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

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

Completed

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

50

Phase

  • 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

    • 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

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
Intervention / Treatment
EXPERIMENTAL: Cu(II)ATSM
Cu(II)ATSM capsules, administered orally once daily
copper-containing synthetic small molecule
Other Names:
  • diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)

What is the study measuring?

Primary Outcome Measures

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

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.

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)

November 16, 2016

Primary Completion (ACTUAL)

October 30, 2019

Study Completion (ACTUAL)

January 30, 2020

Study Registration Dates

First Submitted

August 10, 2016

First Submitted That Met QC Criteria

August 12, 2016

First Posted (ESTIMATE)

August 17, 2016

Study Record Updates

Last Update Posted (ACTUAL)

March 17, 2020

Last Update Submitted That Met QC Criteria

March 15, 2020

Last Verified

March 1, 2020

More Information

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.

Clinical Trials on Motor Neuron Disease

Clinical Trials on Cu(II)ATSM

3
Subscribe