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

March 15, 2020 updated by: Collaborative Medicinal Development Pty Limited

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydenham, New South Wales, Australia, 2109
        • Macquarie University
    • Victoria
      • Caulfield, Victoria, Australia, 3162
        • Calvary Health Care Bethlehem

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cu(II)ATSM
Cu(II)ATSM capsules, administered orally once daily
Drug: Cu(II)ATSM
copper-containing synthetic small molecule
Other Names:
  • diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
recommended phase 2 dose as determined by the number of participants at each dose level with dose limiting toxicities
Time Frame: 24 months
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Treatment-related change in disease severity by ALS Functional Rating Scale - Revised (ALSFRS-R)
Time Frame: 24 months
24 months
Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioral Assessment (ECAS) score
Time Frame: 24 months
24 months
Treatment-related change in respiratory function by seated forced vital capacity (FCV)
Time Frame: 24 months
24 months
Treatment-related change in quality of life by ALSSQOL-R score
Time Frame: 24 months
24 months
Treatment-related change in disease severity by transcranial magnetic stimulation (TMS) response
Time Frame: 24 months
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
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
12 months
Treatment-related change in respiratory function by sniff nasal pressure (SNP) test
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Collaborative Medicinal Development Pty Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 16, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 10, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 17, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 15, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CMD-2016-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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