Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)

Knopp Biosciences

Status and phase: Completed; Phase 2

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Dexpramipexole 300 mg/day; Drug: Dexpramipexole 50 mg/day; Drug: Placebo; Drug: Dexpramipexole 150 mg/day

Study type: Interventional

Funder types: Industry

Identifiers

NCT00647296

KNS-760704-CL201

Details and patient eligibility

About

This was a 2-part study of dexpramipexole in patients with ALS.

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

Part 2 was 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 dexpramipexole for up to 72 weeks.

Full description

This study was a two-part, multicenter, double-blind study in subjects with ALS to evaluate the safety and tolerability of dexpramipexole treatment, as well as the preliminary effects on measures of clinical function and mortality of dexpramipexole treatment.

In part 1, 102 subjects with ALS were randomized at 20 US sites to receive placebo, dexpramipexole at 50 mg/day; dexpramipexole at 150 mg/day; or dexpramipexole at 300 mg/day for 12 weeks. Participants who completed Part 1 were eligible to enroll into Part 2.

Part 2 was a randomized, double-blind, 2-arm, parallel-group, extension study evaluating the longer-term safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole. In part 2, following a 4-week, placebo washout, continuing subjects received dexpramipexole at 50 mg/day or 300 mg/day as double-blind treatment for up to 72 additional weeks (Part 2 duration was up to a total of 76 weeks, including the 4 week placebo portion).

Enrollment: 194 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria
• Patients with ALS symptom onset < 24 months from randomization
• Patients with upright vital capacity (VC) > 65% of predicted for age, height, and gender

Exclusion criteria

• Patients in whom causes of neuromuscular weakness other than ALS have not been excluded
• Patients without clinical evidence of upper motor neuron dysfunction
• Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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194 participants in 3 patient groups, including a placebo group

Part 1: Placebo or Dexpramipexole

Placebo Comparator group

Description:

During Part 1, subjects received twice daily doses of dexpramipexole (50 mg/day, 150 mg/day, or 300 mg/day) or matching placebo for approximately 12 weeks.

Treatment:

Drug: Dexpramipexole 150 mg/day

Drug: Placebo

Drug: Dexpramipexole 50 mg/day

Drug: Dexpramipexole 300 mg/day

Part 2: Placebo washout

Experimental group

Description:

At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.

Treatment:

Drug: Placebo

Part 2: Dexpramipexole

Experimental group

Description:

Following the Part 2 placebo washout, subjects received dexpramipexole (50 mg/day or 300 mg/day), subjects received twice daily doses of placebo for up to 18 months.

Treatment:

Drug: Dexpramipexole 50 mg/day

Drug: Dexpramipexole 300 mg/day