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

NCT ID: NCT03562975

Last Updated: 2024-12-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

18 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-07-23

Study Completion Date

2023-01-11

Brief Summary

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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

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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.

Conditions

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Multiple Sclerosis Pathologic Processes Demyelinating Diseases Nervous System Diseases Autoimmune Diseases Immune System Diseases Primary Progressive Multiple Sclerosis Relapsing Remitting Multiple Sclerosis

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Interventions

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Ocrelizumab

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

Intervention Type DRUG

Other Intervention Names

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Ocrevus

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

University of South Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janice Y Maldonado, MD

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

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Carol and Frank Morsani Center for Advanced Healthcare

Tampa, Florida, United States

Site Status

Countries

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United States

References

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Lamers I, Feys P. Assessing upper limb function in multiple sclerosis. Mult Scler. 2014 Jun;20(7):775-84. doi: 10.1177/1352458514525677. Epub 2014 Mar 24.

Reference Type BACKGROUND
PMID: 24664300 (View on PubMed)

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.

Reference Type BACKGROUND
PMID: 6685237 (View on PubMed)

Ontaneda D, Fox RJ, Chataway J. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives. Lancet Neurol. 2015 Feb;14(2):208-23. doi: 10.1016/S1474-4422(14)70264-9.

Reference Type BACKGROUND
PMID: 25772899 (View on PubMed)

Schwid SR, Goodman AD, McDermott MP, Bever CF, Cook SD. Quantitative functional measures in MS: what is a reliable change? Neurology. 2002 Apr 23;58(8):1294-6. doi: 10.1212/wnl.58.8.1294.

Reference Type BACKGROUND
PMID: 11971105 (View on PubMed)

Hamilton GF, McDonald C, Chenier TC. Measurement of grip strength: validity and reliability of the sphygmomanometer and jamar grip dynamometer. J Orthop Sports Phys Ther. 1992;16(5):215-9. doi: 10.2519/jospt.1992.16.5.215.

Reference Type BACKGROUND
PMID: 18796752 (View on PubMed)

Benedict RH, Holtzer R, Motl RW, Foley FW, Kaur S, Hojnacki D, Weinstock-Guttman B. Upper and lower extremity motor function and cognitive impairment in multiple sclerosis. J Int Neuropsychol Soc. 2011 Jul;17(4):643-53. doi: 10.1017/S1355617711000403.

Reference Type BACKGROUND
PMID: 21486517 (View on PubMed)

Stratford P, Binkley J, Stratford D. Development and initial validation of the upper extremity functional index. Physiotherapy Canada 2001;53(4):259-67.

Reference Type BACKGROUND

Ropper AH, Samuels M.A. Principals of Neurology. 9th edition. New York: McGraw-Hill, 2009.

Reference Type BACKGROUND

Genentech. Ocrevus™: Highlights of prescribing information. 2017.

Reference Type BACKGROUND

Goodin DS. Multiple Sclerosis and Related Disorders. Amsterdam, The Netherlands: Elsevier, 2014.

Reference Type BACKGROUND

Fox, EJ, Markowitz, C, Montalban, X, et al. Effect of Ocrelizumab on Upper Extremity Function in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Study. Presented at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Meeting; 25-28 October 2017; Paris, France.

Reference Type BACKGROUND

Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.

Reference Type RESULT
PMID: 28002688 (View on PubMed)

Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

Reference Type RESULT
PMID: 28002679 (View on PubMed)

Cohen JA, Cutter GR, Fischer JS, Goodman AD, Heidenreich FR, Jak AJ, Kniker JE, Kooijmans MF, Lull JM, Sandrock AW, Simon JH, Simonian NA, Whitaker JN. Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial. Arch Neurol. 2001 Jun;58(6):961-7. doi: 10.1001/archneur.58.6.961.

Reference Type RESULT
PMID: 11405811 (View on PubMed)

Lamers I, Kelchtermans S, Baert I, Feys P. Upper limb assessment in multiple sclerosis: a systematic review of outcome measures and their psychometric properties. Arch Phys Med Rehabil. 2014 Jun;95(6):1184-200. doi: 10.1016/j.apmr.2014.02.023. Epub 2014 Mar 13.

Reference Type RESULT
PMID: 24631802 (View on PubMed)

Feys P, Duportail M, Kos D, Van Asch P, Ketelaer P. Validity of the TEMPA for the measurement of upper limb function in multiple sclerosis. Clin Rehabil. 2002 Mar;16(2):166-73. doi: 10.1191/0269215502cr471oa.

Reference Type RESULT
PMID: 11911515 (View on PubMed)

Gijbels D, Lamers I, Kerkhofs L, Alders G, Knippenberg E, Feys P. The Armeo Spring as training tool to improve upper limb functionality in multiple sclerosis: a pilot study. J Neuroeng Rehabil. 2011 Jan 24;8:5. doi: 10.1186/1743-0003-8-5.

Reference Type RESULT
PMID: 21261965 (View on PubMed)

Chesworth BM, Hamilton CB, Walton DM, Benoit M, Blake TA, Bredy H, Burns C, Chan L, Frey E, Gillies G, Gravelle T, Ho R, Holmes R, Lavallee RL, MacKinnon M, Merchant AJ, Sherman T, Spears K, Yardley D. Reliability and validity of two versions of the upper extremity functional index. Physiother Can. 2014 Summer;66(3):243-53. doi: 10.3138/ptc.2013-45.

Reference Type RESULT
PMID: 25125777 (View on PubMed)

Yozbatiran N, Baskurt F, Baskurt Z, Ozakbas S, Idiman E. Motor assessment of upper extremity function and its relation with fatigue, cognitive function and quality of life in multiple sclerosis patients. J Neurol Sci. 2006 Jul 15;246(1-2):117-22. doi: 10.1016/j.jns.2006.02.018. Epub 2006 May 5.

Reference Type RESULT
PMID: 16678208 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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OCRE-UP

Identifier Type: -

Identifier Source: org_study_id