May, 2008

Protocol Title:   A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS‑760704 in Patients with Amyotrophic Lateral Sclerosis (ALS)

Working Titles:  CL201 Study in ALS

PURPOSE AND RATIONALE:

This is a 2-part study of KNS-760704 in patients with ALS.

Part 1 is a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of KNS‑760704 vs. placebo for 12 weeks.

Part 2 is a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of KNS‑760704 for up to 28 weeks.

Both KNS-760704 and pramipexole have been shown to possess neuroprotective properties (properties which protect nerve cells from dying). Several lines of evidence indicate that these compounds target the mitochondrion, the energy-producing cell organelle that is compromised in many neurodegenerative disorders and is believed to play a role in the development of ALS.

STUDY DETAILS:

This is a double-blind, randomized, placebo-controlled study evaluating the safety and efficacy of KNS-760704 compared to placebo. The study will be conducted in 2 parts.

In Part 1, approximately 80 eligible patients will be randomized to 1 of 4 treatment groups for 12 weeks of treatment: placebo; low-dose; mid-dose; or high-dose KNS‑760704. Participants meeting eligibility requirements will be enrolled at approximately 20 centers in the U.S. In addition to the visit to determine eligibility and the first visit to take study drug, participants will be required to make 5 additional research clinic visits in Part 1. 

Participants who complete all 12 weeks of Part 1 will be eligible for randomization to Part 2. The duration of Part 2 of the study is 28 weeks. Participants will receive 1 of 2 active treatment groups for 24 weeks (low-dose or high-dose KNS‑760704) and placebo for the remaining 4-week period in Part 2. Participants will not be told when the 4 weeks of placebo treatment will be given. During Part 2, participants will be required to make 6 research clinic visits, including the baseline visit.

During each visit throughout both parts of the study, participants will be subjected to a series of tests designed to study the safety of the study drug, as well and undergo tests to evaluate the effects of KNS‑760704 on measures of clinical function (e.g., vital capacity, quality of life and ALSFRS-R).

STUDY STATUS / DATES: 

The study is currently open for enrollment and is expected to be enrolling participants in the US until July 2008 (or until 80 participants have been enrolled, whichever is first).

NUMBER OF PARTICIPANTS:

80 participants will be enrolled at 20 US centers.

BASIC ELIGIBILITY REQUIREMENTS:

Inclusion:

• Patients with diagnosis of familial or sporadic ALS

Exclusion:

• Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole)
• Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study

FUNDING:

Knopp Neurosciences Inc.

IRB APPROVAL:

IRB approval has been granted at several sites and recruitment for the study is open.