Multiple SclerosisPhase 2/3OLYMPUSNCT00087529
A Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis
A Phase 2/3 study testing rituximab in people with Multiple Sclerosis, run by Genentech, Inc..
Trial summary
This is a Phase II/III, randomized, double-blind, parallel group, placebo controlled, multicenter study to evaluate the safety and efficacy of rituximab in adults with PPMS. The study will enroll approximately 435 subjects at up to 60 sites in the United States and Canada. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 439 participants
- Where
- No sites listed yet
- Study dates
- Jun 2004to Oct 2007
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Definitive diagnosis of PPMS
- Disease duration of ≥ 1 year
- EDSS at baseline between 2.0 and 6.5 points, inclusive
- Score of ≥ 2.0 on the Functional Systems (FS) scale for the pyramidal system or gait that is due to lower extremity findings
- Presence of at least one of the following in a CSF specimen obtained during the screening period and analyzed by the central laboratory or results from a CSF sample obtained during the previous 24 months:
- For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) during study treatment and for 1 year following the last dose of study drug
Who cannot join
- Pregnancy or lactation
- Incompatibility with MRI
- Lack of peripheral venous access
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Known active bacterial, viral, fungal, mycobacterial, or other infection (including atypical mycobacterial disease, but excluding fungal infections of nail beds or recurrent herpes zoster or simplex infections) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 30 days prior to screening or oral antibiotics within 14 days prior to screening
- History or presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis)
Show all 30Show fewer
- History of cancer, including solid tumors and hematologic malignancies (except resected and fully resolved cutaneous basal cell and squamous cell carcinomas)
- History of alcohol or drug abuse within 6 months prior to screening
- History of or currently active primary or secondary immunodeficiency
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
- Presence of other significant, uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease that might interfere with a subject's ability to participate and to complete approximately 2.5 years of study participation
- History or presence of MS relapse or exacerbation
- History or presence of vascular disease potentially affecting the brain or spinal cord (e.g., stroke, transient ischemic attack, carotid stenosis, aortic aneurysm, intracranial aneurysm, hemorrhage, arteriovenous malformation)
- History or presence of myelopathy due to spinal cord compression by disk or vertebral disease
- History of severe, clinically significant central nervous system trauma (e.g., cerebral contusion, spinal cord compression)
- History of intracranial or intraspinal tumor (e.g., meningioma, glioma)
- History or presence of potential metabolic cause of myelopathy or encephalopathy (e.g., vitamin B12 deficiency, thyroid abnormalities)
- History or presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-cell lymphotropic virus type 1 [HTLV-1], or herpes zoster myelopathy)
- History of genetically inherited progressive CNS degenerative disorder (e.g., X-linked adrenoleukodystrophy, hereditary spastic paraparesis)
- Neuromyelitis optica
- History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sj�gren syndrome, Beh�et disease)
- History or presence of sarcoidosis
- Previous treatment with rituximab (MabThera(R)/Rituxan(R))
- Previous treatment with lymphocyte-depleting therapies (e.g., cyclophosphamide, Campath(R), anti-CD4, cladribine, total body irradiation, bone marrow transplantation), except mitoxantrone, which should not be used 12 months prior to randomization
- Treatment with an investigational agent within 90 days or 5 half-lives of the investigational drug (whichever is longer) prior to randomization
- Receipt of a live vaccine within 30 days prior to randomization
- Systemic corticosteroid therapy within 30 days prior to randomization
- Treatment with IFN-\β, glatiramer acetate, IVIg, or plasmapheresis within 60 days prior to randomization
- Treatment with non-lymphocyte-depleting immunosuppressive therapies (e.g., azathioprine, mycophenolate mofetil [MMF], cyclosporine) within 90 days prior to randomization
- Statins or hormone replacement therapy started within 30 days prior to randomization
About this study
Official title: A Phase II/III, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis
This is a Phase II/III, randomized, double-blind, parallel group, placebo controlled, multicenter study to evaluate the safety and efficacy of rituximab in adults with PPMS. The study will enroll approximately 435 subjects at up to 60 sites in the United States and Canada.
- Conditions
- Multiple Sclerosis
- Being tested
- placebo, rituximab
- Keywords
- PPMS, Primary progressive MS, Primary progressive multiple sclerosis, Rituxan, MS
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
Intravenous repeating dose
rituximabDrug
Intravenous repeating dose
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: rituximab |
| 2 | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Confirmed Disease Progression (CDP)
Disease progression was assessed using the Expanded Disability Status Scale (EDSS), a disability scale that ranges from 0 to 10, where higher scores represent increased disability. Progression was defined as either an increase of greater than or equal to (≥) 1 point from a Baseline EDSS score within 2.0 to 5.5 points, or an increase of ≥0.5 points from a Baseline EDSS score greater than (>) 5.5 points, for which the change was not attributable to another etiology. Repeat assessment to determine CDP must have occurred at a regularly scheduled visit at least 12 weeks after initial progression; those who discontinued treatment early without confirmatory EDSS assessment were considered as having CDP. Those who did not meet criteria for CDP, completed treatment with only initial progression, or received an exclusionary therapy were censored at last EDSS assessment. Time to CDP was the time from randomization to initial disease progression, estimated using Kaplan-Meier (KM) analysis.
Measured: 96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
Percentage of Participants With CDP
Disease progression was assessed using the EDSS, a disability scale that ranges from 0 to 10, where higher scores represent increased disability. Progression was defined as either an increase of ≥1 point from a Baseline EDSS score within 2.0 to 5.5 points, or an increase of ≥0.5 points from a Baseline EDSS score >5.5 points, for which the change was not attributable to another etiology. Repeat assessment to determine CDP must have occurred at a regularly scheduled visit at least 12 weeks after initial progression; those who discontinued treatment early without confirmatory EDSS assessment were considered as having CDP. The percentage of participants with CDP was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.
Measured: 96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
Secondary outcomes (2)
Change From Baseline to Week 96 in Total Volume of Transverse Relaxation Time (T2) Brain Lesions on Magnetic Resonance Imaging (MRI) Scan
Scheduled T2-weighted MRI scans of the brain and cervical spinal cord were performed with and without gadolinium contrast at Screening and Week 6, and without gadolinium at Weeks 48, 96, and 122 and/or upon early termination. The total volume of T2 (ie, hyperintense) brain lesions at each visit was documented. Missing Week 96 values were imputed using a last observation carried forward (LOCF) approach, while participants with missing Baseline values were excluded. The change in T2 lesion volume was calculated as [volume at Week 96 minus volume at Baseline] and expressed in cubic millimeters (mm^3).
Measured: At Baseline and Week 96
Change From Baseline to Week 96 in Brain Volume on MRI Scan
Scheduled MRI scans of the brain and cervical spinal cord were performed with and without gadolinium contrast at Screening and Week 6, and without gadolinium at Weeks 48, 96, and 122 and/or upon early termination. The total brain volume was documented at Baseline and at visits occurring during Weeks 48 and 96. Missing Week 96 values were imputed using a LOCF approach, while participants with missing Baseline values were excluded. The change in brain volume was calculated as [volume at Week 96 minus volume at Baseline] and expressed in cubic centimeters (cm^3).
Measured: At Baseline and Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2004 (estimated)
- Study startJun 2004
- Primary completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 439 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Craig Smith, M.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00087529
- Sponsor's protocol ID
- U2786g
- Acronym
- OLYMPUS
- Status last verified
- Aug 2015
- First submitted
- 9 Jul 2004
- Last updated
- 9 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.
PubMed 40258203Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.
PubMed 36163349Zhang J, Waubant E, Cutter G, Wolinsky JS, Glanzman R. EDSS variability before randomization may limit treatment discovery in primary progressive MS. Mult Scler. 2013 May;19(6):775-81. doi: 10.1177/1352458512459685. Epub 2012 Oct 1.
PubMed 23027880Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71. doi: 10.1002/ana.21867.
PubMed 19847908
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00087529
- Acronym / sponsor ID
- OLYMPUS / U2786g
- Conditions
- Multiple Sclerosis
- Keywords
- PPMS, Primary progressive MS, Primary progressive multiple sclerosis, Rituxan, MS
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 439 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2004
- Primary completion
- Oct 2007 (actual)
- First posted
- 13 Jul 2004 (estimated)
- Results
- Posted 9 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II/III, randomized, double-blind, parallel group, placebo controlled, multicenter study to evaluate the safety and efficacy of rituximab in adults with PPMS. The study will enroll approximately 435 subjects at up to 60 sites in the United States and Canada.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rituximab |
| 2 | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Definitive diagnosis of PPMS
- Disease duration of ≥ 1 year
- EDSS at baseline between 2.0 and 6.5 points, inclusive
- Score of ≥ 2.0 on the Functional Systems (FS) scale for the pyramidal system or gait that is due to lower extremity findings
- Presence of at least one of the following in a CSF specimen obtained during the screening period and analyzed by the central laboratory or results from a CSF sample obtained during the previous 24 months:
Key exclusion criteria (30 listed)
- Pregnancy or lactation
- Incompatibility with MRI
- Lack of peripheral venous access
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Known active bacterial, viral, fungal, mycobacterial, or other infection (including atypical mycobacterial disease, but excluding fungal infections of nail beds or recurrent herpes zoster or simplex infections) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 30 days prior to screening or oral antibiotics within 14 days prior to screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboIntravenous repeating dose | Drug | 2 |
| rituximabIntravenous repeating dose | Drug | 1 |
Primary outcome
Time to Confirmed Disease Progression (CDP)
Time frame: 96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
Disease progression was assessed using the Expanded Disability Status Scale (EDSS), a disability scale that ranges from 0 to 10, where higher scores represent increased disability. Progression was defined as either an increase of greater than or equal to (≥) 1 point from a Baseline EDSS score within 2.0 to 5.5 points, or an increase of ≥0.5 points from a Baseline EDSS score greater than (>) 5.5 points, for which the change was not attributable to another etiology. Repeat assessment to determine CDP must have occurred at a regularly scheduled visit at least 12 weeks after initial progression; those who discontinued treatment early without confirmatory EDSS assessment were considered as having CDP. Those who did not meet criteria for CDP, completed treatment with only initial progression, or received an exclusionary therapy were censored at last EDSS assessment. Time to CDP was the time from randomization to initial disease progression, estimated using Kaplan-Meier (KM) analysis.
Percentage of Participants With CDP
Time frame: 96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
Disease progression was assessed using the EDSS, a disability scale that ranges from 0 to 10, where higher scores represent increased disability. Progression was defined as either an increase of ≥1 point from a Baseline EDSS score within 2.0 to 5.5 points, or an increase of ≥0.5 points from a Baseline EDSS score >5.5 points, for which the change was not attributable to another etiology. Repeat assessment to determine CDP must have occurred at a regularly scheduled visit at least 12 weeks after initial progression; those who discontinued treatment early without confirmatory EDSS assessment were considered as having CDP. The percentage of participants with CDP was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.
2 secondary outcomes
Change From Baseline to Week 96 in Total Volume of Transverse Relaxation Time (T2) Brain Lesions on Magnetic Resonance Imaging (MRI) Scan
Time frame: At Baseline and Week 96
Change From Baseline to Week 96 in Brain Volume on MRI Scan
Time frame: At Baseline and Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40258203Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.
- Derived from this study: PubMed 36163349Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.
- Derived from this study: PubMed 23027880Zhang J, Waubant E, Cutter G, Wolinsky JS, Glanzman R. EDSS variability before randomization may limit treatment discovery in primary progressive MS. Mult Scler. 2013 May;19(6):775-81. doi: 10.1177/1352458512459685. Epub 2012 Oct 1.
- Derived from this study: PubMed 19847908Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71. doi: 10.1002/ana.21867.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Smith, M.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rituximab in people with Multiple Sclerosis, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Confirmed Disease Progression (CDP) (time frame: 96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00087529, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2015.