Acute Safety, Tolerability, Feasibility and Pharmacokinetics of Intrath. Administered ATI355 in Patients With Acute SCI

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00406016
First received: November 30, 2006
Last updated: November 2, 2011
Last verified: November 2011
  Purpose

This study will evaluate the acute safety, tolerability, feasibility and pharmacokinetics of 6 dose regimens of ATI355 in acute spinal cord injury patients


Condition Intervention Phase
Acute Spinal Cord Injury
Drug: ATI355
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Cohort Study to Assess Feasibility, Acute Safety, Tolerability and Pharmacokinetics of 4 Dose Regimens of Continuous Intrathecal ATI355 Infusion and Two Regimen of Repeated Intrathecal Bolus Injections in Acute Spinal Cord Injury Paraplegic and Tetraplegic Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Feasibility, Safety and Tolerability of a continuous intrathecal (i.t.) infusion or i.t. repeated bolus injections of ATI355 in patients with acute spinal cord injury at every visit and Assessment of serum and CSF pharmacokinetics at predefined visits. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity of ATI355 in acute spinal cord injury patients up to one year. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Early potential signal of efficacy by the American Spinal Cord Injury Association (ASIA) protocol and pharmacodynamic changes assessed by electrophysiology tests for up to one year. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: May 2006
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: ATI355

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Acute spinal cord injury paraplegic and tetraplegic patients with confirmed classification of ASIA A (C5 ≤ lesion ≤ T12; 4-14 days post-injury (i.e. study drug treatment must begin 4-14 days post injury) for paraplegic patients and for those tetraplegic patients who do not require artificial respiration at time of treatment initiation within the 4-14 days time interval. In those tetraplegic patients who still require artificial respiration in the 4-14 days time interval treatment can be initiated up to 60 days post-injury as soon as the patient is weaned off the respiratory machine.)
  • Tetraplegic patients who were initially diagnosed as ASIA A (neurologically complete lesion) at screening and turned into ASIA B (neurologically incomplete lesion) at baseline.
  • Hemodynamically stable (at baseline).
  • For female patients of child bearing potential, written agreement to abstain from intercourse during the first 12 weeks of the study and then subsequent use of a double-barrier local contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom for up to one year post study drug treatment. Patients must receive documented counseling on contraceptive measures.
  • For Cohort 5: Acute spinal cord injury tetraplegic patients with confirmed classification of ASIA A: Cervical lesions (C5 ≤ lesion ≤ T1). 4-28 days post-injury (i.e. study drug treatment must begin 4-28 days post injury). Tetraplegic patients who are allowed to start treatment are those who either do not require mechanical ventilation or who do not completely depend on mechanical ventilation but show some degree of spontaneous ventilation. Only those modes of ventilation where the patient must initiate all breaths are allowed (e.g. continuous positive airway pressure [CPAP]).

Exclusion criteria

  • Complete anatomical transection confirmed by MRI or trauma caused by ballistic or other injury that directly penetrates the spinal cord including gunshot and knife wounds.
  • Magnetic Resonance Imaging (MRI) indicating complete obstruction of the intrathecal space.
  • Presence of one of the following:
  • multiple spinal cord lesions
  • cauda equina damage
  • major brachial or lumbar plexus damage/trauma
  • significant head trauma (e.g. cortical damage/lesion), or other injury that was, in the opinion of the investigator, sufficient to interfere with the assessment of the spinal cord function or otherwise compromise the validity of the patient's data.
  • Other significant preexisting or current systemic disease such as lung, liver (exception: history of uncomplicated Hepatitis A), gastrointestinal, cardiac, immunodeficiency (including human immunodeficiency virus [HIV]) or kidney disease; or active malignancy or any other condition as determined by history or laboratory investigation that could cause a neurological deficit including syphilis, myelopathy, clinically relevant polyneuropathy, etc.
  • History of meningitis, meningoencephalitis, epilepsy or life-threatening allergic or immune-mediated reaction.
  • History of or current autoimmune disease or an acute episode of Guillain-Barre syndrome.
  • Patients with uncontrolled bleeding diathesis and/or on concomitant treatment with coumarin anticoagulant.
  • Presence of any unstable medical or psychiatric condition (defined by the Diagnostic and Statistical Manual of Mental Disorders-IV [DSM-IV]) that could reasonably have been expected to subject the patient to unwarranted risk from participation in the study or result in a significant deterioration of the patient's clinical course.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/ml).
  • Hemoglobin levels below 8.0 g/dl and/or patients who required greater than 10 (ten) blood transfusions since the acute injury
  • Patients with concomitant treatment with Metamizole from Screening until end of Follow Up phase
  • Mechanical ventilation will be allowed for patients in Cohort 5, the patient must not depend completely on the ventilation but should show some degree of spontaneous ventilation. Only those modes of ventilation where the patient must initiate all breaths are allowed (e.g. continuous positive airway pressure [CPAP]).

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406016

Locations
Canada
Novartis Investigative site
Calgary, Canada
Novartis Investigative site
Montreal, Canada
Novartis Investigative site
Toronto, Canada
Novartis Investigative site
Vancouver, Canada
Germany
Novartis Investigative site
Bad Wildungen, Germany, 34537
Novartis Investigative site
Bayreuth, Germany, 09445
Novartis Investigative site
Bochum, Germany, 44789
Novartis Investigative site
Hamburg, Germany, 21033
Novartis Investigative site
Heidelberg, Germany, 69118
Novartis Investigative site
Karlsbad-Lagensteinbach, Germany, 76307
Novartis Investigative site
Murnau, Germany, 82418
Novartis Investigative site
Tuebingen, Germany, 72076
Novartis Investigative site
Ulm, Germany, 89081
Switzerland
Novartis Investigative Site
Zuerich, Switzerland, 8008
Novartis Investigative site
Zurich, Switzerland, 8008
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00406016     History of Changes
Other Study ID Numbers: CATI355A2102
Study First Received: November 30, 2006
Last Updated: November 2, 2011
Health Authority: Germany: Paul-Ehrlich-Institut
Switzerland: Swissmedic
Canada: Biologics and Genetic Therapies Directorate.
United States: Food and Drug Administration

Keywords provided by Novartis:
Acute spinal cord injury;

Additional relevant MeSH terms:
Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System

ClinicalTrials.gov processed this record on August 27, 2014