DISEASE CLASSIFICATION(S):
Amyotrophic Lateral Sclerosis(ALS)
NAME OF CLINICAL TRIAL/STUDY:
Combination Drug Selection Trial
TRIAL RESULTS:
December 2007
At the 18th International Symposium on ALS/MND in Toronto, lead investigator Paul Gordon, M.D., announced the selection of the AL-08 (a creatine derivative developed by Avicena Group of Palo Alto, Calif.) plus celecoxib combination over the AL-08 plus minocycline combination. The AL-08 plus celecoxib group showed less decline in ALS Functional Rating scores compared to the AL-08 minocycline group and a historical (from the past), untreated group. The AL-08 plus celecoxib combination is being considered for further investigation.
See Avicena Announces Positive Phase II Data for a Combination Trial Involving AL-08 for the Treatment of Amyotrophic Lateral Sclerosis (ALS).
TRIAL UPDATES:
October 2006
According to an Oct. 18, 2006, press release from the Avicena Group, which developed the creatine derivative ALS-08, enrollment for the first stage of this phase 2 trial is complete. Eighty-six patients have been enrolled.
Patients were randomly assigned to one of two combination treatment arms: ALS-08 and minocycline or ALS-08 and celecoxib.
The investigators will assess the mean difference in ALSFRS-R (revised ALS Functional Rating Scale) between the two treatment arms. If the mean (average) difference between the two treatment groups achieves a pre-defined value, the trial will be judged to be complete.
If the pre-defined difference value is not achieved, this phase 2 trial will continue into a second enrollment stage. For the second stage, up to an additional 60 patients would be enrolled and randomly assigned to one of the two treatment arms.
Following trial completion, the superior combination therapy will be selected for further study in a phase 3 clinical trial.
PURPOSE AND RATIONALE:
Excess free radicals (toxic byproducts of cellular metabolism), energy mishandling, excitotoxicity (toxicity from activating signals, such as those from glutamate), activation of cell death pathways and inflammation likely all contribute to neurodegeneration in ALS.
Past trials may have been negative in part because they tested single agents, usually influencing only one mechanism of cell death. Combinations of agents that affect different and multiple mechanisms of neurodegeneration may be necessary to reach meaningful outcomes in trials of ALS.
This study will test minocycline with a creatine derivative known as ALS-08 (developed by Avicena Group, Palo Alto, Calif.), and celecoxib (Celebrex) with the ALS-08 creatine derivative. Combinations of minocycline and creatine, and of celecoxib and creatine, have had additive effects in a mouse model of ALS, reducing neurodegeneration and prolonging survival more than individual agents alone.
STUDY DETAILS:
This is a six-month, multicenter, phase 2 trial, with a double-blind design, meaning neither investigators nor participants will know who is taking which drugs and that participants will be randomly assigned to one combination or the other.
The investigators will compare the two combinations of drugs to determine which, if either, is superior at slowing the progression of ALS, using the ALS Functional Rating Scale (revised version) as an end point. If one combination appears successful, the trial will lead directly to a phase 3 study of the selected combination.
If this particular trial design is found useful, this trial will also lead to larger phase 2 selection trials assessing greater numbers of agents simultaneously, thereby improving the efficiency of drug screening in ALS.
The study’s primary end point is a change in the ALS Functional Rating Scale, but investigators will also assess a number of secondary outcomes, including safety and tolerability, as well as additional measurements of effectiveness.
The lead investigator for this study is Paul H. Gordon, M.D., co-director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York.
OPENING DATES:
Jul 1 2006
CLOSING DATES:
Oct 1 2006
TARGET NUMBER OF PARTICIPANTS:
up to 120
RECRUITMENT STATUS:
Closed
ELIGIBILITY REQUIREMENTS:
Participants must:
- be between 21 and 85 years of age
- have experienced onset of ALS fewer than five years ago
- have a forced vital capacity (respiratory measurement) of 60 percent or greater
