A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

A Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00561366
• Other study ID #: AALS-003
• Status: Withdrawn
• Phase: Phase 2
• First received: November 16, 2007
• Last updated: February 8, 2012

Study information

• Verified date: February 2012
• Source: CytRx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a Phase 2b double-blind, randomized, placebo-controlled parallel-group study evaluating the safety and efficacy of arimoclomol (400 mg t.i.d.) compared to placebo. A safety lead-in phase will be employed to ensure the safety of all study volunteers.

Tier I (Safety Lead-in): During the enrollment period for the safety lead-in phase, 24 volunteers meeting inclusion/exclusion criteria will be randomized at 4 investigative sites. These volunteers will have weekly visits during the first 4 weeks after starting treatment. Pharmacokinetics (PK) will be performed at various timepoints throughout these 4 weeks. After the initial 4 weeks of treatment, visits will continue at 4-week intervals up to Week 36, subsequently visits will occur every 8 weeks up to Week 68. A final visit will occur at Week 72. There will be a 28-day post study medication Follow-Up Telephone Call to assess medical status and adverse events.

Tier II: After the Tier I volunteers finish 4 weeks of treatment, their data will be reviewed by the IDMC and, if no serious safety issues are identified, the recommendation will be made to start the second enrollment period (Tier II). During Tier II enrollment, volunteers recruited from approximately 30 to 40 centers in the US and Canada will be randomized. After screening and randomization, volunteers will be followed every 4 weeks for 9 months. Subsequently visits will occur every 8 weeks up to Week 68, with interim Follow-Up Telephone Calls at Weeks 16, 24, and 32 and a final visit at Week 72. A Week 76 Follow-Up Telephone Call to assess medical status and adverse events will occur at 28 days post last dose of study medication.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Familial or sporadic ALS.

• Diagnosed with laboratory-supported probable, probable or definite ALS according to the World Federation of Neurology El Escorial criteria for less than or equal to 36 months' duration prior to the Screening Visit.

• Vital capacity (VC) equal to or greater than 70% predicted value for gender, height and age at the Screening Visit.

• Geographic accessibility to the study site.

• Ability to take oral medication at the Screening Visit, based on verbal report.

• Fluency in English, Spanish or Canadian French.

Exclusion Criteria:

• History of known sensitivity or intolerability to arimoclomol or to any other related compound.

• Prior exposure to arimoclomol through a clinical trial or physician-sponsored IND.

• Exposure to any investigational agent within 30 days of the Screening Visit.

• Presence of any of the following clinical conditions:

1. Substance abuse within the past year

2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease

3. AIDS or AIDS-related complex

4. Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the Screening Visit.

• Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, creatinine clearance less than 70 cc/min, alanine aminotransferase (ALT) greater than 3.0 times the upper limit of normal, total bilirubin greater than 1.5 times the upper limit of normal, white blood cell (WBC) count less than 3,500/mm3, platelet concentration of <100,000/ul, hematocrit level of less than 33 % for female or less than 35 % for male, or coagulation tests (PT, PTT) greater than or equal to 1.5 times upper limit of normal.

• Female volunteers who are breast-feeding.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Placebo
Placebo t.i.d.
• Arimoclomol
capsule, 400 mg t.i.d.

Locations

Country	Name	City	State
Canada	London Health Science Center - Tier 2 Site	London	Ontario
Canada	Montreal Neurological Institute - Tier 2	Montreal	Quebec
Canada	University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site	Toronto	Ontario
Canada	University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site	Vancouver	British Columbia
United States	Upstate Clinical Research, LLC - Tier 2 Site	Albany	New York
United States	Emory University - Tier 2 site	Atlanta	Georgia
United States	John Hopkins University - Tier 2 Site	Baltimore	Maryland
United States	Massachusetts General Hospital - Tier 1 Site	Boston	Massachusetts
United States	University of Vermont, College of Medicine - Tier 2	Burlington	Vermont
United States	University of Virginia - Tier 2 Sites	Charlottesville	Virginia
United States	Northwestern University, Dept. of Neurology - Tier 2 Site	Chicago	Illinois
United States	Cleveland Clinic Foundation -Tier 2 site	Cleveland	Ohio
United States	Texas Neurology, PA - Tier 2 Site	Dallas	Texas
United States	University of Colorado Health Sciences Center - Tier 2 Site	Denver	Colorado
United States	Duke University Medical Center - Tier 1 Site	Durham	North Carolina
United States	Pennsylvania State University School of Medicine - Tier 2 Site	Hershey	Pennsylvania
United States	University of Kansas Medical Center - Tier 2 site	Kansas City	Kansas
United States	BryanLGH Medical Center - Tier 2 Site	Lincoln	Nebraska
United States	University of Miami - Tier 2 Site	Miami	Florida
United States	Medical College of Wisconsin - Tier 2 Site	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center - Tier 2	Nashville	Tennessee
United States	Columbia University Medical Center - Tier 2 site	New York	New York
United States	Mount Sinai School of Medicine - Tier 2 Site	New York	New York
United States	University of California Los Angeles - Tier 2 Site	Pacific Palisades	California
United States	Drexel University College of Medicine - Tier 1 Site	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center - Tier 2 Site	Pittsburgh	Pennsylvania
United States	Providence ALS Center - Tier 2 Site	Portland	Oregon
United States	Saint Louis University, Neuromuscular Div. - Tier 2 Site	Saint Louis	Missouri
United States	University of Texas Health Science Center - Tier 2 Site	San Antonio	Texas
United States	University of California - San Francisco - Tier 2 Site	San Francisco	California
United States	Virginia Mason Clinic - Tier 2 Site	Seattle	Washington
United States	Baystate Medical Center - Tier 2 Site	Springfield	Massachusetts
United States	Washington University - Tier 2 Site	St. Louis	Missouri
United States	SUNY Downstate Medical Center - Tier 1 Site	Syracuse	New York
United States	Wake Forest University School of Medicine -Tier 2 Site	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
CytRx

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ALSFRS-R		9 months
Secondary	ALSFRS-R		18 months
Secondary	Survival		18 months
Secondary	Muscle strength		9 and 18 months
Secondary	Pulmonary function		9 and 18 months
Secondary	MUNE		9 and 18 months
Secondary	Quality of Life		9 and 18 months