Clinical trial NCT00823641: The HAM Infliximab Study
Official title: An Open, Non-randomised Pilot Study of Anti-TNF-alpha Therapy in Early or Progressing HAM/TSP
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HTLV-I-associated Myelopathy
Keywords: HAM/TSP
HTLV-I
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
First posted: 2009-01-15
Enrollment: 3
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of clinical failure
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in timed 10m walk
timeFrame: 12, 24, 48 and 72 weeks
measure: Clinical Safety
timeFrame: 48 weeks
measure: HTLV-I viral load in CSF
timeFrame: 12 weeks
measure: HTLV-I viral load in peripheral blood
timeFrame: 12, 24, 48 and 72 weeks
measure: % CD4+ T- lymphocytes expressing CD25
timeFrame: 24, 48 and 72 hours
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Graham P Taylor, MD
role: PRINCIPAL_INVESTIGATOR
References: