DUOC-01 for Multiple Sclerosis

(DUOC for MS Trial)

Overseen By Erin Arbuckle

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joanne Kurtzberg, MD

Must be taking: Disease-modifying therapies

Must not be taking: Immunosuppressive medications, Cytotoxic chemotherapy

Disqualifiers: Other neurological disorders, HIV, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called DUOC-01 for individuals with Primary Progressive Multiple Sclerosis (PPMS). The goal is to determine if DUOC-01, derived from special cells in donated umbilical cord blood, is safe when administered directly into the spine. The study will also examine changes in MS symptoms and brain health. Individuals with a stable MS condition without major recent changes might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how DUOC-01 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I have to stop taking my current medications for the trial?

No, you don't have to stop taking your current medications. Participants on disease-modifying therapies must continue them during the study, although changes can be made if needed for clinical reasons.

Will I have to stop taking my current medications?

The trial requires that participants continue their current disease-modifying therapies throughout the study, unless there are clinical reasons to change them, which would be decided by the clinician.

Is there any evidence suggesting that DUOC-01 is likely to be safe for humans?

Research shows that DUOC-01 is being tested for safety in people with Primary Progressive Multiple Sclerosis. This treatment uses cells from donated umbilical cord blood. So far, studies with similar treatments have not reported any major safety issues. However, like any new treatment, some risks may still exist.

As this is an early trial, the main goal is to ensure DUOC-01 is safe for humans. The study will monitor side effects at different doses. The trial's phase indicates that while the treatment is still new, researchers consider it safe enough for human testing. This suggests some confidence in its safety, but it remains under close observation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple sclerosis, which often involve immunomodulatory drugs, DUOC-01 is unique because it uses an intrathecal infusion of stem cells. This new approach involves delivering DUOC-01 directly into the spinal fluid, potentially offering a more targeted and effective method to repair damaged nerve tissues. Researchers are particularly excited about the potential for DUOC-01 to promote neuroregeneration, which could slow or even reverse disease progression, offering new hope for patients with this challenging condition.

What evidence suggests that DUOC-01 might be an effective treatment for Multiple Sclerosis?

Research has shown that DUOC-01, a treatment derived from human umbilical cord blood cells, holds promise in early studies. In past animal research, DUOC-01 repaired the protective coating around nerve fibers, reduced brain inflammation, and decreased damage from immune cells. These effects suggest potential benefits for diseases like Primary Progressive Multiple Sclerosis (PPMS), where the immune system attacks the nervous system. Although more human research is necessary, these early findings offer hope for its potential effectiveness in people. Participants in this trial will receive DUOC-01 through an intrathecal infusion, with varying dosages studied across different cohorts. ^{1 2 3 6 7}

Who Is on the Research Team?

Beth Shaz, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults aged 18-65 with Primary Progressive Multiple Sclerosis (PPMS) and an EDSS score of 3.0-6.5 are eligible for this trial. Participants must have stable MS, a matched umbilical cord blood unit available, and agree to effective contraception during the study plus six months after treatment. Exclusions include prior transplants or cell therapies within three years, other progressive neurological disorders, recent malignancies except certain skin cancers, active immune diseases besides MS, MRI or lumbar puncture contraindications, severe infections, ventilatory support need, recent suicidal behavior or ideation.

Inclusion Criteria

My disability score is between 3.0 and 6.5, and it has been stable for the last 6 months.

I have been diagnosed with primary progressive MS.

Able to complete a written informed consent prior to any study assessments

Exclusion Criteria

I have not had a severe infection in the last 2 weeks.

I have seizures that medication cannot control.

Pregnant or breastfeeding or intention to become pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Manufacturing and Preparation

Production, testing, and release of DUOC-01 cells

19-21 days

Treatment

Intrathecal administration of DUOC-01 cells with monitoring

1 day

1 visit (in-person, hospital stay for 24-hour observation)

Initial Follow-up

Virtual visit to evaluate for adverse events

2 weeks

1 visit (virtual)

Extended Follow-up

Follow-up visits with functional evaluation, biomarker sampling, and brain MRI

12 months

3 visits (in-person at 3, 6, and 12 months)

What Are the Treatments Tested in This Trial?

Interventions

• DUOC-01

Trial Overview The trial is testing DUOC-01 cells administered intrathecally (into the spinal canal) to treat PPMS. DUOC-01 is derived from human umbilical cord blood cells aimed at treating neurodegenerative conditions. This Phase 1a open-label single-center study will enroll about 20 participants and explore changes in MS scores, brain MRI results, and blood biomarkers.

How Is the Trial Designed?

Group I: DUOC-01 Experimental Treatment 1 Intervention

Intrathecal Infusion of DUOC-01 and hydrocortisone. Cohort 1: 10 million cells Cohort 2: greater than 10 to 25 million cells Cohort 3: greater than 25 to 50 million cells

Who Is Running the Clinical Trial?

Joanne Kurtzberg, MD

Lead Sponsor

Trials

19

Recruited

710+

Published Research Related to This Trial

In a study of 51 multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) for 6 months, those who remained stable showed significantly lower levels of circulating lymphocytes and specific T and B cell subsets compared to those with active disease.

The reduction in CD8+ T cells and CD19+ B cells, along with an increased CD4/CD8 ratio, may serve as predictive markers for treatment response to DMF, indicating that changes in immune cell profiles are clinically relevant for assessing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS. Fleischer, V., Friedrich, M., Rezk, A., et al.[2022]

In a study of 43 patients with relapsing multiple sclerosis (MS) receiving dimethyl fumarate (DMF) for 15 weeks, DMF was found to significantly alter the immune profile by reducing pro-inflammatory B cells and increasing regulatory B cells, suggesting a shift towards a more anti-inflammatory state.

The immunomodulatory effects of DMF varied between patients receiving it as a first-line versus second-line therapy, indicating that previous treatments and disease stage can influence how patients respond to DMF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate as a first- vs second-line therapy in MS: Focus on B cells. Staun-Ram, E., Najjar, E., Volkowich, A., et al.[2022]

Interferon-beta (IFN-β) therapy can significantly reverse the inhibition of oligodendrocyte precursor cell (OPC) proliferation caused by serum from untreated multiple sclerosis (MS) patients, indicating a potential mechanism for its therapeutic effects.

In a longitudinal study of MS patients treated with IFN-β, the reversal of OPC proliferation inhibition was observed after 12 months of treatment, suggesting that the benefits of IFN-β may take time to manifest in terms of cellular regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-β treatment normalises the inhibitory effect of serum from multiple sclerosis patients on oligodendrocyte progenitor proliferation. Kotsiari, A., Voss, EV., Pul, R., et al.[2010]

Ocrelizumab, an anti-CD20 monoclonal antibody, has demonstrated clinical and MRI efficacy in treating both relapsing and primary progressive multiple sclerosis (MS) through three phase III clinical studies.

In cases of aggressive MS, ocrelizumab has shown potential effects on leptomeningeal folliculi, which can be observed in contrast-enhancing MRI images, indicating its ability to target specific areas of inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Additional possible mechanisms of the action of ocrelizumab in multiple sclerosis on example of a case-report]. Boyko, OV., Khoroshylova, II., Petrov, SV., et al.[2019]

In a study involving five patients with chronic progressive multiple sclerosis (MS) and three control patients, dexamethasone treatment for 14 days led to an increase in certain immune cell types (CD3+ and CD4+) in MS patients, indicating a change in immune response.

However, the treatment also highlighted pre-existing immune abnormalities in MS patients, suggesting that while steroids can enhance immune function, their use should be approached with caution due to potential risks in chronic progressive MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of peripheral blood lymphocyte phenotype and function during dexamethazone treatment of progressive multiple sclerosis. Salmaggi, A., Baldetorp, B., Milanese, C., et al.[2019]

In a large study involving 642 participants with progressive multiple sclerosis, MD1003 (high-dose biotin) did not significantly improve disability outcomes or walking speed compared to a placebo over 12 months.

Despite a high incidence of treatment-emergent adverse events in both the MD1003 and placebo groups, the study found no significant safety concerns, but the potential for MD1003 to interfere with laboratory tests raises caution against its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. Cree, BAC., Cutter, G., Wolinsky, JS., et al.[2021]

Dimethyl fumarate (DMF) treatment in patients with relapsing-remitting multiple sclerosis (MS) leads to a significant reduction in total B cell counts, particularly affecting mature memory B cells, which may contribute to its therapeutic effects.

DMF induces an anti-inflammatory shift in B cell responses by reducing the expression of proinflammatory cytokines like GM-CSF, IL-6, and TNF-α, while minimally affecting IL-10 levels, suggesting a novel mechanism for modulating MS disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl Fumarate Treatment Mediates an Anti-Inflammatory Shift in B Cell Subsets of Patients with Multiple Sclerosis. Li, R., Rezk, A., Ghadiri, M., et al.[2022]

Natalizumab, a monoclonal antibody targeting alpha4 integrin, has been approved for multiple sclerosis (MS) due to its higher efficacy and favorable safety profile compared to previous treatments.

The development of monoclonal antibodies for MS has progressed significantly, overcoming initial challenges, and they are now considered promising therapies, with ongoing research into new targets and existing antibodies for treating the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Getting specific: monoclonal antibodies in multiple sclerosis. Lutterotti, A., Martin, R.[2014]

Glatiramer acetate (GA) has been safely used for over 20 years in treating relapsing-remitting multiple sclerosis (MS), showing a 30% reduction in annual relapse rates and decreased brain lesion activity, with no new safety concerns reported.

GA's unique anti-inflammatory and neuroprotective mechanisms help slow brain atrophy and delay the onset of clinically definite MS, making early treatment more effective, while also being safe for use during pregnancy and in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis. Boster, AL., Ford, CC., Neudorfer, O., et al.[2022]

In a study of 13,489 patients receiving anti-TNFα therapy, only 35 cases of demyelination were identified, indicating that such events are uncommon, with an incidence rate of 19.7 per 100,000 patient-years.

The standardized incidence ratio (SIR) for demyelination in patients on anti-TNFα therapy was slightly elevated at 1.38 compared to the general UK population, but this increase was not significant in further analyses, suggesting that patients can be reassured about the safety of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demyelinating Events Following Initiation of Anti-TNFα Therapy in the British Society for Rheumatology Biologics Registry in Rheumatoid Arthritis. Taylor, TRP., Galloway, J., Davies, R., et al.[2021]

In a study of 228 multiple sclerosis patients treated with ocrelizumab, 91.2% of those with relapsing forms of MS achieved no evidence of disease activity (NEDA) after one year, indicating strong effectiveness in managing the disease.

The treatment was generally well-tolerated, with the most common side effects being infusion-related reactions and infections, particularly urinary tract infections, suggesting a favorable safety profile in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. Fernandez-Diaz, E., Perez-Vicente, JA., Villaverde-Gonzalez, R., et al.[2021]

Analysis of over 7000 pregnancies from Teva's global pharmacovigilance database indicates that exposure to branded glatiramer acetate (GA) during pregnancy does not increase the risk of congenital anomalies compared to the general population.

The findings suggest that branded GA has a favorable safety profile for pregnant women with multiple sclerosis, providing reassurance for its use during pregnancy without teratogenic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy Outcomes from the Branded Glatiramer Acetate Pregnancy Database. Sandberg-Wollheim, M., Neudorfer, O., Grinspan, A., et al.[2022]

In a real-world study of 886 multiple sclerosis patients on dimethyl fumarate (DMF) for an average of 39.5 months, the treatment showed good tolerability and safety, with 71.2% experiencing adverse events, primarily flushing.

Women were found to have a higher risk of certain adverse events, and patients with greater disability (higher EDSS scores) had an increased risk of discontinuing DMF, indicating the need for careful monitoring in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population. Sabin, J., Urtiaga, S., Pilo, B., et al.[2021]

In a study of 299 patients with multiple sclerosis treated with dimethyl fumarate (DMF), it was found that CD8+ T cells and CD56+ Natural Killer cells significantly decreased during treatment, indicating a notable impact on the immune system.

The CD4:CD8 T cell ratio showed the most significant changes in response to starting and stopping DMF, suggesting it could be a sensitive marker for monitoring immune changes in patients on this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of changes in lymphocyte levels in patients with multiple sclerosis during and after Tecfidera® treatment. Baeva, ME., Baev, PB., Nelson, J., et al.[2022]

A study using single-cell RNA sequencing on blood samples from patients with relapsing-remitting multiple sclerosis (RRMS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) revealed distinct immune cell signatures that can help differentiate between the two diseases.

RRMS was characterized by increased naive CD8+ T cells and cytotoxic memory-like NK cells, while MOGAD showed higher levels of inflammatory monocytes and cytotoxic CD8 effector T cells, indicating that these immune profiles could improve diagnostic accuracy and inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Cell Transcriptome Profiling Unravels Distinct Peripheral Blood Immune Cell Signatures of RRMS and MOG Antibody-Associated Disease. Liu, J., Yang, X., Pan, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04943289

NCT04943289 | Intrathecal Administration of DUOC-01 in ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9446943/

Abstract 15 Safety of DUOC-01, Intrathecal Cord Blood- ... Escalating DUOC doses are being tested for safety and exploration of potential efficacy in a phase Ia trial of adults with multiple sclerosis. Articles from ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1465324920300803

DUOC-01, a cord blood derived cell therapy product ... Previously, we showed that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the brain of immune-incompetent mice ...

4. marcuscenter.duke.edu marcuscenter.duke.edu/clinical-trials/current-trials

Current Trials | Duke Marcus Center for Cellular Cures The purpose of this open label Phase I study is to assess the safety and potential efficacy of DUOC-01 cells in adults with Primary Progressive Multiple ...

5. stemcellsjournals.onlinelibrary.wiley.com stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.12810

Hydrocortisone‐Treated DUOC‐01, a Cord Blood‐Derived ... Earlier, we demonstrated that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the brain of immune- ...

6. cells4life.com cells4life.com/us/2022/09/ms-clinical-trial/

New Phase in MS Stem Cell Clinical Trials A new Phase 1a open-label single-centre study is underway to assess the safety of administering DUOC-01 cells to adult patients with Primary ...

7. academic.oup.com academic.oup.com/stcltm/article/13/Supplement_1/S35/7738258

Umbilical Cord Blood Derived Macrophages, DUOC-01 ... In this study, we determined DUOC-01 alleviated EAE, at least in part by suppressing the activation of brain endothelial cells. This restored ...