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

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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: Anakinra

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charite University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Max Planck Institute for Infection Biology
• Investigators: Principal Investigator: Thomas Meyer, MD, Charité University Hospital, Berlin, Germany

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: January 13, 2011
• First Submitted That Met QC Criteria: January 13, 2011
• First Posted (Estimated): January 14, 2011

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ALS; Kineret; Anakinra; Progressive Muscular Atrophy; PMA; Safety Trial; Tolerability Trial
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: ANA-ALS01