Autoimmune Diseases, Demyelinating Diseases, Immune System Diseases, Multiple Sclerosis, Nervous System Diseases, Pathologic Processes, Primary Progressive Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis
Conditions
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.
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.
Interventions
DRUGOcrelizumab
Ocrelizumab is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug candidate. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds
Sponsors
Genentech, Inc.
University of South Florida
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stabilization of Scores Using 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 is designed to assess the capabilities and limitations of upper limb function and 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. Each task is 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
| Measure | Time frame | Description |
|---|---|---|
| Stabilization of 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 in performing activities of daily living using the upper extremities including household and work activities, hobbies, lifting a bag of groceries, washing their scalp, pushing up on their hands, driving etc. |
| Stabilization of 9-Hole Peg Test Scores | 24 months | The 9HPT is an objective measure of finger dexterity and upper extremity function, which is a widely used measure across most clinical trials in multiple sclerosis populations. The test involves the participant picking up and placing pegs one at time in the 9 holes and removing the pegs from their respective holes as quickly as possible. The participant completes the tasks twice on using their dominant hand, then twice on their non-dominant hand. Higher scores indicate a worse outcome. |
Countries
United States
Participant flow
Recruitment details
Enrollment occured July 2018 through September 2020 at a university medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Clinical Stabilization (Defined as no Significant Change (≤20%) From Baseline Measure of upper extremity function over 24 months after initiation of Ocrevus™ | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Clinical Stabilization (Defined as no Significant Change (≤20%) From Baseline | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 3 Participants | — |
| Age, Categorical Between 18 and 65 years | 15 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 12 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 18 |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
Stabilization of Scores Using 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
The TEMPA is designed to assess the capabilities and limitations of upper limb function and 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. Each task is 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).
Time frame: 24 months
Population: cohort of patients with Multiple Sclerosis from University of South Florida Multiple Sclerosis Center.~Individuals, ages 18-70, with relapsing or progressive forms of MS and UE impairment that satisfied the approved indication for ocrelizumab and received ocrelizumab treatment commercially were assessed quarterly and semi-annually over 24 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| <20% Change of Clinical Stabalization From Baseline | Stabilization of Scores Using 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 | 12 Participants |
Secondary
Stabilization of 9-Hole Peg Test Scores
The 9HPT is an objective measure of finger dexterity and upper extremity function, which is a widely used measure across most clinical trials in multiple sclerosis populations. The test involves the participant picking up and placing pegs one at time in the 9 holes and removing the pegs from their respective holes as quickly as possible. The participant completes the tasks twice on using their dominant hand, then twice on their non-dominant hand. Higher scores indicate a worse outcome.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| <20% Change of Clinical Stabalization From Baseline | Stabilization of 9-Hole Peg Test Scores | 11 Participants |
Secondary
Stabilization of the Upper Extremity Functional Index (UEFI)
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 in performing activities of daily living using the upper extremities including household and work activities, hobbies, lifting a bag of groceries, washing their scalp, pushing up on their hands, driving etc.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| <20% Change of Clinical Stabalization From Baseline | Stabilization of the Upper Extremity Functional Index (UEFI) | 9 Participants |