A Study to Evaluate the Safety and Efficacy of Rituximab in Adults With Primary Progressive Multiple Sclerosis

NCT00087529 | Completed Phase 2 Results

• 1 other identifier: U2786g
• Study Type: interventional
• Target: 439
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Multiple Sclerosis

Keywords

PPMS; Primary progressive MS; Primary progressive multiple sclerosis; Rituxan; MS

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  At Baseline and Week 96

• Change From Baseline to Week 96 in Brain Volume on MRI Scan

  At Baseline and Week 96

Study Arms (2)

1

EXPERIMENTAL

Drug: rituximab

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

placebo DRUG

Intravenous repeating dose

2

rituximab DRUG

Intravenous repeating dose

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (4)

• 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.

  PMID: 40258203 DERIVED

• Falet 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.

  PMID: 36163349 DERIVED

• 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.

  PMID: 23027880 DERIVED

• 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.

  PMID: 19847908 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Craig Smith, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 9, 2004
• First Posted: July 13, 2004
• Study Start: June 1, 2004
• Primary Completion: October 1, 2007
• Last Updated: September 9, 2015
• Results First Posted: September 9, 2015

Record last verified: 2015-08