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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Collaborative Medicinal Development Pty Limited
Sponsor:
Information provided by (Responsible Party):
Collaborative Medicinal Development Pty Limited
ClinicalTrials.gov Identifier:
NCT02870634
First received: August 10, 2016
Last updated: March 6, 2017
Last verified: March 2017
  Purpose
Multicenter, open-label , single and multiple dose-escalation and pharmacokinetic study

Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Drug: Cu(II)ATSM
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Single and Multiple Dose Escalation and Pharmacokinetic Study of Cu(II)ATSM Administered Orally to Patients With Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Resource links provided by NLM:


Further study details as provided by Collaborative Medicinal Development Pty Limited:

Primary Outcome Measures:
  • recommended phase 2 dose as determined by the number of participants at each dose level with dose limiting toxicities [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Treatment-related change in disease severity by ALS Functional Rating Scale - Revised (ALSFRS-R) [ Time Frame: 24 months ]
  • Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioral Assessment (ECAS) score [ Time Frame: 24 months ]
  • Treatment-related change in respiratory function by seated forced vital capacity (FCV) [ Time Frame: 24 months ]
  • Treatment-related change in quality of life by ALSSQOL-R score [ Time Frame: 24 months ]
  • Treatment-related change in disease severity by transcranial magnetic stimulation (TMS) response [ Time Frame: 24 months ]
  • Peak Cu(II)ATSM plasma concentration following administration of a single dose based on blood draws taken at 1, 2, 4, 8 and 24 hours after dosing [ Time Frame: 12 months ]
  • Area under the Cu(II)ATSM plasma concentration versus time curve (AUC) following administration of a single dose based on blood draws taken at 1, 2, 4, 8 and 24 hours after dosing [ Time Frame: 12 months ]
  • Treatment-related change in respiratory function by sniff nasal pressure (SNP) test [ Time Frame: 24 months ]

Estimated Enrollment: 50
Study Start Date: October 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cu(II)ATSM
Cu(II)ATSM capsules, administered orally once daily
Drug: Cu(II)ATSM
copper-containing synthetic small molecule
Other Name: diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)

Detailed Description:

Multicenter, open-label, phase 1 study of Cu(II)ATSM administered orally to patients wit amyotrophic lateral sclerosis/motor neuron disease. The study will be conducted in three phases. In the first two phases, dose cohorts of six patients each will participate in a single dose pharmacokinetic study followed by a 28-day repeated daily dose study to establish the recommended phase 2 dose (RP2D). The first dose cohort will be treated at 3 mg/day; planned dose escalations are 6, 12, 24, and 48 mg/day, subject to observed safety assessments. In the third phase of the study, participants will be treated at the RP2D to confirm tolerability and assess preliminary evidence of efficacy.

In both the dose escalation and expansion cohorts, once the first 28 days of treatment and assessments are completed, at the discretion of the investigator a patient may continue to receive Cu(II)ATSM treatment for a maximum of six 28-day treatment cycles.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
    • serum albumin ≥ 2.8 g/dL
  • Women and men with partners of childbearing potential must take effective contraception while on study and women of childbearing potential must have a negative pregnancy test and be non-lactating at screening

Exclusion Criteria:

  • 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
  • Current use of strong inducers or inhibitors of CYPs 2C19 and 2D6
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02870634

Contacts
Contact: Kay Noel, PhD 415 444 9602 kay.noel@ColMedDev.com
Contact: Craig Rosenfeld, MD 415 444 9602 CraigR@ColMedDev.com

Locations
Australia, New South Wales
Macquarie University Recruiting
Sydenham, New South Wales, Australia, 2109
Contact: Dominic Rowe, AM, BSc(Med),PhD         
Australia, Victoria
Calvary Health Care Bethlehem Recruiting
Caulfield, Victoria, Australia, 3162
Contact: Susan Mathers, MD    (03)9593355    susan.mathers@calvarycare.org.au   
Sponsors and Collaborators
Collaborative Medicinal Development Pty Limited
Investigators
Principal Investigator: Dominic Rowe, MD Macquarie University
  More Information

Responsible Party: Collaborative Medicinal Development Pty Limited
ClinicalTrials.gov Identifier: NCT02870634     History of Changes
Other Study ID Numbers: CMD-2016-001
Study First Received: August 10, 2016
Last Updated: March 6, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Copper
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 28, 2017