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

Sponsor
CytRx (Industry)
Overall Status
Withdrawn
CT.gov ID
NCT00561366
Collaborator
(none)
0
Enrollment
35
Locations
2
Arms
0
Patients Per Site

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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)

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: 1

Drug: Placebo
Placebo t.i.d.
Experimental: 2

Drug: Arimoclomol
capsule, 400 mg t.i.d.

Outcome Measures

Primary Outcome Measures

  1. ALSFRS-R [9 months]

Secondary Outcome Measures

  1. ALSFRS-R [18 months]

  2. Survival [18 months]

  3. Muscle strength [9 and 18 months]

  4. Pulmonary function [9 and 18 months]

  5. MUNE [9 and 18 months]

  6. Quality of Life [9 and 18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 University of California Los Angeles - Tier 2 Site Pacific Palisades California United States 90272
2 University of California - San Francisco - Tier 2 Site San Francisco California United States 94117
3 University of Colorado Health Sciences Center - Tier 2 Site Denver Colorado United States 80262
4 University of Miami - Tier 2 Site Miami Florida United States 33136
5 Emory University - Tier 2 site Atlanta Georgia United States 30322
6 Northwestern University, Dept. of Neurology - Tier 2 Site Chicago Illinois United States 60611
7 University of Kansas Medical Center - Tier 2 site Kansas City Kansas United States 66160
8 John Hopkins University - Tier 2 Site Baltimore Maryland United States 21287
9 Massachusetts General Hospital - Tier 1 Site Boston Massachusetts United States 02114
10 Baystate Medical Center - Tier 2 Site Springfield Massachusetts United States 01199
11 Saint Louis University, Neuromuscular Div. - Tier 2 Site Saint Louis Missouri United States 63110
12 Washington University - Tier 2 Site St. Louis Missouri United States 63110
13 BryanLGH Medical Center - Tier 2 Site Lincoln Nebraska United States 68506
14 Upstate Clinical Research, LLC - Tier 2 Site Albany New York United States 12205
15 Mount Sinai School of Medicine - Tier 2 Site New York New York United States 10029
16 Columbia University Medical Center - Tier 2 site New York New York United States 10032
17 SUNY Downstate Medical Center - Tier 1 Site Syracuse New York United States 13210
18 Duke University Medical Center - Tier 1 Site Durham North Carolina United States 27705
19 Wake Forest University School of Medicine -Tier 2 Site Winston Salem North Carolina United States 27157
20 Cleveland Clinic Foundation -Tier 2 site Cleveland Ohio United States 44195
21 Providence ALS Center - Tier 2 Site Portland Oregon United States 97213
22 Pennsylvania State University School of Medicine - Tier 2 Site Hershey Pennsylvania United States 17033
23 Drexel University College of Medicine - Tier 1 Site Philadelphia Pennsylvania United States 19107
24 University of Pittsburgh Medical Center - Tier 2 Site Pittsburgh Pennsylvania United States 15213
25 Vanderbilt University Medical Center - Tier 2 Nashville Tennessee United States 37232-2551
26 Texas Neurology, PA - Tier 2 Site Dallas Texas United States 75214
27 University of Texas Health Science Center - Tier 2 Site San Antonio Texas United States 78229-3900
28 University of Vermont, College of Medicine - Tier 2 Burlington Vermont United States 05405
29 University of Virginia - Tier 2 Sites Charlottesville Virginia United States 22908
30 Virginia Mason Clinic - Tier 2 Site Seattle Washington United States 98101
31 Medical College of Wisconsin - Tier 2 Site Milwaukee Wisconsin United States 53226
32 University of British Columbia, Gordon and Leslie Diamond Health Care Centre - Tier 2 Site Vancouver British Columbia Canada V5Z 2G9
33 London Health Science Center - Tier 2 Site London Ontario Canada N6A 5A5
34 University of Toronto, Sunnybrook Health Sciences Centre - Tier 2 Site Toronto Ontario Canada M4N 3M5
35 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
CytRx
ClinicalTrials.gov Identifier:
NCT00561366
Other Study ID Numbers:
  • AALS-003
First Posted:
Nov 20, 2007
Last Update Posted:
Feb 9, 2012
Last Verified:
Feb 1, 2012
Keywords provided by CytRx
ALS
Lou Gehrig's disease
Additional relevant MeSH terms:
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis

Study Results

No Results Posted as of Feb 9, 2012