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

Primary Purpose

Amyotrophic Lateral Sclerosis (ALS)

Status

Unknown status

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Anakinra

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis (ALS) focused on measuring ALS, Anakinra, Kineret, Progressive Muscular Atrophy, PMA, Safety Trial, Tolerability Trial

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Charité University HospitalRecruiting

Outcomes

Primary Outcome Measures

Number and Severity of adverse events (AE)

Number and Severity of serious adverse events (SAE)

Number and Severity of adverse drug reactions (ARD)

Number and Severity of unexpected adverse drug reactions (UADR)

Number and Severity of serious adverse drug reactions (SADR)

Number and Severity of suspected unexpected serious adverse reaction (SUSAR)

Pathological laboratory parameters

Secondary Outcome Measures

Long Term Tolerability and Safety of Anakinra in ALS Patients

Full Information

NCT ID

NCT01277315

First Posted

January 13, 2011

Last Updated

February 25, 2011

Sponsor

Charite University, Berlin, Germany

Collaborators

Max Planck Institute for Infection Biology

1. Study Identification

Unique Protocol Identification Number

NCT01277315

Brief Title

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

2. Study Status

Record Verification Date

January 2011

Overall Recruitment Status

Unknown status

Study Start Date

February 2011 (undefined)

Primary Completion Date

June 2012 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Charite University, Berlin, Germany

Collaborators

Max Planck Institute for Infection Biology

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis (ALS)

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Anakinra

Intervention Description

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

Primary Outcome Measure Information:

Title

Number and Severity of adverse events (AE)

Time Frame

1 month

Title

Number and Severity of serious adverse events (SAE)

Time Frame

1 month

Title

Number and Severity of adverse drug reactions (ARD)

Time Frame

1 month

Title

Number and Severity of unexpected adverse drug reactions (UADR)

Time Frame

1 month

Title

Number and Severity of serious adverse drug reactions (SADR)

Time Frame

1 month

Title

Number and Severity of suspected unexpected serious adverse reaction (SUSAR)

Time Frame

1 month

Title

Pathological laboratory parameters

Time Frame

1 month

Secondary Outcome Measure Information:

Title

Long Term Tolerability and Safety of Anakinra in ALS Patients

Time Frame

1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Thomas Meyer, MD

Phone

+49.30.450660032

thomas.meyer@charite.de

First Name & Middle Initial & Last Name or Official Title & Degree

Teresa Holm, MD

Phone

+49.30.450660218

teresa.holm@charite.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Meyer, MD

Organizational Affiliation

Charité University Hospital, Berlin, Germany

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charité University Hospital

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thomas Meyer, MD

Phone

+49.30.450660032

thomas.meyer@charite.de

First Name & Middle Initial & Last Name & Degree

Teresa Holm, MD

Phone

+49.30.450660218

teresa.holm@charite.de

12. IPD Sharing Statement

Citations:

PubMed Identifier

26444282

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.

Results Reference

derived

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

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