OBJECTIVE: To examine the safety and tolerability as well as the preliminary 
efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent 
protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral 
sclerosis (ALS).
METHODS: This was a double-blind, placebo-controlled trial in which patients 
with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive 
arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures 
were performed using a mix of in-person and remote assessments. Primary outcome 
was safety and tolerability. Secondary outcome was efficacy, with survival as 
the principal measure. Additional efficacy measures were the rates of decline of 
the Revised ALS Functional Rating Scale (ALSFRS-R) and percent predicted forced 
expiratory volume in 6 seconds (FEV6), and the Combined Assessment of Function 
and Survival (CAFS).
RESULTS: Thirty-eight participants were randomized. Thirty-six (19 placebo, 17 
arimoclomol) were included in the prespecified intent-to-treat analysis. Apart 
from respiratory function, groups were generally well-balanced at baseline. 
Adverse events occurred infrequently, and were usually mild and deemed unlikely 
or not related to study drug. Adjusting for riluzole and baseline ALSFRS-R, 
survival favored arimoclomol with a hazard ratio of 0.77 (95% confidence 
interval [CI] 0.32-1.80). ALSFRS-R and FEV6 declined more slowly in the 
arimoclomol group, with treatment differences of 0.5 point/month (95% CI -0.63 
to 1.63) and 1.24 percent predicted/month (95% CI -2.77 to 5.25), respectively, 
and the CAFS similarly favored arimoclomol.
CONCLUSIONS: This study provides Class II evidence that arimoclomol is safe and 
well-tolerated at a dosage of 200 mg tid for up to 12 months. Although not 
powered for therapeutic effect, the consistency of results across the range of 
prespecified efficacy outcome measures suggests a possible therapeutic benefit 
of arimoclomol.
CLINICALTRIALSGOV IDENTIFIER: NCT00706147.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 
arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 
months. The study lacked the precision to conclude, or to exclude, an important 
therapeutic benefit of arimoclomol.