Inclusion Criteria:

1. Demonstrate Expanded Disability Status Scale (EDSS) scores between 3 to 6.5 at screening. 2. Documented EDSS progression in the 2 years prior to screening of 1 point or greater for patients with an EDSS score less than 6 at baseline, and greater than or equal to 0.5 for patients with an EDSS score greater than or equal to 6.0 at baseline *. * If documented EDSS scores are not available, a written summary of the clinical evidence of disability progression over the last 2 years, and retrospective assessment of EDSS score from data in the medical records, must be submitted for review by the principal investigators. 3. Documented initial onset characterized by a relapsing-remitting course as described in the Diagnostic Criteria. 4. Age ≥ 18 ≤ 75 years. 5. Weight > 40 kg. 6. Hematocrit ≥ 28 % (with or without transfusion support). 7. Platelet count > 100,000 per μL (with or without transfusion support). 8. Willingness to use at least 1 reliable method of birth control (e.g., abstinence, oral contraceptives, intrauterine devices, barrier method with spermicide, or surgical sterilization) throughout the study for all men and women of childbearing potential. 9. Willingness to participate in all PHOMS Study tests, visits, and procedures (including the ECP), as outlined in the informed consent. 10. Patients must have adequate peripheral venous access to initiate ECP therapy, and central line insertion shall be required. 11. The patient agrees to participate in the trial and signs the PHOMS Study informed consent form.

Exclusion Criteria:

1. Absolute medical contraindication to receive ECP. 2. Laboratory evidence of any of the following:

• - White blood cells (WBC) < 2,000 cells per uL.

• - Serum transaminase levels > x 2 UNL.

• - Creatinine Clearance < 60 mL/min.

3. Concurrent diagnosis of a neurological condition that would interfere with the assessment of MS, or an autoimmune disease or inflammatory condition that is chronically treated with immunosuppressive agents. 4. Evidence of known infection with human immunodeficiency virus (HIV) or active (not including latent) Hepatitis B. 5. Uncontrolled infection requiring treatment at study entry. 6. Hypersensitivity or allergy to psoralen (methoxalen). 7. Hypersensitivity or allergy to both heparin and citrate products (If hypersensitive or allergic to only one of these products, exclusion does not apply). 8. Inability to tolerate fluid changes associated with ECP (e.g., inadequate renal, hepatic, pulmonary and cardiac function leading to enable patient to tolerate extracorporeal volume shifts associated with ECP). 9. Presence of aphakia or photosensitive disease (systemic lupus erythematosus, porphyrias, etc.). 10. Women who are pregnant and/or lactating. 11. Use of any investigational drug/treatment at the time of enrollment or within the previous 60 days, or five elimination half-lives, or until the expected pharmodynamic effect has returned to baseline, whichever is longer. 12. Treatment with any of the medications or procedures listed below:

• - Natalizumab, or rituximab within 3 months prior to randomization.

• - Cyclophosphamide within 1 year prior to randomization.

• - Mitoxantrone, ofatumumab, ocrelizumab, cladribine, or daclizumab within 1 years prior to randomization.

• - Intravenous immunoglobulin within 3 months prior to randomization.

• - Plasmapheresis within 3 months prior to randomization.

13. Inability to undergo MRI scans. 14. Contraindication to gadolinium due to past allergic, hypersensitive, or adverse reaction or impaired renal function. Patients receiving a steroid prep prior to gadolinium administration due to history of hypersensitivity or allergy to other agents or due to prior mild reaction to gadolinium will not be excluded from the study. 15. Poor venous access. 16. Previous history of skin cancer, leukemia / lymphoma / myeloma, or bone marrow transplant. 17. Patients taking Coumadin who are unable to switch from oral anticoagulants to enoxaparin. 18. Heparin-induced thrombocytopenia. 19. Poor cardiac function. 20. Severe hypotension. 21. Any other disease or condition which, in the opinion of the investigator, could interfere with participation according to the PHOMS Study Protocol, or with the ability of the patients to cooperate and comply with study procedures. 22. Inability to provide informed consent.

PHOMS patients will be randomly allocated (2:1) in a parallel assignment involving two groups of participants: Group A (Experimental group, n = 30): ECP plus Multiple Sclerosis (MS) standard of care, or Group B (Control group, n = 15) receiving MS standard of care alone. The PHOMS Study standard of care is defined by Disease-modifying Therapy (DMT) recommended by the American Academy of Neurology (AAN). The Study will be conducted within Abu Dhabi Stem Cells Center (ADSCC) and Yas Clinic Khalifa City (YCKC) Hospital, including patient assessment and inclusion, randomization, ECP procedures (Group A), and follow-up consultations, according to the approved Protocol and Good Clinical Practices (GCPs) principles. The primary objective is the safety profile assessment of the investigational intervention (ECP), to be assessed by procedure tolerability, the incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0), and the World Health Organization

• - Uppsala Monitoring Center (WHO-UMC) causality assessment system.

The ECP preliminary efficacy assessment, as another primary objective, will be assessed by the proportion of subjects with no evidence of disease progression at 1 year; while the secondary objective is the assessment of the immune response profile in MS patients. All subjects will undergo longitudinal Expanded Disability Status Scale (EDSS), 25-foot walk ambulation test, 9-hole peg test, and 36-Item Short Form Survey (SF-36) testing at baseline and every 3 months through 1 year. Blood will be collected for immunological testing at baseline, months 3, 6, 9, and 12; and subjects will also undergo neuroimaging with brain Magnetic Resonance Imaging (MRI) at baseline, and months 6 and 12 following initiation of treatment, while Chest X-Ray, electrocardiogram (ECG), and echocardiogram can be required at the discretion of the Investigator. The trial is approved by the institutional Research Ethics Committees (RECs), and written informed consent will be obtained from all patients. PHOMS Study will be conducted following the principles of the Declaration of Helsinki and the International Conference on Harmonization (ICH) GCP Guidelines. The authors are responsible for designing the trial and for compiling and analyzing the data.

Arms

Experimental: Group A (ECP + SoC Group)

Extracorporeal photopheresis (ECP) plus Multiple Sclerosis (MS) standard of care

Active Comparator: Group B (SoC Group)

MS standard of care alone (SoC, defined by Disease-modifying Therapy -DMT, recommended by the American Academy of Neurology -AAN

Interventions

Combination Product: - Extracorporeal Photopheresis

ECP procedures will be performed using a Therakos Cellex integrated, closed photopheresis system (Therakos, Inc., a Mallinckrodt Pharmaceuticals Company). ECP will administered according to the following schedule (Group A): Weeks 1-8: Twice per week (16 sessions). Weeks 9-16: Once per week (8 sessions). Weeks 17-24: Once every 2 weeks (4 sessions). Total: 28 sessions (within 24 weeks).

Combination Product: - MS standard of care

Disease-modifying Therapy -DMT, recommended by the American Academy of Neurology -AAN