CuATSM Compared With Placebo for Treatment of ALS/MND

Study Overview
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Brief Summary
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Multicenter, randomized, double-blind, placebo controlled study to assess the tolerabilty and efficacy of CuATSM in patients with ALS/MND. Patients will be randomized 1:1 to CuATSM or placebo for 6 x 28-day cycles (24 weeks) of treatment.

Detailed Description
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Patients will be randomized 1:1 to CuATSM or placebo for 6 x 28-day cycles (24 weeks) of treatment. Study drug is administered orally, once a day in fasted state (before breakfast). Assessments for safety (physical examination, vital signs, hematology, serum chemistry adverse events) will be conducted at baseline and following each cycle of treatment. Assessments for efficacy (Revised ALS Functional Rating Scale [ASLFRS-R] score, and Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen [ECAS] score, and seated slow vital capacity [SVC]) will be conducted at baseline and following 2, 4 and 6 cycles of treatment. Analysis of covariance (ANCOVA) will be used to compare efficacy endpoints between CuATSM and placebo groups.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Cu(II)ATSM in Patients With Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Cu(II)ATSM
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent familial or sporadic ALS/MNS by Awaji-shima Consensus Recommendations not taking riluzole or on stable dose of riluzole for 4 weeks prior to screening visit no prior exposure to agents other than riluzole for treatment of ALS adequate bone marrow reserve, renal and liver function women of childbearing potential must have a negative pregnancy test and be non-lactating women and men with partners of childbearing potential must take effective contraception while on treatment Exclusion Criteria: presence of a gastrointestinal disorder (eg, malabsorption) that might jeopardize intestinal absorption of study drug inability to perform seated SVC known immune compromising illness or treatment drug abuse or alcoholism clinically significant or active cardiovascular disease acute or chronic infection diagnosis of malignancy within 2 years prior to screening dementia that may affect patient understanding and/or compliance with study requirements and procedures current use of strong inducers or inhibitors of CYPs 2C19 and 2D6 current us of medications (other than riluzole) that are metabolized predominantly by CYP 1A2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: ANCOVA will be used to compare efficacy endpoints between CuATSM and placebo groups
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cu(II)ATSM<br>Cu(II)ATSM Powder for Oral Suspension, 36 mg, to be reconstituted with Diluent (15 mL of sugar-free flavored pharmaceutical syrup) to provide an oral suspension for immediate consumption. Specified dose is 72 mg (2 bottles) taken fasting, before breakfast each day. | Drug: Cu(II)ATSM<br>* oral suspension<br>|
| Placebo Comparator: Placebo Powder for Oral Suspension<br>Placebo Powder for Oral Suspension, to be reconstituted with Diluent (15 mL of sugar-free flavored pharmaceutical syrup) to provide an oral suspension for immediate consumption. Specified dose is 72 mg (2 bottles) taken fasting, before breakfast each day. | Drug: Placebos<br>* oral suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Revised ALS Functional Rating Scale (ALSFRS-R) total score (range: 48 [best] to 0 [worst]) | assessment of disease severity | 24 weeks | 
| Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) total score (range: 136 [best] to 0 [worst]) | assessment of cognitive function | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seated slow vital capacity (SVC) | assessment of respiratory function | 24 weeks | 
| rate of adverse events | tolerability assessment | 24 weeks |