 1;389(10076):1357-1366. doi: 10.1016/S0140-6736(16)31320-4. Epub 2016 Nov 24.

  PMID: 27889191 BACKGROUND

• Steinman L, Zamvil SS. Beginning of the end of two-stage theory purporting that inflammation then degeneration explains pathogenesis of progressive multiple sclerosis. Curr Opin Neurol. 2016 Jun;29(3):340-4. doi: 10.1097/WCO.0000000000000317.

  PMID: 27027554 BACKGROUND

• Fraussen J, de Bock L, Somers V. B cells and antibodies in progressive multiple sclerosis: Contribution to neurodegeneration and progression. Autoimmun Rev. 2016 Sep;15(9):896-9. doi: 10.1016/j.autrev.2016.07.008. Epub 2016 Jul 7.

  PMID: 27396817 BACKGROUND

• Price ND, Magis AT, Earls JC, Glusman G, Levy R, Lausted C, McDonald DT, Kusebauch U, Moss CL, Zhou Y, Qin S, Moritz RL, Brogaard K, Omenn GS, Lovejoy JC, Hood L. A wellness study of 108 individuals using personal, dense, dynamic data clouds. Nat Biotechnol. 2017 Aug;35(8):747-756. doi: 10.1038/nbt.3870. Epub 2017 Jul 17.

  PMID: 28714965 BACKGROUND

• Hellberg S, Eklund D, Gawel DR, Kopsen M, Zhang H, Nestor CE, Kockum I, Olsson T, Skogh T, Kastbom A, Sjowall C, Vrethem M, Hakansson I, Benson M, Jenmalm MC, Gustafsson M, Ernerudh J. Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis. Cell Rep. 2016 Sep 13;16(11):2928-2939. doi: 10.1016/j.celrep.2016.08.036.

  PMID: 27626663 BACKGROUND

• Hakansson I, Tisell A, Cassel P, Blennow K, Zetterberg H, Lundberg P, Dahle C, Vrethem M, Ernerudh J. Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis. Eur J Neurol. 2017 May;24(5):703-712. doi: 10.1111/ene.13274. Epub 2017 Mar 6.

  PMID: 28261960 BACKGROUND

• Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, Kanner R, Bencosme Y, Lee YK, Hauser SL, Crabtree-Hartman E, Sand IK, Gacias M, Zhu Y, Casaccia P, Cree BAC, Knight R, Mazmanian SK, Baranzini SE. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10713-10718. doi: 10.1073/pnas.1711235114. Epub 2017 Sep 11.

  PMID: 28893978 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and stool samples will be analyzed for genetic and biochemical assay program including a whole genome sequence, advanced blood chemistry tests including heavy metals, proteins \& metabolites, profiling of over 1000 low molecular weight metabolites and 29 fatty acids from blood plasma, measurement of nearly 200 serum proteins that constitute the neurology and inflammation panels of the O-link assay system, a description of the gut microbiome based on analysis of 16S ribosomal RNA sequences and serum immunoglobulin panel (IgG, IgM, and IgA).

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Stanley Cohan, MD, PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: October 18, 2021
• Study Start: May 11, 2020
• Primary Completion: June 27, 2023
• Study Completion: November 3, 2023
• Last Updated: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)