Phase 1 Dose Escalation and PK Study of Cu(II)ATSM in ALS/MND

NCT02870634 | Completed Phase 1 DMC

• 1 other identifier: CMD-2016-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Multicenter, open-label , single and multiple dose-escalation and pharmacokinetic study

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Outcome Measures

Primary Outcomes (1)

• recommended phase 2 dose as determined by the number of participants at each dose level with dose limiting toxicities

  24 months

Secondary Outcomes (8)

• Treatment-related change in disease severity by ALS Functional Rating Scale - Revised (ALSFRS-R)

  24 months

• Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioral Assessment (ECAS) score

  24 months

• Treatment-related change in respiratory function by seated forced vital capacity (FCV)

  24 months

• Treatment-related change in quality of life by ALSSQOL-R score

  24 months

• Treatment-related change in disease severity by transcranial magnetic stimulation (TMS) response

  24 months

Study Arms (1)

Cu(II)ATSM

EXPERIMENTAL

Cu(II)ATSM capsules, administered orally once daily

Drug: Cu(II)ATSM

Interventions

Cu(II)ATSM DRUG

copper-containing synthetic small molecule

Also known as: diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)

Cu(II)ATSM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to initiation of any study-specific procedures;
• Familial or sporadic ALS/MND defined as clinically possible, probable, or definite by Awaji-shima Consensus Recommendations;
• First ALS/MND symptoms occurred no more than 2 years prior to screening visit;
• Seated FVC ≥ 70% and SNP ≥ 50% of predicted value;
• Not taking riluzole or on a stable dose of riluzole for at least 4 weeks prior to screening visit (participants are not allowed to start taking riluzole during the study);
• Age between 18 and 75 years at time of informed consent;
• Patient has a competent caregiver who can and will be responsible for administration of study drug;
• Adequate bone marrow reserve, renal and liver function:
• absolute neutrophil count ≥ 1500/µL
• lymphocyte count \< 48%
• platelet count ≥ 150,000/µL
• hemoglobin ≥ 11 g/dL
• creatinine clearance ≥ 60 mL/min (Cockroft \& Gault formula)
• ALT and/or AST ≤ 2 x ULN
• total bilirubin ≤ 1.5 x ULN

You may not qualify if:

• Inability to swallow oral medications or presence of GI disorder deemed to jeopardize intestinal absorption of Cu(II)ATSM
• Dependence of mechanical ventilation (non-invasive or invasive) for any part of day or night
• Exposure to any other investigational agent within 3 months or two investigational agents within 6 months prior to screening visit
• Active GI disease (except gastrointestingal reflux disease) within 30 days of screening visit
• Known immune compromising illness or treatment
• Presence of any of the following clinical conditions
• drug abuse or alcoholism
• unstable cardiac, pulmonary, renal, hepatic, endocrine or hematologic disorder
• active infectious disease
• AIDS or AIDS-related complex
• current malignancy
• unstable psychiatric illness, defined as psychosis or untreated major depression within 90 days of screening visit
• neuromuscular disease other than ALS/MND
• Dementia that may affect either outcome measures or patient understanding and/or compliance with study requirements and procedures
• Use of anticoagulants at therapeutic doses within 7 days prior to screening visit

Sponsors & Collaborators

• Collaborative Medicinal Development Pty Limited: lead

Study Sites (2)

Macquarie University

Sydenham, New South Wales, 2109, Australia

Location

Calvary Health Care Bethlehem

Caulfield, Victoria, 3162, Australia

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); Copper

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Dominic Rowe, MD

  Macquarie University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: August 17, 2016
• Study Start: November 16, 2016
• Primary Completion: October 30, 2019
• Study Completion: January 30, 2020
• Last Updated: March 17, 2020

Record last verified: 2020-03

Locations

AU (2)