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Safety and Tolerability of Anakinra in Combination With Riluzol in Amyotrophic Lateral Sclerosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Charite University, Berlin, Germany.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Max Planck Institute for Infection Biology
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01277315
First received: January 13, 2011
Last updated: February 25, 2011
Last verified: January 2011
History of Changes
  Purpose

Amyotrophic Lateral Sclerosis (ALS) is an adult neurodegenerative disease that is caused by a selective degeneration of the motor nerve cells in the cortex and myelon. As a result of motor neurodegeneration, a progredient paralysis of the extremities and of the speaking, swallowing, and breathing musculature develops. ALS leads to death by respiratory insufficiency in a mean course of 3-5 years. So far, Riluzole is the only approved neuroprotective medication which effects a slight lifespan prolongation of 1.5 - 2.5 months. Riluzole inhibits the presynaptic glutamate release and lowers the level of glutamate liberated by activated microglia.

The researchers propose an investigational therapy of ALS with subcutaneous administration of 100 mg of Anakinra. The neuronal inflammation is a crucial pathogenetic factor of the motor neuron degeneration. Inflammatory processes are detectable in sporadic ALS, in the autosomal-dominant form of ALS and in transgenic mouse model. The rationale of this clinical trial is based on the anti-inflammatory effect of Anakinra. One of the key mediators of inflammatory response is Interleukin-1. Anakinra is a recombinant produced Interleukin-1 receptor antagonist. This gives Anakinra anti-inflammatory attributes that presumably reduce motor neuron degeneration and disease progression.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis (ALS)
 Drug: Anakinra
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Safety and Tolerability Trial to Evaluate a Subcutaneous Injection Solution of 100 mg of Anakinra in Combination With Riluzol in Amyotrophic Lateral Sclerosis

Resource links provided by NLM:

Drug Information available for: Anakinra
U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Number and Severity of adverse events (AE) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number and Severity of serious adverse events (SAE) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number and Severity of adverse drug reactions (ARD) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number and Severity of unexpected adverse drug reactions (UADR) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number and Severity of serious adverse drug reactions (SADR) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Number and Severity of suspected unexpected serious adverse reaction (SUSAR) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Pathological laboratory parameters [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Long Term Tolerability and Safety of Anakinra in ALS Patients [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: February 2011
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Anakinra
    Open Safety and Tolerability study to evaluate a subcutaneous application 100 mg of Anakinra in combination with Riluzol in Amyotrophic Lateral Sclerosis.
Detailed Description:

Open Safety and Tolerability study to evaluate a subcutaneous application 100 mg of Anakinra in combination with Riluzol in Amyotrophic Lateral Sclerosis.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients between 18 and 80 years of age
  • Clinical diagnosis of amyotrophic lateral sclerosis with predominant affection of the lower motor neuron or the clinical ALS variant of progressive muscular atrophy (PMA)
  • Clinical signs of lower motor neuron degeneration in at least one anatomic region beyond the brain stem
  • Sporadic and familial ALS
  • Onset of paresis six months to four years before study inclusion
  • Treatment with riluzol 100mg/d at least 1 month before study inclusion

Exclusion Criteria:

  • Diagnosis of amyotrophic lateral sclerosis with predominant affection or the upper motor neuron without clinical signs of a concurrent affection of the lower motor neuron in at least one anatomic region beyond the brain stem (spastic ALS) - Diagnosis of primary lateral sclerosis (PLS)
  • Patients with known intolerance to anakinra, riluzol or one of the additives
  • Clinically severe hypoventilation syndrome with vital capacity < 50%
  • Pregnancy or breastfeeding
  • Continuous non-invasive ventilation with ventilator-free time < 2 hours - Tracheotomy and mechanical ventilation
  • Laboratory parameters outside the normal range that correspond to a clinically severe cardiovascular, pulmological, hematological, hepatological, metabolic or renal disease
  • Malignancies
  • Severe renal insufficiency (creatinine clearance < 30 ml/min)
  • History of recurrent infections or a disease that may predispose to infections
  • Severe neutropenia (absolute neutrophil count < 1.5 x 109/l)
  • Monoclonal gammopathy of unknown significance
  • Infections including infections with HIV and hepatitis B and C
  • Dementia and unable to give informed consent
  • History of epilepsy and epileptic seizures
  • Contraindication to E coli-derived proteins, anakinra or any components of the product
  • Concurrent therapy of anakinra and etanercept or other TNF blocking agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01277315

Contacts
Contact: Thomas Meyer, MD +49.30.450660032 thomas.meyer@charite.de
Contact: Teresa Holm, MD +49.30.450660218 teresa.holm@charite.de

Locations
Germany
Charité University Hospital Recruiting
Berlin, Germany, 13353
Contact: Thomas Meyer, MD     +49.30.450660032     thomas.meyer@charite.de    
Contact: Teresa Holm, MD     +49.30.450660218     teresa.holm@charite.de    
Sponsors and Collaborators
Charite University, Berlin, Germany
Max Planck Institute for Infection Biology
Investigators
Principal Investigator: Thomas Meyer, MD Charité University Hospital, Berlin, Germany
  More Information

No publications provided

Responsible Party: Charité University, Berlin, Germany, Charité Universitätsmedizin, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01277315     History of Changes
Other Study ID Numbers: ANA-ALS01
Study First Received: January 13, 2011
Last Updated: February 25, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
ALS
Anakinra
Kineret
Progressive Muscular Atrophy
 PMA
Safety Trial
Tolerability Trial

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
 Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013