Clinical trial NCT01277315: Safety and Tolerability of Anakinra in Combination With Riluzol in Amyotrophic Lateral Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: ALS
Anakinra
Kineret
Progressive Muscular Atrophy
PMA
Safety Trial
Tolerability Trial
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Max Planck Institute for Infection Biology
First posted: 2011-01-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Number and Severity of adverse events (AE)
timeFrame: 1 month
measure: Number and Severity of serious adverse events (SAE)
timeFrame: 1 month
measure: Number and Severity of adverse drug reactions (ARD)
timeFrame: 1 month
measure: Number and Severity of unexpected adverse drug reactions (UADR)
timeFrame: 1 month
measure: Number and Severity of serious adverse drug reactions (SADR)
timeFrame: 1 month
measure: Number and Severity of suspected unexpected serious adverse reaction (SUSAR)
timeFrame: 1 month
measure: Pathological laboratory parameters
timeFrame: 1 month
Secondary outcomes:
measure: Long Term Tolerability and Safety of Anakinra in ALS Patients
timeFrame: 1 month
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité University Hospital
Study officials:
affiliation: Charité University Hospital, Berlin, Germany
name: Thomas Meyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maier A, Deigendesch N, Muller K, Weishaupt JH, Krannich A, Rohle R, Meissner F, Molawi K, Munch C, Holm T, Meyer R, Meyer T, Zychlinsky A. Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study. PLoS One. 2015 Oct 7;10(10):e0139684. doi: 10.1371/journal.pone.0139684. eCollection 2015.