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

NCT ID: NCT00561366

Last Updated: 2012-02-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Brief Summary

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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

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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.

Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo t.i.d.

2

Group Type EXPERIMENTAL

Arimoclomol

Intervention Type DRUG

capsule, 400 mg t.i.d.

Interventions

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Placebo

Placebo t.i.d.

Intervention Type DRUG

Arimoclomol

capsule, 400 mg t.i.d.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CytRx

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Merit Cudkowicz, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Jeremy Shefner, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State University of New York - Upstate Medical University

Locations

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University of California Los Angeles - Tier 2 Site

Pacific Palisades, California, United States

Site Status

University of California - San Francisco - Tier 2 Site

San Francisco, California, United States

Site Status

University of Colorado Health Sciences Center - Tier 2 Site

Denver, Colorado, United States

Site Status

University of Miami - Tier 2 Site

Miami, Florida, United States

Site Status

Emory University - Tier 2 site

Atlanta, Georgia, United States

Site Status

Northwestern University, Dept. of Neurology - Tier 2 Site

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center - Tier 2 site

Kansas City, Kansas, United States

Site Status

John Hopkins University - Tier 2 Site

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital - Tier 1 Site

Boston, Massachusetts, United States

Site Status

Baystate Medical Center - Tier 2 Site

Springfield, Massachusetts, United States

Site Status

Saint Louis University, Neuromuscular Div. - Tier 2 Site

St Louis, Missouri, United States

Site Status

Washington University - Tier 2 Site

St Louis, Missouri, United States

Site Status

BryanLGH Medical Center - Tier 2 Site

Lincoln, Nebraska, United States

Site Status

Upstate Clinical Research, LLC - Tier 2 Site

Albany, New York, United States

Site Status

Mount Sinai School of Medicine - Tier 2 Site

New York, New York, United States

Site Status

Columbia University Medical Center - Tier 2 site

New York, New York, United States

Site Status

SUNY Downstate Medical Center - Tier 1 Site

Syracuse, New York, United States

Site Status

Duke University Medical Center - Tier 1 Site

Durham, North Carolina, United States

Site Status

Wake Forest University School of Medicine -Tier 2 Site

Winston-Salem, North Carolina, United States

Site Status

Cleveland Clinic Foundation -Tier 2 site

Cleveland, Ohio, United States

Site Status

Providence ALS Center - Tier 2 Site

Portland, Oregon, United States

Site Status

Pennsylvania State University School of Medicine - Tier 2 Site

Hershey, Pennsylvania, United States

Site Status

Drexel University College of Medicine - Tier 1 Site

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center - Tier 2 Site

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center - Tier 2

Nashville, Tennessee, United States

Site Status

Texas Neurology, PA - Tier 2 Site

Dallas, Texas, United States

Site Status

University of Texas Health Science Center - Tier 2 Site

San Antonio, Texas, United States

Site Status

University of Vermont, College of Medicine - Tier 2

Burlington, Vermont, United States

Site Status

University of Virginia - Tier 2 Sites

Charlottesville, Virginia, United States

Site Status

Virginia Mason Clinic - Tier 2 Site

Seattle, Washington, United States

Site Status

Medical College of Wisconsin - Tier 2 Site

Milwaukee, Wisconsin, United States

Site Status

University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site

Vancouver, British Columbia, Canada

Site Status

London Health Science Center - Tier 2 Site

London, Ontario, Canada

Site Status

University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site

Toronto, Ontario, Canada

Site Status

Montreal Neurological Institute - Tier 2

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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AALS-003

Identifier Type: -

Identifier Source: org_study_id

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