A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in ALS

A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)

The primary purpose of this study is to evaluate the safety and tolerability of arimoclomol in ALS patients following 90 days of dosing. In addition, the amount of arimoclomol in blood and cerebrospinal fluid will be measured.

Study Overview

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

Detailed Description

Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease onset in a mutant superoxide dismutase (SOD1) transgenic mouse model of ALS. Furthermore, it has been demonstrated to have neuroprotective and neuroregenerative effects in other rat models of nerve damage. Molecular chaperone proteins are critical in the cellular response to stress and protein misfolding. Recent data suggest that the SOD1 mutation responsible for ALS in some patients with familial disease reduces the availability of a variety of molecular chaperones, and thus weakens their ability to respond to cellular stress. Protein misfolding and consequent aggregation may play a role in the pathogenesis of both the familial and sporadic forms of ALS. Therapeutic agents such as arimoclomol that improve cellular chaperone response to protein misfolding may be helpful in ALS.

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92868
      • University of California, Irvine Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Hennepin Faculty Associates/Berman Center
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Drexel University College of Medicine
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Familial or sporadic ALS
• Vital capacity equal to or more than 60% predicted value for gender, height and age at the screening visit
• First ALS symptoms occurred no more than five years prior to screening
• Must be able to take oral medication

Exclusion Criteria:

• Dependence on mechanical ventilation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety

Secondary Outcome Measures

Outcome Measure
Pharmacokinetics
ALSFRS-R
Vital Capacity

Collaborators and Investigators

• Sponsor: CytRx
• Investigators: Principal Investigator: Jeremy Shefner, MD, State University of New York - Upstate Medical University

Publications and helpful links

General Publications

• Kieran D, Kalmar B, Dick JR, Riddoch-Contreras J, Burnstock G, Greensmith L. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat Med. 2004 Apr;10(4):402-5. doi: 10.1038/nm1021. Epub 2004 Mar 21.
• Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. doi: 10.1038/nm0404-345. No abstract available.
• Kurthy M, Mogyorosi T, Nagy K, Kukorelli T, Jednakovits A, Talosi L, Biro K. Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci. 2002 Jun;967:482-9. doi: 10.1111/j.1749-6632.2002.tb04306.x.
• Kalmar B, Burnstock G, Vrbova G, Urbanics R, Csermely P, Greensmith L. Upregulation of heat shock proteins rescues motoneurones from axotomy-induced cell death in neonatal rats. Exp Neurol. 2002 Jul;176(1):87-97. doi: 10.1006/exnr.2002.7945.
• Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. doi: 10.1038/nrn1587.
• Kalmar B, Greensmith L, Malcangio M, McMahon SB, Csermely P, Burnstock G. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury. Exp Neurol. 2003 Dec;184(2):636-47. doi: 10.1016/S0014-4886(03)00343-1.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 26, 2005

Study Record Updates

• Last Update Posted (Estimate): February 9, 2012
• Last Update Submitted That Met QC Criteria: February 8, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• 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
• Other Study ID Numbers: AALS-001