Hu Mik-Beta-1 to Treat HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

NCT00076843 | Completed Phase 1 FDA Drug

• 2 other identifiers: 04007104-N-0071
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the use of the humanized Mik-Beta-1 (Hu Mik-(SqrRoot) 1) monoclonal antibody in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Some patients infected with the human T-lymphotropic virus type 1 (HTLV-1) virus develop HAM/TSP, a disease in which the immune response to HTLV-1 becomes directed against the person's own body in what is called an autoimmune response. Hu-Mik-Beta-1 is a genetically engineered antibody that blocks the action of a chemical produced by the body during infection or inflammation called interleukin 15 (IL-15). Blocking IL-15 may prevent the autoimmune response that results in HAM/TSP. Patients 18 years of age and older with HAM/TSP may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and an electrocardiogram. Participants undergo the following procedures:

• Lumbar puncture: A local anesthetic is injected to numb the skin of the lower back. A needle is inserted in the space between the bones where the cerebrospinal fluid that bathes the brain and spinal cord circulates below the spinal cord. About 4 tablespoons of fluid is collected through the needle.
• Magnetic resonance imaging (MRI): This test uses radio waves and magnets to produce images of body tissues and organs. The patient lies on a table that slides into a metal cylinder surrounded by a strong magnetic field. During part of the scan, a contrast agent is injected to brighten the images.
• Apheresis: This procedure is used to collect large quantities of white blood cells. Whole blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by spinning. The white cells and plasma are removed and the rest of the blood (red cells and platelets) is returned to the body through the same needle.
• Hu Mik-Beta-1 treatment: Infusions of Hu Mik-Beta-1 are given through a vein every 3 weeks for nine doses. The first treatment requires at least an overnight hospital stay; subsequent infusions are given in the outpatient clinic.
• Blood and urine tests and a physical examination at every treatment visit and a skin test at one treatment visit.
• Research tests at the end of the 24-week treatment period, including lumbar puncture (spinal tap), MRI scan, and apheresis.
• After completing treatment, patients have three follow-up clinic visits for blood and urine tests, and a skin test at one follow-up visit.

Conditions

HTLV-1

Keywords

Interleukin-15; CD8+ T-cells; HAM/TSP; HTLV-1; HTLV-1 Associated Myelopathy; Tropical Spastic Paraparesis

Interventions

Hu MiK-Beta-1 DRUG

Eligibility Criteria

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

You may qualify if:

• Patients must be at least 18 years old.
• Patients must have a diagnosis of HAM/TSP as defined by the WHO criteria, including a positive HTLV-I EIA and confirmatory pattern on Western Blot analysis. Other causes of chronic progressive myelopathy are excluded by tests for serum B12 level, Lyme disease serologies, RPR, anti-nuclear antibody (ANA), extractable nuclear antigen (ENA) screen and magnetic resonance images of brain and spinal cord.
• At least 7% of each patient's peripheral blood mononuclear cell population must react with anti-CD122 immunofluorescent cell staining.
• Spontaneous lymphoproliferation and HTLV-I specific cytotoxic T lymphocyte responses must be demonstrated by the patient's peripheral blood mononuclear cells in ex vivo culture.
• Patients must be willing to comply with all aspects of the dosing and evaluation procedure including taking the required medications and should be willing to return for the follow-up visits.
• Patients must be able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.

You may not qualify if:

• EDSS greater than or equal to 7 (unable to walk beyond approximately 5 meters even with aid, essentially restructed to wheelchair).
• Any contraindication to monoclonal antibody therapy, including serious adverse events related to prior monoclonal antibody therapy. Patients who have received prior antibody therapy will have pertinent medical records reviewed by the study investigator. Subjects with prior monoclonal antibody use (especially murine MiK- Beta 1) and allergy/sensitivity to murine MiK- Beta 1 are excluded.
• Any vaccination within 30 days prior to study entry.
• Any chronic bacterial, mycobacterial, other viral (e.g. herpes virus), fungal, parasitic or protozoal infection.
• History of malignancy (active or within the previous 5 years).
• History or signs of immunodeficiency
• Subjects with pre-existing cardiac disease, abnormal baseline echocardiogram or significantly abnormal ECG will undergo evaluation by a cardiologist, and will be excluded if, in the opinion of the cardiologist, participation in the study would compromise the safety of the patient.
• Subjects with history or laboratory evidence of thrombosis or hypercoagulable state.
• Concurrent medical condition that in the opinion of the investigator would compromise the safety of the patient.
• HAM/TSP patients with co-existing HTLV-I associated medical conditions, such as uveitis, alveolitis or keratoconjunctivitis sicca are not excluded unless, in the opinion of the investigator, participation in the protocol would compromise the safety of the patient. However, patients with clinically significant co-morbid neuromuscular conditions such as inflammatory myopathies and neuropathies are excluded.
• Patients with cognitive impairment who are unable to provide written, informed consent.
• The patient has received an investigational drug for this condition within 6 months prior to entering the study.
• Contraindication to prophylactic anticoagulation with low molecular weight heparin such as history of hypersensitivity to enoxaparin, haparin, pork products, or any component of the formulation (including benzyl alcohol in multiple-dose vials); thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of enoxaparin
• The patient requires concurrent therapy with other immuno-modulating agents including interferons, corticosteroids and daclizumab.
• Serious illness requiring systemic treatment and /or hospitalization until the subject either completes therapy or is clinically stable (in the opinion of the investigator) on therapy for at least 14 days prior to the first dose.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gessain A, Gout O. Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). Ann Intern Med. 1992 Dec 1;117(11):933-46. doi: 10.7326/0003-4819-117-11-933.

  PMID: 1443956 BACKGROUND

• Itoyama Y, Minato S, Kira J, Goto I, Sato H, Okochi K, Yamamoto N. Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. Neurology. 1988 Aug;38(8):1302-7. doi: 10.1212/wnl.38.8.1302.

  PMID: 2899862 BACKGROUND

• Jacobson S, Shida H, McFarlin DE, Fauci AS, Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245-8. doi: 10.1038/348245a0.

  PMID: 2146511 BACKGROUND

MeSH Terms

Conditions

Paraparesis, Tropical Spastic

Interventions

Hu-Mik-beta-1 monoclonal antibody

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; HTLV-I Infections; Deltaretrovirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases

Study Officials

• Steven Jacobson, Ph.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2006
• First Posted: February 4, 2004
• Study Start: February 3, 2004
• Primary Completion: October 11, 2017
• Study Completion: June 25, 2019
• Last Updated: June 27, 2019

Record last verified: 2019-06-25

Locations

US (1)