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

• ClinicalTrials.gov Identifier: NCT00244244
• Recruitment Status: Completed
• First Posted: October 26, 2005
• Last Update Posted: February 9, 2012
• Sponsor: CytRx
• Information provided by (Responsible Party): CytRx

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: arimoclomol	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)
• Study Start Date: October 2005
• Actual Primary Completion Date: January 2007
• Actual Study Completion Date: January 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Safety

Secondary Outcome Measures :

1. Pharmacokinetics
2. ALSFRS-R
3. Vital Capacity

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, Irvine Medical Center

Irvine, California, United States, 92868

United States, Florida

University of Miami School of Medicine

Miami, Florida, United States, 33136

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02129

United States, Minnesota

Hennepin Faculty Associates/Berman Center

Minneapolis, Minnesota, United States, 55404

United States, New York

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27705

United States, Pennsylvania

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

CytRx

Investigators

• Principal Investigator: Merit Cudkowicz, MD; Massachusetts General Hospital
• Principal Investigator: Jeremy Shefner, MD; State University of New York - Upstate Medical University

More Information

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.

• Responsible Party: CytRx
• ClinicalTrials.gov Identifier: NCT00244244
• Other Study ID Numbers: AALS-001
• First Posted: October 26, 2005
• Last Update Posted: February 9, 2012
• Last Verified: February 2012

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases