Active, not recruiting
Phase 3
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)
Condition(s) studied
Multiple Sclerosis
Investigational drug(s) / intervention(s)
OcrelizumabOcrelizumabAntihistamineMethylprednisolone
Ocrelizumab: The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight \<75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W.
During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)
Ocrelizumab: Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg, IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.
Antihistamine: Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.
Methylprednisolone: Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.
Study summary
This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.
Eligibility
Inclusion Criteria:
* Diagnosis of PPMS
* EDSS score at screening and baseline, from 3 to 6.5 inclusive
* Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
* Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
* Score of ≥ to 2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
* Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS
* Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
* Participants must be neurologically stable for at least 30 days prior to randomization and baseline
* Disease duration from the onset of MS symptoms; if EDSS score at screening is ≤ 5, disease duration must be less than 10 years; If EDSS score at screening is \> 5, disease duration must be less than 15 years
* Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands
* Females of childbearing potential: agreement to remain abstinent or use adequate contraceptive methods
* Female participants, without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile
Exclusion Criteria:
* History of relapsing remitting or secondary progressive MS at screening
* Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening
* History of confirmed or suspected progressive multifocal leukoencephalopathy
* History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
* Immunocompromised state
* Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
* Inability to complete an MRI or contraindication to gadolinium administration
* Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)
* Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* Significant, uncontrolled disease that may preclude participant from participating in the study
* History of or currently active primary or secondary, non-drug-related, immunodeficiency
* Pregnant or breastfeeding or intending to become pregnant
* Lack of peripheral venous access
* History of alcohol or other drug abuse within 12 months prior to screening
* Treatment with any investigational agent or treatment with any experimental procedure for MS
* Previous use of anti-cluster of differentiation 20 (CD20s) (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy
* Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
* Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
* Previous treatment with natalizumab within 4.5 months of baseline
* Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
* Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
* Any previous history of transplantation or anti-rejection therapy
* Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
* Systemic corticosteroid therapy within 4 weeks prior to screening
* Positive screening tests for active, latent, or inadequately treated hepatitis B
* Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
* Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above
Primary outcome measure(s)
- Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) — Up to approximately 4.5 years
Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of the 3 criteria: 1) CDP=12-week confirmed increase (CI) from baseline (FB) in expanded disability status scale (EDSS) score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of \>5.5 OR 2) 12-week CI of ≥20% FB in Timed 25-foot Walk Test (T25FWT) score OR 3)12-week CI of ≥ 20% FB in 9-hole Peg Test (9-HPT) score. EDSS = disability scale that ranges in 0.5-point steps from 0 \[normal\]-10.0 \[death\]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.
Trial sites (147)
| Facility | City | Region | Status |
| Alabama Neurology Associates |
Homewood |
Alabama |
|
| 21st Century Neurology |
Phoenix |
Arizona |
|
| University of California Irvine |
Irvine |
California |
|
| Stanford University Medical Center |
Stanford |
California |
|
| University of Colorado Denver |
Aurora |
Colorado |
|
| Advanced Neurosciences Research LLC |
Fort Collins |
Colorado |
|
| MS and Neuromuscular Center of Excellence |
Clearwater |
Florida |
|
| University of South Florida |
Tampa |
Florida |
|
| Baptist Health Lexington |
Nicholasville |
Kentucky |
|
| International Neurorehabilitation Institute |
Lutherville |
Maryland |
|
| Massachusetts General Hospital. |
Boston |
Massachusetts |
|
| University of Massachusetts Medical School |
Worcester |
Massachusetts |
|
| Michigan Institute for Neurological Disorders |
Farmington Hills |
Michigan |
|
| Washington University School of Medicine |
St Louis |
Missouri |
|
| Jersey Shore University Medical Centre |
Neptune City |
New Jersey |
|
| Northwell Health |
Great Neck |
New York |
|
| Lenox Hill Hospital |
New York |
New York |
|
| Cleveland Clinic |
Cleveland |
Ohio |
|
| Neurology Clinic PC |
Cordova |
Tennessee |
|
| Advanced Neurosciences Institute |
Nashville |
Tennessee |
|
| University of Texas Southwestern Medical Center |
Dallas |
Texas |
|
| Lone Star Neurology of San Antonio |
San Antonio |
Texas |
|
| Texas Institute for Neurological Disorders |
Sherman |
Texas |
|
| Wheaton Franciscan Healthcare - St. Francis Outpatient Center |
Milwaukee |
Wisconsin |
|
| CEMIC Saavedra |
Buenos Aires |
Argentina |
|
| Centro de Especialidades Neurológicas y Rehabilitación - CENyR |
Buenos Aires |
Argentina |
|
| INECO |
Rosario |
Argentina |
|
| Revalidatie en MS Centrum |
Overpelt |
Belgium |
|
| L2 Ip Instituto de Pesquisas Clinicas Ltda ME |
Brasília |
Federal District |
|
| Hospital das Clinicas - UFG |
Goiânia |
Goiás |
|
| Instituto de Neurologia de Curitiba |
Curitiba |
Paraná |
|
| Instituto Méderi de Pesquisa e Saúde |
Passo Fundo |
Rio Grande do Sul |
|
| Hospital Moinhos de Vento |
Porto Alegre |
Rio Grande do Sul |
|
| IMV Pesquisa Neurológica |
Porto Alegre |
Rio Grande do Sul |
|
| Hospital Sao Lucas - PUCRS |
Porto Alegre |
Rio Grande do Sul |
|
| Clinica Neurologica |
Joinville |
Santa Catarina |
|
| Hospital das Clinicas - UNICAMP |
Campinas |
São Paulo |
|
| Praxis Pesquisa Médica |
Santo André |
São Paulo |
|
| CPQuali Pesquisa Clinica Ltda |
São Paulo |
São Paulo |
|
| UMHAT Dr. Georgi Stranski |
Pleven |
Bulgaria |
|
+ 107 more sites — see the full list on the official registry below.
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