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

Charité University Medicine Berlin

Status and phase

Completed

Phase 2

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Treatments

Drug: Anakinra

Study type

Interventional

Funder types

Other

Identifiers

NCT01277315

ANA-ALS01

Details and patient eligibility

About

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.

Full description

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

Enrollment

20 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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