Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate

NCT01569451 | Completed Phase 2 Results DMC

• 1 other identifier: 10-1143
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is (1) to determine if rituximab induction therapy followed by glatiramer acetate (GA) is substantially superior to placebo rituximab induction followed by GA for the treatment of clinically isolated syndrome (CIS) or relapsing forms of multiple sclerosis (RMS).

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Glatiramer Acetate; Rituximab; Relapsing forms of Multiple Sclerosis; Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Disease-free Patients

  Defined as patients without new lesions on brain MRI using the combined unique lesion approach (CUL), without sustained change in EDSS score over any 3-month period and without relapse. If a clear treatment effect is sustained in the R-GA arm, defined as a ≥ 70% decrease in brain lesions on MRI, using a CUL approach, attributable to MS and ≥ 70% reduction in annual relapse rates, compared to the GA arm, the study will continue under the extension protocol. If induction therapy fails to show superiority, at any point, the study will be stopped.

  Baseline through 24 months

Secondary Outcomes (9)

• Time to Treatment Failure

  Baseline through 24 months

• Number of Subjects That Fail Treatment

  Baseline through 24 months

• Number of Relapse-free Subjects

  Baseline through 24 months

• Number of Patients Treated for Relapse With Corticosteroid

  Baseline through 24 months

• Number of Subjects Who Experience Multiple Relapses

  Baseline through 24 months

Study Arms (2)

(Placebo and) Glatiramer Acetate

ACTIVE COMPARATOR

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily.

Drug: Glatiramer Acetate; Other: Placebo

Rituximab and Glatiramer Acetate (R-GA)

EXPERIMENTAL

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily. There is no placebo arm.

Drug: Rituximab; Drug: Glatiramer Acetate

Interventions

Rituximab DRUG

intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Also known as: Rituxan, MabThera

Rituximab and Glatiramer Acetate (R-GA)

Glatiramer Acetate DRUG

20 mg injected subcutaneously daily

Also known as: Copolymer 1, Cop-1, Copaxone

(Placebo and) Glatiramer Acetate; Rituximab and Glatiramer Acetate (R-GA)

Placebo OTHER

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab or placebo (normal saline) on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

(Placebo and) Glatiramer Acetate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• through 55 years of age
• Patients with CIS demonstrating one unifocal neurological event AND at least 2 T2-weighted brain lesions measuring a minimum of 6mm in diameter by MRI analysis; or a definite diagnosis of RMS, as defined by the 2005 revised McDonald criteria(1, 2), and have had at least one clinically defined relapse within the past year OR one GEL on an MRI within the past year
• Women of child-bearing potential must agree to practice an acceptable method of birth control
• No evidence of progressive multifocal leukoencephalopathy (PML) or primary central nervous system (PCNS) lymphoma
• Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization
• Subject must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with local regulatory requirements.

You may not qualify if:

• ≥ 15 GELs on baseline MRI
• Treatment with interferon β, natalizumab, or fingolimod within three months of randomization
• Treatment with mitoxantrone, cyclophosphamide, or any other chemotherapeutic agent for MS or malignancy within 12 months of randomization
• Attenuated live virus vaccination within 4 weeks of randomization
• Positive urine and serum pregnancy test at screening or baseline visit
• Any prior treatment with alemtuzumab or cladribine
• Unable to tolerate GA
• History of cardiac arrhythmias, angina or any other significant cardiac abnormalities
• History of clinically significant chronic disease of the immune system or a known immunodeficiency syndrome (HIV) other than MS
• White Blood Cell count of less than 2.5\*10\^9/L or lymphocyte count below 0.4\*10\^9/L
• Positive for any evidence of past, or current, hepatitis B and/or C infection
• History or presence of malignancy (except basal cell carcinoma)
• Clinically significant alcohol or drug abuse within past two years
• Any medical, psychiatric or other condition that could result in a subject not being able to give fully informed consent, or to comply with the protocol requirements
• Inability to undergo MRI scans or history of hypersensitivity to gadolinium- diethylenetriamine penta-acetic acid (DTPA)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Rocky Mountain MS Research Group, LLC: collaborator

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Honce JM, Nair KV, Sillau S, Valdez B, Miravalle A, Alvarez E, Schreiner T, Corboy JR, Vollmer TL. Rituximab vs placebo induction prior to glatiramer acetate monotherapy in multiple sclerosis. Neurology. 2019 Feb 12;92(7):e723-e732. doi: 10.1212/WNL.0000000000006916. Epub 2019 Jan 11.

  PMID: 30635477 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Rituximab; Glatiramer Acetate; Coat Protein Complex I

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Stefan Sillau
• Organization: University of Colorado

stefan.sillau@ucdenver.edu

303-724-8657

Study Officials

• Timothy Vollmer, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 3, 2012
• Study Start: February 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 8, 2018
• Results First Posted: June 7, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)