- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00087529
A Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis (OLYMPUS)
10. august 2015 opdateret af: Genentech, Inc.
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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
439
Fase
- Fase 2
- Fase 3
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 65 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
- 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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: 1
|
Intravenøs gentagen dosis
|
Placebo komparator: 2
|
Intravenøs gentagen dosis
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Time to Confirmed Disease Progression (CDP)
Tidsramme: 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.
|
96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
|
Percentage of Participants With CDP
Tidsramme: 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.
|
96 weeks (from Screening to Week 96, and at least 12 weeks after initial progression)
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Change From Baseline to Week 96 in Total Volume of Transverse Relaxation Time (T2) Brain Lesions on Magnetic Resonance Imaging (MRI) Scan
Tidsramme: At Baseline and Week 96
|
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).
|
At Baseline and Week 96
|
Change From Baseline to Week 96 in Brain Volume on MRI Scan
Tidsramme: At Baseline and Week 96
|
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).
|
At Baseline and Week 96
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studieleder: Craig Smith, M.D., Genentech, Inc.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Zhang 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.
- Hawker 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juni 2004
Primær færdiggørelse (Faktiske)
1. oktober 2007
Datoer for studieregistrering
Først indsendt
9. juli 2004
Først indsendt, der opfyldte QC-kriterier
12. juli 2004
Først opslået (Skøn)
13. juli 2004
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
9. september 2015
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
10. august 2015
Sidst verificeret
1. august 2015
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Sygdomme i nervesystemet
- Sygdomme i immunsystemet
- Demyeliniserende autoimmune sygdomme, CNS
- Autoimmune sygdomme i nervesystemet
- Demyeliniserende sygdomme
- Autoimmune sygdomme
- Multipel sclerose
- Multipel sklerose, kronisk progressiv
- Sclerose
- Lægemidlers fysiologiske virkninger
- Antirheumatiske midler
- Antineoplastiske midler
- Immunologiske faktorer
- Antineoplastiske midler, immunologiske
- Rituximab
Andre undersøgelses-id-numre
- U2786g
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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