Toward more efficient clinical trials for amyotrophic lateral sclerosis.
More than 30 phase II or III clinical trials have been carried out in amyotrophic lateral sclerosis (ALS). Only riluzole, however, has been shown to extend survival and/or time to tracheostomy. Many early ALS trials lacked solid pharmacodynamic and pharmacokinetic data for the treatment being tested, challenging the interpretation of the efficacy and pathway relevance. Understanding of the genetics and pathophysiology of ALS has improved considerably in the past decade, but biomarkers of disease activity remain lacking. A more efficient approach to early phase clinical trials is needed to accelerate the identification of useful agents for ALS. Here we summarize our current thinking about phase II design options and the potential benefits of a clinical trial network for phase II trials in ALS.
Cudkowicz
Merit E
ME
Massachusetts General Hospital, Boston, Massachusetts, USA. mcudkowicz@partners.org
Katz
Jon
J
Moore
Dan H
DH
O'Neill
Gilmore
G
Glass
Jonathan D
JD
Mitsumoto
Hiroshi
H
Appel
Stanley
S
Ravina
Bernard
B
Kieburtz
Karl
K
Shoulson
Ira
I
Kaufmann
Petra
P
Khan
Jaffar
J
Simpson
Ericka
E
Shefner
Jeremy
J
Levin
Bruce
B
Cwik
Valerie
V
Schoenfeld
David
D
Aggarwal
Swati
S
McDermott
Michael P
MP
Miller
Robert G
RG
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012107:Research Design; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D018696:Neuroprotective Agents; D019782:Riluzole