**5.3.2 AEOL-10150**

10 Amyotrophic Lateral Sclerosis

Since there has been an early release of information about the efficacy in clinical ALS trials, which had to be revoked after thorough analysis, any information with regard to the efficacy of an investigational drug should only be released when peer-reviewed publication is at least imminent (with the exception of scientific meetings). The investigator is

The design of ALS trials should comprehend three phases (Brooks, 1997). In phase I, toxicity and pharmacokinetics is tested. In phase II (pilot, exploratory, or screening trials) information is gathered about dose finding, preliminary efficacy, and further safety observations. In phase III, definitive efficacy and safety is evaluated. Phase I trials should incorporate a placebo control group and the follow-up should be at least six months. Phase II trials may use placebo controls, historic controls, or a crossover design. If the prospective therapeutic value aims at improvement of signs and symptoms, such as increased muscle strength or ameliorated function, the follow-up should be at least six months, whereas trials aiming at stabilization or slowing of deterioration should observe the patients' condition for at least 12 months (Bedlack, 2010). All phase III trials should be placebo-controlled. The endpoints should include at least the survival time, assessment of strength measured by maximum voluntary isometric contraction, pulmonary function, and functional performance by the ALS rating scale. Of course, an independent data and safety monitoring

Of note, since survival times are rather short, many patients feel desperate and take unapproved medication out of the reach of a clinical trial. By establishing these consensus

In the following "inventory" of clinical trials in ALS, I will give an overview over drug candidates used in ALS trials. I have included all interventional clinical trials registered at Clinicaltrials.gov (http://clinicaltrials.gov/). Information on these trials can be obtained by accessing the website http://ClinicalTrials.gov/show/NCTxxx, where xxx stands for the

Since there have been various clinical trials in the era before Clinicaltrials.gov required registration, and before a consensus conference established criteria for ALS trials (Miller et al., 1999), I have included some information on earlier trials. On the other hand, I excluded case reports, trials with nutritional supplements, and non-pharmacological therapeutic procedures such as plasma exchange, whole-body irridation, hyperbaric oxygenation, balneotherapy, cervico-dorsal electroshock therapy, adrenal cortex injection or stem cell injection, even when the stem cells are used as vehicles and vectors for the expression of

Of note, this inventory is neither comprehensive, nor does it contain all available references due to space restriction. It is mainly based on a selective literature search in the PubMed database, and summarizes recent reviews in the field (Carlesi et al., 2011; Miller et al., 2005;

The anti-oxidant N-acetylcysteine did not show efficacy in a phase II clinical trial (Louwerse

Siciliano et al., 2010; Zinman & Cudkowicz, 2011; Zoccolella et al., 2009).

guidelines, this potentially dangerous drug use may be reduced (Ross, 2009).

**5.3 Overview over drug candidates in clinical ALS trials** 

responsible for any conflict of interest.

board should be established.

registration number shown below.

biologicals.

et al., 1995).

**5.3.1 N-acetylcysteine** 

AEOL-10150 is a metalloporphyrin scavenging reactive oxygen species (ROS) (Orrell, 2006). It has been tested for safety and tolerability in three phase I trials, but further development has been halted.
