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

2014-08-27 03:34:59 | BioPortfolio

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.

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

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

Conditions

Amyotrophic Lateral Sclerosis

Intervention

Placebo, Arimoclomol

Location

University of California Los Angeles - Tier 2 Site
Pacific Palisades
California
United States
90272

Status

Terminated

Source

CytRx

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:34:59-0400

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Medical and Biotech [MESH] Definitions

A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.

A superoxide dismutase (SOD1) that requires copper and zinc ions for its activity to destroy SUPEROXIDE FREE RADICALS within the CYTOPLASM. Mutations in the SOD1 gene are associated with AMYOTROPHIC LATERAL SCLEROSIS-1.

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A widely-expressed protein of approximately 400 to 500 amino acids. Its N-terminal region (DENN domain) interacts with RAB GTP-BINDING PROTEINS and may regulate AUTOPHAGY, as well as PROTEIN TRANSPORT to ENDOSOMES. Expansion of the GGGGCC hexanucleotide repeat in the first intron of the C9orf72 gene is associated with FRONTOTEMPORAL DEMENTIA with AMYOTROPHIC LATERAL SCLEROSIS (FTDALS1).

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