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

Study Overview
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Brief Summary
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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.

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

Official Title
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Open Safety and Tolerability Trial to Evaluate a Subcutaneous Injection Solution of 100 mg of Anakinra in Combination With Riluzol in Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Drug: Anakinra


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

| Intervention/Treatment |
| --- |
|Drug: Anakinra|Open Safety and Tolerability study to evaluate a subcutaneous application 100 mg of Anakinra in combination with Riluzol in Amyotrophic Lateral Sclerosis.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Severity of adverse events (AE) |  | 1 month | 
| Number and Severity of serious adverse events (SAE) |  | 1 month | 
| Number and Severity of adverse drug reactions (ARD) |  | 1 month | 
| Number and Severity of unexpected adverse drug reactions (UADR) |  | 1 month | 
| Number and Severity of serious adverse drug reactions (SADR) |  | 1 month | 
| Number and Severity of suspected unexpected serious adverse reaction (SUSAR) |  | 1 month | 
| Pathological laboratory parameters |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long Term Tolerability and Safety of Anakinra in ALS Patients |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Anakinra, Kineret, Progressive Muscular Atrophy, PMA, Safety Trial, Tolerability Trial