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

This study has been withdrawn prior to enrollment.
(Not moving forward with program.)
Sponsor:
Information provided by (Responsible Party):
CytRx
ClinicalTrials.gov Identifier:
NCT00561366
First received: November 16, 2007
Last updated: February 8, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Placebo
Drug: Arimoclomol
Phase 2

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

Resource links provided by NLM:


Further study details as provided by CytRx:

Primary Outcome Measures:
  • ALSFRS-R [ Time Frame: 9 months ]

Secondary Outcome Measures:
  • ALSFRS-R [ Time Frame: 18 months ]
  • Survival [ Time Frame: 18 months ]
  • Muscle strength [ Time Frame: 9 and 18 months ]
  • Pulmonary function [ Time Frame: 9 and 18 months ]
  • MUNE [ Time Frame: 9 and 18 months ]
  • Quality of Life [ Time Frame: 9 and 18 months ]

Enrollment: 0
Arms Assigned Interventions
Placebo Comparator: 1 Drug: Placebo
Placebo t.i.d.
Experimental: 2 Drug: Arimoclomol
capsule, 400 mg t.i.d.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561366

  Hide Study Locations
Locations
United States, California
University of California Los Angeles - Tier 2 Site
Pacific Palisades, California, United States, 90272
University of California - San Francisco - Tier 2 Site
San Francisco, California, United States, 94117
United States, Colorado
University of Colorado Health Sciences Center - Tier 2 Site
Denver, Colorado, United States, 80262
United States, Florida
University of Miami - Tier 2 Site
Miami, Florida, United States, 33136
United States, Georgia
Emory University - Tier 2 site
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University, Dept. of Neurology - Tier 2 Site
Chicago, Illinois, United States, 60611
United States, Kansas
University of Kansas Medical Center - Tier 2 site
Kansas City, Kansas, United States, 66160
United States, Maryland
John Hopkins University - Tier 2 Site
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital - Tier 1 Site
Boston, Massachusetts, United States, 02114
Baystate Medical Center - Tier 2 Site
Springfield, Massachusetts, United States, 01199
United States, Missouri
Saint Louis University, Neuromuscular Div. - Tier 2 Site
Saint Louis, Missouri, United States, 63110
Washington University - Tier 2 Site
St. Louis, Missouri, United States, 63110
United States, Nebraska
BryanLGH Medical Center - Tier 2 Site
Lincoln, Nebraska, United States, 68506
United States, New York
Upstate Clinical Research, LLC - Tier 2 Site
Albany, New York, United States, 12205
Mount Sinai School of Medicine - Tier 2 Site
New York, New York, United States, 10029
Columbia University Medical Center - Tier 2 site
New York, New York, United States, 10032
SUNY Downstate Medical Center - Tier 1 Site
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center - Tier 1 Site
Durham, North Carolina, United States, 27705
Wake Forest University School of Medicine -Tier 2 Site
Winston Salem, North Carolina, United States, 27157
United States, Ohio
Cleveland Clinic Foundation -Tier 2 site
Cleveland, Ohio, United States, 44195
United States, Oregon
Providence ALS Center - Tier 2 Site
Portland, Oregon, United States, 97213
United States, Pennsylvania
Pennsylvania State University School of Medicine - Tier 2 Site
Hershey, Pennsylvania, United States, 17033
Drexel University College of Medicine - Tier 1 Site
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Medical Center - Tier 2 Site
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center - Tier 2
Nashville, Tennessee, United States, 37232-2551
United States, Texas
Texas Neurology, PA - Tier 2 Site
Dallas, Texas, United States, 75214
University of Texas Health Science Center - Tier 2 Site
San Antonio, Texas, United States, 78229-3900
United States, Vermont
University of Vermont, College of Medicine - Tier 2
Burlington, Vermont, United States, 05405
United States, Virginia
University of Virginia - Tier 2 Sites
Charlottesville, Virginia, United States, 22908
United States, Washington
Virginia Mason Clinic - Tier 2 Site
Seattle, Washington, United States, 98101
United States, Wisconsin
Medical College of Wisconsin - Tier 2 Site
Milwaukee, Wisconsin, United States, 53226
Canada, British Columbia
University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site
Vancouver, British Columbia, Canada, V5Z 2G9
Canada, Ontario
London Health Science Center - Tier 2 Site
London, Ontario, Canada, N6A 5A5
University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Montreal Neurological Institute - Tier 2
Montreal, Quebec, Canada, H3A 2B4
Sponsors and Collaborators
CytRx
Investigators
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
Principal Investigator: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
  More Information

No publications provided

Responsible Party: CytRx
ClinicalTrials.gov Identifier: NCT00561366     History of Changes
Other Study ID Numbers: AALS-003
Study First Received: November 16, 2007
Last Updated: February 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by CytRx:
ALS
Lou Gehrig's disease

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014