A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
- Registration Number
- NCT00561366
- Lead Sponsor
- CytRx
- Brief 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.
- Detailed 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 & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
-
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:
- Substance abuse within the past year
- Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease
- AIDS or AIDS-related complex
- 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.
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Female volunteers who are breast-feeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Placebo - 2 Arimoclomol -
- Primary Outcome Measures
Name Time Method ALSFRS-R 9 months
- Secondary Outcome Measures
Name Time Method ALSFRS-R 18 months Survival 18 months Muscle strength 9 and 18 months Pulmonary function 9 and 18 months MUNE 9 and 18 months Quality of Life 9 and 18 months
Trial Locations
- Locations (35)
Virginia Mason Clinic - Tier 2 Site
๐บ๐ธSeattle, Washington, United States
Massachusetts General Hospital - Tier 1 Site
๐บ๐ธBoston, Massachusetts, United States
University of Kansas Medical Center - Tier 2 site
๐บ๐ธKansas City, Kansas, United States
Washington University - Tier 2 Site
๐บ๐ธSt. Louis, Missouri, United States
Saint Louis University, Neuromuscular Div. - Tier 2 Site
๐บ๐ธSaint Louis, Missouri, United States
Upstate Clinical Research, LLC - Tier 2 Site
๐บ๐ธAlbany, New York, United States
Emory University - Tier 2 site
๐บ๐ธAtlanta, Georgia, United States
John Hopkins University - Tier 2 Site
๐บ๐ธBaltimore, Maryland, United States
University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site
๐จ๐ฆToronto, Ontario, Canada
University of Pittsburgh Medical Center - Tier 2 Site
๐บ๐ธPittsburgh, Pennsylvania, United States
Columbia University Medical Center - Tier 2 site
๐บ๐ธNew York, New York, United States
Pennsylvania State University School of Medicine - Tier 2 Site
๐บ๐ธHershey, Pennsylvania, United States
University of California Los Angeles - Tier 2 Site
๐บ๐ธPacific Palisades, California, United States
Northwestern University, Dept. of Neurology - Tier 2 Site
๐บ๐ธChicago, Illinois, United States
Baystate Medical Center - Tier 2 Site
๐บ๐ธSpringfield, Massachusetts, United States
University of Miami - Tier 2 Site
๐บ๐ธMiami, Florida, United States
Mount Sinai School of Medicine - Tier 2 Site
๐บ๐ธNew York, New York, United States
Cleveland Clinic Foundation -Tier 2 site
๐บ๐ธCleveland, Ohio, United States
Wake Forest University School of Medicine -Tier 2 Site
๐บ๐ธWinston Salem, North Carolina, United States
Medical College of Wisconsin - Tier 2 Site
๐บ๐ธMilwaukee, Wisconsin, United States
University of California - San Francisco - Tier 2 Site
๐บ๐ธSan Francisco, California, United States
University of Colorado Health Sciences Center - Tier 2 Site
๐บ๐ธDenver, Colorado, United States
Duke University Medical Center - Tier 1 Site
๐บ๐ธDurham, North Carolina, United States
Providence ALS Center - Tier 2 Site
๐บ๐ธPortland, Oregon, United States
University of Texas Health Science Center - Tier 2 Site
๐บ๐ธSan Antonio, Texas, United States
SUNY Downstate Medical Center - Tier 1 Site
๐บ๐ธSyracuse, New York, United States
Drexel University College of Medicine - Tier 1 Site
๐บ๐ธPhiladelphia, Pennsylvania, United States
University of Virginia - Tier 2 Sites
๐บ๐ธCharlottesville, Virginia, United States
Texas Neurology, PA - Tier 2 Site
๐บ๐ธDallas, Texas, United States
London Health Science Center - Tier 2 Site
๐จ๐ฆLondon, Ontario, Canada
BryanLGH Medical Center - Tier 2 Site
๐บ๐ธLincoln, Nebraska, United States
Vanderbilt University Medical Center - Tier 2
๐บ๐ธNashville, Tennessee, United States
University of Vermont, College of Medicine - Tier 2
๐บ๐ธBurlington, Vermont, United States
University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site
๐จ๐ฆVancouver, British Columbia, Canada
Montreal Neurological Institute - Tier 2
๐จ๐ฆMontreal, Quebec, Canada