Intrathecal Administration of DUOC-01 in Adults With Primary Progressive Multiple Sclerosis

Phase

Condition

Multiple Sclerosis

Neurologic Disorders

Memory Loss

Treatment

DUOC-01

Clinical Study ID

NCT04943289

Pro00107012

Ages 18-65
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Male and female subjects must be 18-65 years of age
Diagnosis of primary progressive MS according to 2017 revised McDonald criteria (26)
EDSS score at screening 3.0-6.5 that was not acquired within the last 6 months
Stable disease state as evidenced by no significant change in EDSS (1 point or more)in the last 3 months
Patients must have a suitably matched, banked UCB per section 5.3
Able to complete a written informed consent prior to any study assessments
Patients of childbearing potential must practice effective contraception during thestudy, and be willing to continue contraception for at least 6 months after DUOC-01dosing so that, in the opinion of the Investigator, they will not become pregnantduring the course of the study.
Patient is a good candidate for the trial, in the opinion of the Investigators
Subjects on disease-modifying therapies upon entering the study must continue onthese therapies as a concomitant treatment throughout the course of the study tominimize additional variables. However, changes in these disease-modifying therapiescan occur at the clinician's discretion, if there are clinical reasons to do so,which would be documented.

Exclusion

Exclusion Criteria:

1. Prior organ, tissue, or stem cell transplant or cell therapy within 3 years ofstudy entry 2. Diagnosis of a progressive neurological disorder other than MS 3.Active, chronic disease of the immune system other than MS 4. Any medical conditionthat the investigator deems as unsuitable with therapy 5. Inability to have an MRIbrain scan, or lumbar puncture (i.e., claustrophobia, allergy to contrast, bleedingdisorder, or on anticoagulation) 6. Intractable seizures 7. Chronic aspiration 8.Bleeding disorder 9. Evidence of HIV infection or HIV positive serology 10.Uncontrolled bacterial, viral, or fungal infection within 2 weeks of DUOC-01administration, as defined by progression while on appropriate treatment 11. Historyof malignancy of any organ system within the past two years with the exception ofbasal cell carcinoma or squamous cell carcinoma of the skin that has been excisedwith clear margins. 12. Requirement of ventilatory support 13. Pregnant orbreastfeeding or intention to become pregnant during the study 14. Active concurrentmalignancy, or receiving concurrent radiotherapy, immunosuppressive medications forconditions other than MS, or cytotoxic chemotherapy 15. Patients with SuicidalIdeation in the past 6 months per screening on C-SSRS; patients with SuicidalBehavior in the past 2 years, except for Non-suicidal self-injurious behavior 16.Abnormal lab values:
Total bilirubin>2.0 mg/dl unless due to Gilbert's syndrome
AST or ALT > 5 times the ULN
WBC <2.0x 103/μL
ALC <0.5 x 103/ μL
Serum creatinine >2x ULN
eGFR <60 mg/mmol
CD4 count <200 cells/mm3

Study Design

DUOC-01

January 24, 2021

September 30, 2025

Study Description

This study is a prospective phase 1a open-label, single center trial. It is designed to assess the safety of administration of escalating doses of DUOC-01 intrathecally to adults with PPMS. DUOC-01 is a population of cells expanded from donated human umbilical cord blood mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. Based on pre-clinical rodent models, this cell product is considered a candidate for the treatment of injury-induced Central Nervous System (CNS) demyelination and modulation of neuroinflammation.

Approximately 20 participants will be enrolled. DUOC-01 will be infused into the cerebrospinal fluid (intrathecal infusion). The first 3 subjects will receive a single dose of 10 million cells (cohort 1). The next 3 subjects will receive a single intrathecal dose of >10 to 25 million cells (cohort 2), if manufacturing of this yield is reliable. The final 14 patients will receive a single intrathecal dose of >25 to 50 million cells (cohort 3), if manufacturing of this yield is reliable. Subjects will be followed for 12 months post administration.

Participants will be identified and screened for eligibility for the study. HLA typing will be performed on the participant, and once results become available, several >4/6 matched cord blood units (CBUs) will be selected from the Carolinas Cord Blood Bank (CCBB), an FDA licensed public cord blood bank at Duke University in Durham, NC. Cord blood units will have complete donor screening and testing per banking regulations.

The frozen CBU will be transferred to the GMP manufacturing facility at Duke University Medical Center per standard practice. Production, testing and release of DUOC-01 will take 19-21 days. Within 14 days prior to planned administration, subjects will receive a baseline brain MRI and be re-screened on MS assessments. Subjects will not be infused with DUOC-01 cells if they no longer meet inclusion criteria or if no qualifying DUOC-01 cells are available. If there is a failure of DUOC-01 manufacturing, a second cord blood unit, if available, will be utilized for repeat manufacturing.

DUOC-01 administration will occur by a trained clinician. A lumbar puncture (insertion of a needle into the lower back, into the cerebrospinal spinal fluid (CSF)) will be performed and baseline CSF samples will be obtained. The DUOC-01 product will be injected into the CSF (intrathecally) and appropriate monitoring will be performed.

Post administration, all subjects will remain in the hospital for 24-hour observation. At 2 weeks post administration subjects will participate in a virtual visit to evaluate for adverse events. Subjects will receive follow up visits with functional evaluation, biomarker sampling and brain MRI at 3, 6 and 12 months.

Connect with a study center

Duke University Medical Center
Durham, North Carolina 27705
United States
Site Not Available
Duke University Medical Center
Durham 4464368, North Carolina 4482348 27705
United States
Site Not Available

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