The HAM Infliximab Study

Study Overview
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Brief Summary
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An open-label, non-randomised, uncontrolled, proof-of-concept study of eight patients with 'definite' HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Eligible patients will have either early disease (of less than 2 years duration) or progressive disease (with observed clinical deterioration during the preceding 3 months. Following 2 baseline assessments including Magnetic Resonance Imaging (MRI) of the spinal cord and a lumbar puncture for examination of the fluid around the brain (CSF) participants will be treated with a total of 7 infusions of the anti-TNF-alpha antibody infliximab over a period of 48 weeks. After the last on therapy assessment at 48 weeks participants will be followed up for a further 24 weeks. Study assessments will be clinical, virological, immunological and radiological. MRIs of the spinal cord will be obtained at weeks 12 and 72. CSF will be examined, on therapy, at week 12.

Official Title
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An Open, Non-randomised Pilot Study of Anti-TNF-alpha Therapy in Early or Progressing HAM/TSP

Conditions
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HTLV-I-associated Myelopathy

Intervention / Treatment
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* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are able to give informed consent Are 16 years or older Have 'definite' HAM/TSP according to the criteria of Definite HAM/TSP agreed in Belem 200361 Have early or progressing disease as defined here: Early HAM/TSP: Patients must have motor disability (minimum of stiffness or weakness) for less than 2 years. (Bladder symptoms if the original and only presenting symptoms as assessed by history are not included) Progressing HAM/TSP New or worsening motor symptoms in a patient with definite HAM of > 2 years duration within the last 3 months Exclusion Criteria: Hepatitis B or hepatitis C infection HIV infection Overt sepsis, abscesses or opportunistic infections Active TB (untreated or on treatment) Strongyloides stercoralis (untreated) Known hypersensitivity to inflixmab, other murine proteins or to any of the excipients Malignancy Moderate or severe heart failure (NYHA class III/IV) Pregnancy or breastfeeding Unhealed surgical wounds Planned impending surgery - treatment would be withheld for 2-4 weeks prior to major surgery and started/restarted post-operatively if no evidence of infection and wound healing is satisfactory Current immunosuppressive or immunomodulatory therapy

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab<br>Infliximab 3mg/kg infused intravenously at weeks 0, 2 and 8 and then every 8 weeks until and including week 40 of the study | Drug: Infliximab<br>* Infliximab 3mg/kg infused intravenously at weeks 0, 2 and 8 and then every 8 weeks until and including week 40 of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical failure |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in timed 10m walk |  | 12, 24, 48 and 72 weeks | 
| Clinical Safety |  | 48 weeks | 
| HTLV-I viral load in CSF |  | 12 weeks | 
| HTLV-I viral load in peripheral blood |  | 12, 24, 48 and 72 weeks | 
| % CD4+ T- lymphocytes expressing CD25 |  | 24, 48 and 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAM/TSP, HTLV-I