Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus

Sponsor

University of South Florida (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03562975

Collaborator

Genentech, Inc. (Industry)

Enrollment

Location

52.3

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators are measuring the effectiveness of Ocrevus™ in helping patients with hand or arm weakness, especially if posed by a more advanced MS patient than those included in the clinical trials.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Pathologic Processes Demyelinating Diseases Nervous System Diseases Autoimmune Diseases Immune System Diseases Primary Progressive Multiple Sclerosis Relapsing Remitting Multiple Sclerosis	Drug: Ocrelizumab

Detailed Description

Ocrevus™ is the first FDA approved disease-modifying treatment for primary progressive multiple sclerosis (PPMS) as well as relapsing MS. In the clinical trials considered by the FDA (OPERA I/II, ORATORIO), the highest Expanded Disability Status Scale (EDSS) included in the participants was 5.5 (OPERA I/II) and 6.5 (ORATORIO). The EDSS score is heavily weighted on walking ability and is not a useful measurement for UE function. The primary endpoint in the primary progressive MS trial with Ocrevus™ was EDSS and in the relapsing MS studies, EDSS was used as a secondary endpoint. The Multiple Sclerosis Functional Composite (MSFC) score (Z score), a composite of quantitative measure of walking speed, upper limb coordinated movement (9 Hole Peg Test/9HPT) and cognitive function, was obtained as a secondary clinical measure with scores being favorably higher in patients treated with Ocrevus™ (OPERA I/II).The z score, however, is not very useful in delineating which of the three clinical functions was maintained or showed less progression given that three domains are included in the score. Data presented recently from the Oratorio trial analyzed the intention to treat population of PPMS patients and the subgroups of patients with upper extremity functional impairment using the 9HPT; results demonstrated reduction in risk of clinical progression in upper extremity disability in patients treated with Ocrevus compared to placebo. There was improvement in the change from baseline to week 120 in 9HPT time in treated patients. Abnormal baseline 9HPT was defined as >25 seconds and upper extremities were defined as "better hand" and "worse hand", each individually tested, with clinical progression determined at 12 and 24 weeks in 3 sub-categories of progression: lengthened time of 9HPT >15%, >20% and 25%.

In this study, investigators aim to not only replicate the results in the Oratorio trial with upper extremity dysfunction, but also widen the spectrum of patients that may benefit (given an expanded MS population of patients, not exclusive to PPMS and widen the It is anticipated that by using a test that better emulates activities of daily life performed with the upper extremity, such as the TEMPA (Test d'Evaluation de la performance des membres Superieurs e Personnes Agees ) more real life application of the benefits of receiving treatment with Ocrevus will be obtained, and it is anticipated that patients can maintain the function they have or potentially improve function.

Study Design

Study Type:

Observational

Actual Enrollment :

18 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

A Single-center Prospective Measurement of Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus™

Actual Study Start Date :

Jul 23, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Outcome Measures

Primary Outcome Measures

The Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées (TEMPA) -Translasted in English to mean "Performance Evaluation Test for the Elderly" [24 months]
The TEMPA consists of 9 tasks that mimic tasks of daily living that include picking up a jar, taking a spoonful of coffee from a jar, pouring water from a pitcher, handling coins, writing on an envelope and opening a pill container, tying a scarf around one's neck, shuffle and deal playing cards, and picking up and moving small objects. The tasks are assessed by a rater by measuring speed of execution (seconds) and by functional rating of the subject's independence in performing them using an ordinal scale of 0 (completed without difficulty) to -3 (could not complete the task).

Secondary Outcome Measures

The Upper Extremity Functional Index (UEFI) [24 months]
The Upper Extremity Functional Index (UEFI) is a self-administered questionnaire which measures disability in patients with upper extremity conditions on a 5-point Likert scale. Scores range from 0 to 60 with lower scores indicating more functional difficulty.
9-Hole Peg Test [24 months]
The 9HPT is an objective measure of manual dexterity, which is incorporated into the MSFC, is a widely used measure across most clinical trials in multiple sclerosis populations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI])
Aged 18-70 at the time of informed consent
Must have a relapsing or progressive form of MS
Plan to begin Ocrevus™ treatment but have not actually had first treatment yet
Male subjects and female subjects of child-bearing potential (including female subjects who are not post-menopausal for at least 1 year) must be willing to practice effective contraception (as defined by the investigator) during the study and be willing and able to continue contraception for 6 months after their last dose of study treatment
EDSS 4.0-8.0
UE weakness in at least one limb, defined as grade 4/5 in ≥ 2 muscles per limb
Muscle weakness must be primarily related to MS
Joint range of motion must be within functional limits
Patient must be able to perform 9HPT and TEMPA tests with at least one limb

Exclusion Criteria:

Prior treatment with Ocrevus™ (Cannot already be on Ocrevus prior to joining the study)
Severe weakness in bilateral upper limbs causing complete loss of function
History of severe allergic or anaphylactic reactions or known drug hypersensitivity
Female subjects considering becoming pregnant while in the study
Female subjects who are currently pregnant or breast-feeding
Unwillingness or inability to comply with the requirements of the protocol including the presence of any conditional (physical, mental or social) that is likely to affect the subject's ability to comply with the protocol.
Active Hepatitis B virus infections
Severe tremor/ataxia of the UE as defined by an EDSS with Cerebellar Functional System score of 3 or more due to upper extremity score (moderate tremor or clumsy movements interfere with function in all spheres)