Clinical trial NCT04387734: Effects of Ocrevus in Relapsing Multiple Sclerosis
Official title: Effects and Mechanisms of Ocrevus on Ambulatory Functions in People With Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Relapsing Multiple Sclerosis
Keywords: Mobility; Fall risk; Balance; Multiple sclerosis; T2LV
Lead sponsor: Georgia State University
Sponsor class: OTHER
Collaborators: name: Multiple Sclerosis Center of Atlanta
First posted: 2020-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test if people with relapsing multiple sclerosis (RMS) can improve ambulatory functions after one-year treatment with Ocrevus in comparison with other Disease Modifying Treatments (DMT). Sixty qualified individuals with RMS will be evenly assigned into two groups: Ocrevus and other DMT. Each group will receive the respective treatment following the FDA regulations over the one-year course. Their ambulatory functions will be assessed five times three months apart. In addition, they will receive brain MRI scans three times six months apart. Their ambulatory functions and MRI measurements will be compared between groups over time to fulfill the purposes of this study.


Eligibility criteria: Inclusion Criteria:

1. Ability to provide written, informed consent and to be compliant with the schedule of protocol assessments;
2. Ages 18-65 years old at screening;
3. Clinically confirmed active, relapsing forms of MS (RMS) based on the revised McDonald criteria;
4. Can walk at least 25 feet independently with or without assistive device at screening (or the Expanded Disability Status Scale between 1 and 6.5);
5. Can stand independently for at least 30 seconds;
6. Not pregnant at screening and throughout the study;
7. No other neurological conditions and recent musculoskeletal injuries;
8. Can read and understand English;
9. No significant cognitive impairment.

Exclusion Criteria:

1. History of other types of MS at screening such as, primary-progressive MS);
2. Inability to complete an MRI (contraindications for MRI include but are not limited to claustrophobia, body mass greater than 140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks before the time of the intended MRI, etc);
3. Patients with an active hepatitis B virus (HBV) infection;
4. Have a life-threatening allergic reaction to ocrelizumab or any of its ingredients in the past;
5. Hypersensitive to any of the ingredients of ocrelizumab;
6. Do not understand English.

   Exclusions related to general health
7. Pregnancy or lactation;
8. Have any other known neurological diseases which may mimic MS including but not limited to: Neuromyelitis optica, Lyme disease, untreated vitamin B12 deficiency, neurosarcoidosis, and cerebrovascular disorders;
9. Suffering from coexisting psychiatric disorders, neurological disorders, or severe medical illness;
10. Current severe depression and/or suicidal ideation;
11. Significant cognitive impairment (Montreal Cognitive Assessment score \< 24);
12. New onset, unstable orthopedic comorbid diagnoses (within 3 months and uncontrolled);
13. History or currently active primary or secondary immunodeficiency;
14. Receipt of a live vaccine within 6 weeks prior to baseline;
15. Skin is allergic to transparent double-side tapes;
16. Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study;
17. History or currently active primary or secondary immunodeficiency;
18. Lack of peripheral venous access;
19. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
20. Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study;
21. Congestive heart failure (NYHA III or IV functional severity);
22. Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds;
23. Infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit;
24. History or known presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis, tuberculosis);
25. History of progressive multifocal leukoencephalopathy (PML);
26. History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised with documented, clear margins;
27. History of alcohol or drug abuse within 24 weeks prior to baseline;
28. History or laboratory evidence of coagulation disorders;

    Exclusions related to medications
29. Receipt of a live vaccine within 6 weeks prior to baseline;
30. Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer);
31. Contraindications to or intolerance of oral or intravenous corticosteroids, including methylprednisolone administered intravenous, according to the country label, including:

    1. Psychosis not yet controlled by a treatment;
    2. Hypersensitivity to any of the constituents;
32. Treatment with dalfamipridine (Ampyra®) unless on stable dose for ≥ 30 days prior to screening. Patients should remain on stable doses throughout the 52-week treatment period;
33. Previous treatment with B-cell targeted therapies (i.e. rituximab, ocrelizumab, atacicept, belimumab or ofatumumab);
34. Systemic corticosteroid therapy within 4 weeks prior to screening;
35. Any previous treatment with alemtuzumab (Campath), anti-CD4, cladribine, mitoxantrone, daclizumab, BG12, teriflunomide, laquinimod, total body irradiation or bone marrow transplantation;
36. Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil (MMF), cyclosporine, methotrexate, or natalizumab within 24 months prior to screening;
37. Treatment with intravenous immunoglobulin within 12 weeks prior to baseline.

    Exclusions related to motor function
38. Cannot walk at least 25 feet and stand at least 30 seconds independently;
39. Weak or blind vision may impair their ability of walking;

    Exclusions related to musculoskeletal, cardiovascular, and orthopedic condition
40. Broken bones as an adult in the past year;
41. Have received neurological treatment, such as Botox, in the past six months;
42. Heart attack, angioplasty, or coronary artery bypass graft in the past six months;
43. Congestive heart failure (NYHA III or IV functional severity);
44. Surgery on back, hip, shoulder, or total joint replacement of hip or knee joint less than two years ago;
45. Respiratory conditions (lung cancer, bronchitis, emphysema, asthma, shortness of breath) not under regular medical care or the patient is medically unstable.

    Exclusions related to laboratory findings
46. Positive serum β hCG measured at screening;
47. Positive screening tests for hepatitis B (hepatitis B surface antigen \[HBsAg\] positive, or positive hepatitis B core antibody \[total HBcAb\] confirmed by a positive viral deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\]) or hepatitis C (HepCAb);
48. Positive rapid plasma reagin (RPR);
49. CD4 count \< 300/μL;
50. AST/SGOT or ALT/SGPT ≥ 2.0 Upper Limit of Normal (ULN);
51. Platelet count \<100,000/μL (\<100 x 109/L);
52. Levels of serum IgG \<5.65 g/L;
53. Levels of serum IgM \< 0.55 g/L;
54. Total neutrophil count \<1.5 x 103/μL.

Primary outcomes:
measure: Dynamic Gait Stability
timeFrame: 12 months
Secondary outcomes:
measure: Gait speed
timeFrame: 12 months
measure: Step length
timeFrame: 12 months
measure: Step width
timeFrame: 12 months
measure: Step time
timeFrame: 12 months
measure: Cadence
timeFrame: 12 months
measure: Stability index
timeFrame: 12 months
measure: Swing index
timeFrame: 12 months
measure: Lower limb muscle strength
timeFrame: 12 months
measure: Lower limb muscle activity
timeFrame: 12 months
measure: Multiple Sclerosis Functional Composite
timeFrame: 12 months
measure: Expanded Disability Status Scale
timeFrame: 12 months
measure: Total cerebral T2 lesion volume
timeFrame: 12 months
measure: Prospective falls
timeFrame: 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Georgia State University
state: Georgia
city: Atlanta
country: United States
facility: Multiple Sclerosis Center of Atlanta
state: Georgia
Study officials:
affiliation: Georgia State University
name: Feng Yang, PhD
role: PRINCIPAL_INVESTIGATOR
References: