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

NCT01277315 | Completed Phase 2

• 1 other identifier: ANA-ALS01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

ALS; Anakinra; Kineret; Progressive Muscular Atrophy; PMA; Safety Trial; Tolerability Trial

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (1)

• Long Term Tolerability and Safety of Anakinra in ALS Patients

  1 month

Interventions

Anakinra DRUG

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Max Planck Institute for Infection Biology: collaborator

Study Sites (1)

Charité University Hospital

Berlin, 13353, Germany

Location

Related Publications (1)

• 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.

  PMID: 26444282 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Muscular Atrophy, Spinal

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Thomas Meyer, MD

  Charité University Hospital, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Thomas Meyer

Study Record Dates

• First Submitted: January 13, 2011
• First Posted: January 14, 2011
• Study Start: February 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

DE (1)