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This study has been withdrawn prior to enrollment.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

  Show 35 Study Locations
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:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on October 30, 2014