- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02870634
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
Study Overview
Status
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
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New South Wales
-
Sydenham, New South Wales, Australia, 2109
- Macquarie University
-
-
Victoria
-
Caulfield, Victoria, Australia, 3162
- Calvary Health Care Bethlehem
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
|
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
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Sclerosis
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- Physiological Effects of Drugs
- Trace Elements
- Micronutrients
- Copper
Other Study ID Numbers
- CMD-2016-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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
-
University of EdinburghUniversity College, London; NHS Lothian; University of WarwickRecruitingMotor Neuron Disease, Amyotrophic Lateral SclerosisUnited Kingdom
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingProgressive Motor Neuron Disease Without Definite Diagnosis
-
Hospital for Special Surgery, New YorkActive, not recruiting
-
Bioinova, s.r.o.Department of Neurology, University Hospital Motol, Prague, Czech RepublicCompletedMotor Neuron Disease, Amyotrophic Lateral Sclerosis
-
National Institute of Neurological Disorders and...Completed
-
Liverpool University Hospitals NHS Foundation TrustNot yet recruitingMotor Neuron Disease, Amyotrophic Lateral Sclerosis
-
Washington University School of MedicineEnrolling by invitationMotor Neuron Disease | Amyotrophic Lateral Sclerosis | Lou Gehrig Disease | Familial Amyotrophic Lateral Sclerosis | Motor Neuron Disease, FamilialUnited States
-
MedRegen LLCNot yet recruitingMotor Neuron Disease | Amyotrophic Lateral Sclerosis | Lou Gehrig Disease | Motor Neuron Atrophy
-
Ambulanzpartner Soziotechnologie APST GmbHCharite University, Berlin, GermanyRecruitingMotor Neuron Disease, Amyotrophic Lateral SclerosisGermany
-
Ottawa Hospital Research InstituteRecruitingTetraplegia | Motor Neuron Disease, Amyotrophic Lateral SclerosisCanada
Clinical Trials on Cu(II)ATSM
-
Collaborative Medicinal Development Pty LimitedUnknown
-
Collaborative Medicinal Development Pty LimitedCompleted
-
Collaborative Medicinal Development Pty LimitedActive, not recruiting
-
Collaborative Medicinal Development Pty LimitedCompletedAmyotrophic Lateral SclerosisAustralia
-
University of California, San FranciscoAgency for Healthcare Research and Quality (AHRQ); San Francisco Health Plan...Completed
-
Institut Cancerologie de l'OuestFondation ARCActive, not recruiting
-
Cutia Therapeutics(Wuxi)Co.,LtdCompleted
-
Agency for Healthcare Research and Quality (AHRQ)The Commonwealth Fund; California HealthCare FoundationCompleted
-
University of California, San FranciscoNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Completed
-
Clarity Pharmaceuticals LtdCompleted