Back to resultsA Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Arimoclomol
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Lou Gehrig's disease
Eligibility Criteria
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:
- 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.
- Female volunteers who are breast-feeding.
Sites / Locations
- University of California Los Angeles - Tier 2 Site
- University of California - San Francisco - Tier 2 Site
- University of Colorado Health Sciences Center - Tier 2 Site
- University of Miami - Tier 2 Site
- Emory University - Tier 2 site
- Northwestern University, Dept. of Neurology - Tier 2 Site
- University of Kansas Medical Center - Tier 2 site
- John Hopkins University - Tier 2 Site
- Massachusetts General Hospital - Tier 1 Site
- Baystate Medical Center - Tier 2 Site
- Saint Louis University, Neuromuscular Div. - Tier 2 Site
- Washington University - Tier 2 Site
- BryanLGH Medical Center - Tier 2 Site
- Upstate Clinical Research, LLC - Tier 2 Site
- Mount Sinai School of Medicine - Tier 2 Site
- Columbia University Medical Center - Tier 2 site
- SUNY Downstate Medical Center - Tier 1 Site
- Duke University Medical Center - Tier 1 Site
- Wake Forest University School of Medicine -Tier 2 Site
- Cleveland Clinic Foundation -Tier 2 site
- Providence ALS Center - Tier 2 Site
- Pennsylvania State University School of Medicine - Tier 2 Site
- Drexel University College of Medicine - Tier 1 Site
- University of Pittsburgh Medical Center - Tier 2 Site
- Vanderbilt University Medical Center - Tier 2
- Texas Neurology, PA - Tier 2 Site
- University of Texas Health Science Center - Tier 2 Site
- University of Vermont, College of Medicine - Tier 2
- University of Virginia - Tier 2 Sites
- Virginia Mason Clinic - Tier 2 Site
- Medical College of Wisconsin - Tier 2 Site
- University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site
- London Health Science Center - Tier 2 Site
- University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site
- Montreal Neurological Institute - Tier 2
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
1
2
Arm Description
Outcomes
Primary Outcome Measures
ALSFRS-R
Secondary Outcome Measures
ALSFRS-R
Survival
Muscle strength
Pulmonary function
MUNE
Quality of Life
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00561366
Brief Title
A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
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)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Not moving forward with program.
Study Start Date
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Primary Completion Date
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Study Completion Date
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3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CytRx
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS, Lou Gehrig's disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Placebo Comparator
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo t.i.d.
Intervention Type
Drug
Intervention Name(s)
Arimoclomol
Intervention Description
capsule, 400 mg t.i.d.
Primary Outcome Measure Information:
Title
ALSFRS-R
Time Frame
9 months
Secondary Outcome Measure Information:
Title
ALSFRS-R
Time Frame
18 months
Title
Survival
Time Frame
18 months
Title
Muscle strength
Time Frame
9 and 18 months
Title
Pulmonary function
Time Frame
9 and 18 months
Title
MUNE
Time Frame
9 and 18 months
Title
Quality of Life
Time Frame
9 and 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
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.
Female volunteers who are breast-feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merit Cudkowicz, MD, MSc
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeremy Shefner, MD, PhD
Organizational Affiliation
State University of New York - Upstate Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Los Angeles - Tier 2 Site
City
Pacific Palisades
State/Province
California
ZIP/Postal Code
90272
Country
United States
Facility Name
University of California - San Francisco - Tier 2 Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
University of Colorado Health Sciences Center - Tier 2 Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
University of Miami - Tier 2 Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory University - Tier 2 site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University, Dept. of Neurology - Tier 2 Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kansas Medical Center - Tier 2 site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
John Hopkins University - Tier 2 Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital - Tier 1 Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Baystate Medical Center - Tier 2 Site
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Saint Louis University, Neuromuscular Div. - Tier 2 Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University - Tier 2 Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
BryanLGH Medical Center - Tier 2 Site
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Facility Name
Upstate Clinical Research, LLC - Tier 2 Site
City
Albany
State/Province
New York
ZIP/Postal Code
12205
Country
United States
Facility Name
Mount Sinai School of Medicine - Tier 2 Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center - Tier 2 site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
SUNY Downstate Medical Center - Tier 1 Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Duke University Medical Center - Tier 1 Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Wake Forest University School of Medicine -Tier 2 Site
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Cleveland Clinic Foundation -Tier 2 site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Providence ALS Center - Tier 2 Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Pennsylvania State University School of Medicine - Tier 2 Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Drexel University College of Medicine - Tier 1 Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Medical Center - Tier 2 Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University Medical Center - Tier 2
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2551
Country
United States
Facility Name
Texas Neurology, PA - Tier 2 Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75214
Country
United States
Facility Name
University of Texas Health Science Center - Tier 2 Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
University of Vermont, College of Medicine - Tier 2
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
University of Virginia - Tier 2 Sites
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Virginia Mason Clinic - Tier 2 Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Medical College of Wisconsin - Tier 2 Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 2G9
Country
Canada
Facility Name
London Health Science Center - Tier 2 Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Montreal Neurological Institute - Tier 2
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
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