Safety and Tolerability of Rituximab in Neuromyelitis Optica

NCT00501748 | Completed Phase 1 DMC

• 1 other identifier: H7620-25392-04
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this research study is to investigate whether Rituximab is safe to use in patients suffering from NMO, or who are at high risk for developing NMO. It is thought that NMO is caused by the immune system reacting against the optic nerves and spinal cord. B cells are a part of the immune system that may contribute to the illness. Rituximab is an antibody that depletes B cells. Depletion of these B cells with Rituximab may induce remission of the disease. Because pathological and serological studies suggest that NMO appears to be, at least in part, a B-cell mediated disease Rituximab, is an attractive treatment candidate for this disease.

Conditions

Neuromyelitis Optica

Keywords

Neuromyelitis Optica; acute transverse myelitis

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Rituximab in NMO (monitor for any AE during two years of follow up)

  96 weeks

Secondary Outcomes (2)

• Time from treatment to recurrence of either optic neuritis or myelitis

  96 weeks

• Change in Kurtzke expanded disability status scale (EDSS) at weeks 4, 12, 24, 48, 72, 96

  96 weeks

Study Arms (1)

Rituximab

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab is a highly purified, 1328-amino acid antibody with an approximate molecular mass of 145 kD. Rituximab is a sterile, clear, colorless, preservative-free liquid concentrate for intravenous (IV) administration. Rituximab is supplied at a concentration of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-use vials. In this single arm study all subjects are treated with two cycles of rituximab. Each cycle consists of two 1000 mg infusions administered two weeks apart. The cycles of rituximab treatment are administered at baseline and at 9 months.

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 12 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Criteria for neuromyelitis optica:
• acute transverse myelitis and optic neuritis occurring within 30 days of each other followed by a second attack of either optic neuritis and/or acute transverse myelitis at least 3 months following the heralding attack OR
• acute transverse myelitis followed by optic neuritis at least 3 months later OR
• optic neuritis followed by acute transverse myelitis at least 3 months later
• Criteria for high risk for neuromyelitis optica:
• recurrent idiopathic recurrent acute transverse myelitis with at least 3 months time between each attack OR
• recurrent bilateral simultaneous optic neuritis with at least 3 months time between each attack.
• Subjects should also have no clinical evidence of disease outside the optic nerve or spinal cord.
• In addition patients should have one major supportive criteria OR two minor supportive criteria:
• Negative brain MRI at onset (Does not meet criteria for multiple sclerosis (Paty, 1998)
• Spinal cord MRI with signal abnormality extending over ≥3 vertebral segments
• CSF pleocytosis of \> 50 WBC/mm3 OR \> 5 PMNs/mm3
• Minor supportive criteria:
• Bilateral optic neuritis
• Severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye

You may not qualify if:

• Treatment with broad-spectrum immunosuppressant medications such as cyclophosphamide, mitoxantrone, methotrexate, azathioprine, and cladribine, within 60 days of screening.
• Treatment with any investigational agent within 4 weeks of screening
• Receipt of a live vaccine within 4 weeks prior to randomization
• Previous Treatment with Rituximab (MabThera® / Rituxan®)
• Prior antibody therapy
• History of exposure to clioquinol
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of HIV (positive HIV, HIV conducted during screening if applicable)
• History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral fungal mycobacterial, or other infection or any major episode of infection requiring hospitalization
• Ongoing daily steroid use
• History of drug, alcohol, or chemical abuse within 6 months prior to screening
• Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genentech, Inc.: collaborator

Study Sites (2)

UCSF MS Center , 350 Parnassus Ave , suite #908

San Francisco, California, 94117, United States

Location

The Neurological Institute of New York MS Center

Columbia University Medical Center 710 West 168th Street,, New York, 10032, United States

Location

MeSH Terms

Conditions

Neuromyelitis Optica; Myelitis, Transverse

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis; Central Nervous System Infections; Infections; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Central Nervous System Diseases; Spinal Cord Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Bruce Cree, MD, PhD

  MS Center , UCSF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2007
• First Posted: July 16, 2007
• Study Start: January 1, 2004
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: September 27, 2011

Record last verified: 2011-09

Locations

US (2)