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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
| Novartis Institutes for BioMedical Research | OTHER |
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In this study, lymph fluid will be collected by cannulation of the thoracic duct, a minimally invasive procedure performed by interventional radiologists. Single time point and serial collection through an indwelling cannula will allow for comparisons between immune cells in the periphery and deep lymphatic system in MS and healthy controls and in MS, changes in responses to a FDA approved therapy ofatumumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 'In-and-out' catheterization | Other | Safety and immune-cell profile of lymphatic fluid in MS patients with a single time-point sampling of lymphatic fluids and peripheral blood compared to healthy controls. Two healthy controls and six patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to the 'In-and-out' catheter procedure. MS participants can also consent to OMB treatment with 2-year follow-up. |
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| "Indwelling" catheterization | Other | immune-biology in people with MS before and during/after OMB treatment within thoracic duct and peripheral blood via indwelling catheter and multiple time-point sampling compared to healthy controls (without drug treatment). Twelve patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to treatment with OMB and to the indwelling catheter procedure with serial sampling and up to four healthy controls (no drug treatment) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| thoracic duct cannulation | Procedure | Contrast is injected into lymph nodes until lymphatics visualized at about level of L3 lumbar spine. After target lymphatic vessel is identified, needle is passed transabdominally into the vessel. Guidewire is advanced through the needle into the lymph vessel & advanced into thoracic duct. Microcatheter is then advanced into thoracic duct over the wire. IN & OUT-up to 100mL collected via catheter over 30-min at 2 levels within thoracic duct, then catheter removed. INDWELLING-As described above, then guidewire placed through original catheter & advanced into subclavian vein. Vascular sheath is placed into vein in the upper arm under ultrasound/fluoroscopy guidance. Wire in the subclavian vein then snared through venous access sheath & pulled out. Catheter then threaded & advanced over the wire until tip is in thoracic duct. Catheter from thoracic duct removed, leaving catheter extending from arm into thoracic duct. Catheter left in place up to 21 days for sampling. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability | Quantified as percent of the study population experiencing serious adverse event from in-and-out catherization procedure and from "indwelling" catheterization procedure | up to 21 days |
| B Cells | Change in proportion of flow cytometry defined naïve (CD27-) and memory (CD27+) B cells in thoracic duct of patients with MS prior to and following anti-CD20 therapy with Ofatumumab | up to 21 days |
| Measure | Description | Time Frame |
|---|---|---|
| Immune cell profiles (MS and healthy controls) | Comparison of immune cell profiles determined by flow cytometry of lymphatic fluid and blood between MS and healthy controls | up to 21 days |
| Immune cell profiles (ofatumumab) |
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Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
For participants with MS following additional criteria need to be met:
Exclusion Criteria:
1. Participants suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator.
2. Participants with primary progressive MS (Polman C et al., 2011) 3. Participants meeting criteria for neuromyelitis optica (Wingerchuck D et al., 2015) 4. Participants with disease duration of more than 10 years 5. Participants who are pregnant or nursing (lactating) 6. Participants with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency) 7. Participants with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS) 8. Participants with neurological symptoms consistent with PML or confirmed PML 9. Participants at risk of developing or having reactivation of syphilis or tuberculosis 10. History of cardiovascular disease or uncontrolled hypertension 11. History of diabetes mellitus 12. History of cancer (other than localized skin cancer) in the previous 5 years 13. Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to first study drug administration 14. Immunization with non-live vaccines within 2 weeks of the study procedure 15. Participants at risk of developing or having reactivation of hepatitis: Positive results at Screening for serological markers for hepatitis (H) B and C indicating acute or chronic infection:
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| Name | Affiliation | Role |
|---|---|---|
| Amit Bar-Or, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 18, 2022 | Jun 13, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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Comparison of immune cell profiles determined by flow cytometry of lymphatic fluid and blood of MS patients prior to and following treatment with the anti-CD20 Ofatumumab
| up to 21 days |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |