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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This study has been withdrawn prior to enrollment.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

November 16, 2007
February 8, 2012
Not Provided
Not Provided
ALSFRS-R [ Time Frame: 9 months ]
Same as current
Complete list of historical versions of study NCT00561366 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
A Multicenter, Double-Blind Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With ALS
A Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Investigate the Safety and Efficacy of Arimoclomol in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Amyotrophic Lateral Sclerosis
  • Drug: Placebo
    Placebo t.i.d.
  • Drug: Arimoclomol
    capsule, 400 mg t.i.d.
  • Placebo Comparator: 1
    Intervention: Drug: Placebo
  • Experimental: 2
    Intervention: Drug: Arimoclomol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
Not Provided
Not Provided

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00561366
AALS-003
Yes
CytRx
CytRx
Not Provided
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
Principal Investigator: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
CytRx
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP