Active, not recruiting
Phase 3
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Condition(s) studied
Multiple Sclerosis, Primary Progressive
Investigational drug(s) / intervention(s)
OcrelizumabPlacebo
Ocrelizumab: The first dose of ocrelizumab will be administered as two 300 milligrams (mg), IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg infusion every 24 weeks. A minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusion, should be maintained between each infusion.
Placebo: The first dose of placebo will be administered as two IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusions, maintained between each infusion.
Study summary
This study will evaluate the efficacy and safety of ocrelizumab (Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study will consist of the following phases: screening, double-blind treatment, an optional post-double-progression ocrelizumab (PDP OCR) treatment, follow-up 1 (FU1), an optional open-label extension (OLE), and follow-up 2 (FU2).
Eligibility
Inclusion Criteria:
* EDSS score at screening and baseline \>= 3.0 to 8.0, inclusive
* Disease duration from the onset of MS symptoms relative to randomization date:
Less than 20 years in participants with an EDSS score at screening 7.0 - 8.0 Less than 15 years in participants with an EDSS at screening 5.5 - 6.5 Less than 10 years in participants with an EDSS at screening \<= 5.0
* Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated immunoglobulin G (IgG) index or one or more IgG oligoclonal bands detected by isoelectric focusing
* Screening and baseline 9-HPT completed in \> 25 seconds (average of the two hands)
* Neurological stability for ≥ 30 days prior to baseline
* Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline
* Neurological stability for \>/= 30 days prior to baseline
* Participants previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
* For female participants without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile
Exclusion Criteria:
* History of relapsing-remitting or secondary progressive MS at screening
* Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease
* Participants who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)
* Known active malignancy or are being actively monitored for recurrence of malignancy
* Immunocompromised state
* Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
* Inability to complete an MRI or contraindication to Gd administration.
* Participants requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Participants must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization.
* Contraindications to mandatory premedications for infusion-related reactions, including:
uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines
* Known presence of other neurologic disorders
* Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months after last infusion of the study drug
* Lack of peripheral venous access
* Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude participant from participating in the study
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of alcohol or other drug abuse
* History of primary or secondary immunodeficiency
* Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS
* Previous treatment with B-cell targeting therapies
* Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
* Any previous history of transplantation or anti-rejection therapy
* Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
* Systemic corticosteroid therapy within 4 weeks prior to screening
* Positive serum human chorionic gonadotropin (hCG) measured at screening or positive urine β-hCG at baseline
* Positive screening tests for hepatitis B
* Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above
* Lack of MRI activity at screening/baseline if more than 650 participants without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 participants with MRI activity will be randomized
Eligibility Criteria for OLE Phase:
* Completed the 144 weeks of double-blind treatment phase of the trial or are ongoing in the double blind treatment phase at the time of the primary analysis, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Participants who withdrew from study treatment and received another DMT or commercial ocrelizumab will not be allowed to enter in the OLE phase.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
* For female participants without reproductive potential: Women may be enrolled if surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile
Primary outcome measure(s)
- Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) in FAS — Up to approximately 243 weeks
Time to onset of cCDP12=time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-hole Peg Test (9-HPT) confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in Expanded Disability Status Scale (EDSS) score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
- Time to Onset of cCDP12 in Magnetic Resonance Imaging (MRI) Activity Analysis Set — Up to approximately 243 weeks
Time to onset of cCDP12 was defined as the time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in EDSS score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of \>5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems \& ambulation, that ranges in 0.5-point steps from 0 \[normal\] to 10.0 \[death\]. 9-HPT is a quantitative measure of arm \& hand function, where participants placed \& removed pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Trial sites (155)
| Facility | City | Region | Status |
| Georgetown University Medical Center |
Washington D.C. |
District of Columbia |
|
| MS and Neuromuscular Center of Excellence |
Clearwater |
Florida |
|
| Neurological Services of Orlando |
Orlando |
Florida |
|
| Vero Neurology |
Vero Beach |
Florida |
|
| University of Kansas Medical Center |
Kansas City |
Kansas |
|
| The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company |
Columbus |
Ohio |
|
| Columbus Neuroscience |
Westerville |
Ohio |
|
| Albert Einstein Medical Center |
Philadelphia |
Pennsylvania |
|
| Brain and Mind Research Institute |
Camperdown |
New South Wales |
|
| Austin Hospital |
Heidelberg |
Victoria |
|
| Royal Melbourne Hospital |
Parkville |
Victoria |
|
| UZ Antwerpen |
Edegem |
Antwerpen |
|
| Cliniques Universitaires St-Luc |
Brussels |
Belgium |
|
| MS & Neurologisch Revalidatie Centrum |
Overpelt |
Belgium |
|
| Military Medical Academy HBAT |
Pleven |
Bulgaria |
|
| Multiprofile Hospital For Active Treatment Avis Medica |
Pleven |
Bulgaria |
|
| Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD |
Sofia |
Bulgaria |
|
| University of Alberta |
Edmonton |
Alberta |
|
| Dalhousie Multiple Sclerosis Research Unit |
Halifax |
Nova Scotia |
|
| St. Michael's Hospital |
Toronto |
Ontario |
|
| Recherche Sepmus Inc. |
Greenfield Park |
Quebec |
|
| Instituto Neurologico de Colombia INDEC |
Medellín |
Antioquia |
|
| Clinica Colsanitas S.A. sede Clinica Universitaria Colombia |
Bogotá |
Colombia |
|
| General Hospital Varazdin |
Varaždin |
Croatia |
|
| Clinical Hospital Sestre Milosrdnice |
Zagreb |
Croatia |
|
| University Hospital Center Zagreb |
Zagreb |
Croatia |
|
| CHU de Bordeaux - Hôpital Pellegrin |
Bordeaux |
France |
|
| Centre Hospitalier Universitaire de Clermont Ferrand |
Clermont-Ferrand |
France |
|
| CHRU Nancy |
Nancy |
France |
|
| Hopital Guillaume Et Rene Laennec |
Nantes |
France |
|
| CHU de Nimes - Hopital Universitaire Caremeau |
Nîmes |
France |
|
| Hopital Civil |
Strasbourg |
France |
|
| Pineo Medical Ecosystem LTD |
Tbilisi |
Georgia |
|
| The First University Clinic of Tbilisi State Medical University |
Tbilisi |
Georgia |
|
| Khechinashvili University Hospital |
Tbilisi |
Georgia |
|
| AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2 |
Naples |
Campania |
|
| Fondazione PTV Policlinico Tor Vergata |
Rome |
Lazio |
|
| Azienda Ospedaliera Sant'andrea |
Rome |
Lazio |
|
| IRCCS AOM Azienda Ospedaliera Metropolitana |
Genoa |
Liguria |
|
| Ospedale San Raffaele S.r.l. - PPDS |
Milan |
Lombardy |
|
+ 115 more sites — see the full list on the official registry below.
More Hoffmann-La Roche trials in the UK
Other trials for the same condition