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

Tracking Information

• First Submitted Date: October 25, 2005
• First Posted Date: October 26, 2005
• Last Update Posted Date: February 9, 2012
• Study Start Date: October 2005
• Actual Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 25, 2005): Safety
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 25, 2005)

• Pharmacokinetics
• ALSFRS-R
• Vital Capacity

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in ALS
• Official Title: A Multicenter, Dose Ranging Safety and Pharmacokinetics Study of Arimoclomol in Amyotrophic Lateral Sclerosis (ALS)
• 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis (ALS)
• Intervention: Drug: arimoclomol
• Study Arms: Not Provided

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.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: October 25, 2005): 80
• Original Enrollment: Same as current
• Actual Study Completion Date: January 2007
• Actual Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00244244
• Other Study ID Numbers: AALS-001
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: CytRx
• Original Responsible Party: Not Provided
• Current Study Sponsor: CytRx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: CytRx
• Verification Date: February 2012