The HAM Infliximab Study (HAM06)

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

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.

Study Overview

• Status: Terminated
• Conditions: HTLV-I-associated Myelopathy
• Intervention / Treatment: Drug: Infliximab

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1PG
    • Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infliximab; 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; Infliximab 3mg/kg infused intravenously at weeks 0, 2 and 8 and then every 8 weeks until and including week 40 of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of clinical failure	48 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Medical Research Council
• Investigators: Principal Investigator: Graham P Taylor, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: January 14, 2009
• First Submitted That Met QC Criteria: January 14, 2009
• First Posted (Estimate): January 15, 2009

Study Record Updates

• Last Update Posted (Estimate): April 15, 2013
• Last Update Submitted That Met QC Criteria: April 12, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: HTLV-I; HAM/TSP
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Retroviridae Infections; Central Nervous System Infections; Myelitis; Deltaretrovirus Infections; HTLV-I Infections; Spinal Cord Diseases; Paraparesis, Tropical Spastic; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: cro948; EUDRACT: 2007-005554-23