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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04894240




Registration number
NCT04894240
Ethics application status
Date submitted
5/05/2021
Date registered
20/05/2021

Titles & IDs
Public title
A Study of Monepantel in Individuals With Motor Neurone Disease
Scientific title
A Phase I Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy Study of Oral Monepantel in Individuals With Motor Neurone Disease
Secondary ID [1] 0 0
MON-2021-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Monepantel

Experimental: Monepantel treatment arm - Monepantel tablets will be administered to participants in this arm daily for 28 days. Dose escalation will occur at the end of each 28 day period according to a modified Fibonacci sequence based upon recommendations from the safety management committee


Treatment: Drugs: Monepantel
Monepantel is provided to individuals living with ALS/MND as a white oval tablet to be administered once a day following meals
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of Phase 2 Dose
Timepoint [1] 0 0
At least 4 weeks
Primary outcome [2] 0 0
Blood Plasma Pharmacokinetics of Monepantel
Timepoint [2] 0 0
0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours and 2, 8, 15, 22 and 29 days after dosing
Primary outcome [3] 0 0
Blood Plasma Pharmacokinetics of Monepantel Sulfone
Timepoint [3] 0 0
0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours and 2, 8, 15, 22 and 29 days after dosing
Secondary outcome [1] 0 0
Treatment related changes in peripheral blood mononuclear cell phosphorylated ribosomal protein S6 kinase B1 (RPS6KB1) levels (pharmacodynamics)
Timepoint [1] 0 0
From admission to discharge, up to 6 months
Secondary outcome [2] 0 0
Treatment related changes in peripheral blood mononuclear cell phosphorylated eukaryotic initiation factor 4 E binding protein 1 (EIF4EBP1) levels (pharmacodynamics)
Timepoint [2] 0 0
From admission to discharge, up to 6 months
Secondary outcome [3] 0 0
Treatment-related changes from Baseline on the ALS Functional Rating Scale (ALSFRS) at Week 4
Timepoint [3] 0 0
From admission to discharge, up to 6 months
Secondary outcome [4] 0 0
Treatment-related changes from Baseline in Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) at Week 4
Timepoint [4] 0 0
From admission to discharge, up to 6 months
Secondary outcome [5] 0 0
Treatment-related changes from Baseline in slow vital capacity (SVC)
Timepoint [5] 0 0
From admission to discharge, up to 6 months
Secondary outcome [6] 0 0
Treatment-related changes in urinary p75 levels
Timepoint [6] 0 0
From admission to discharge, up to 6 months
Secondary outcome [7] 0 0
Treatment-related changes in 3 Tesla magnetic resonance imaging (MRI)
Timepoint [7] 0 0
From admission to discharge, up to 6 months
Secondary outcome [8] 0 0
Treatment-related changes in serum neurofilament light (NfL) chain levels
Timepoint [8] 0 0
From admission to discharge, up to 6 months
Secondary outcome [9] 0 0
Treatment-related changes in central spinal fluid (CSF) NfL chain levels
Timepoint [9] 0 0
From admission to discharge, up to 6 months

Eligibility
Key inclusion criteria
* Signed informed consent obtained prior to initiation of any study-specific procedures and treatment
* Familial or sporadic ALS/MND diagnosed as clinically possible, probable, or definite according to Awaji-shima Consensus Recommendations
* Seated slow vital capacity (SVC) = 3L in males and = 2.5L in females at screening
* Not taking riluzole or on a stable dose of riluzole for at least 4 weeks prior to the screening visit. While on study, subjects are not allowed to start taking riluzole during the study
* Patient has a competent caregiver who can support the patient's involvement in the study, including assisting the administration of study drug
* Adequate bone marrow reserve, renal and liver function:

1. absolute neutrophil count (ANC) =1500/µL;
2. platelet count = 100,000/µL;
3. hemoglobin = 9 g/dL;
4. creatinine clearance = 60 mL/min (Cockroft & Gault formula);
5. alanine aminotransferase ALT, SGPT) and/or aspartate aminotransferase (AST, SGOT)
6. = 2 x upper limit of normal (ULN);
7. total bilirubin = 1.5 x ULN;
8. serum albumin = 2.8 g/dL
* Women and men with partners of childbearing potential must use effective contraception while on study treatment and women of childbearing potential must have a negative pregnancy test at screening
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability to swallow oral medications or presence of a gastrointestinal disorder (e.g., malabsorption) deemed to jeopardize intestinal absorption of study drug
* Dependence on mechanical ventilation (invasive or non-invasive, including Continuous Positive Airway Pressure (CPAP) or Bi-level Positive Airway Pressure (BiPAP) for any part of day or night prior to the screening visit. Dependence on mechanical ventilation is defined as being unable to lie flat (supine) without it, unable to sleep without it, or daytime use
* Exposure to any other investigational agent within 3 months prior to the screening visit
* Active gastrointestinal disease within 30 days of the screening visit. Gastro-esophageal reflux disease (GERD) is not considered active gastrointestinal disease and is not exclusionary
* Known immune compromising illness or treatment
* Presence of any of the following clinical conditions:

1. drug abuse or alcoholism;
2. unstable cardiac, pulmonary, renal, hepatic, endocrine, or hematologic disease;
3. active infectious disease;
4. AIDS or AIDS-related complex;
5. diagnosis of malignancy within 2 years of screening (adequately treated basal cell or squamous cell carcinoma of skin or non-invasive bladder cancer or carcinoma in situ of the bladder, breast or cervix are allowed;
6. unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit;
7. neuromuscular disease other than ALS/MND
* Dementia that may affect either outcome measures or patient understanding and/or compliance with study requirements and procedures
* Women and men of childbearing potential not using effective contraception while on study treatment
* Women who are breast-feeding
* Patients at risk of or known to carry a SOD1 mutation or VCP mutation

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/11/2023
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie University - Sydney
Recruitment hospital [2] 0 0
Calvary Health Care Bethlehem - Melbourne
Recruitment postcode(s) [1] 0 0
2109 - Sydney
Recruitment postcode(s) [2] 0 0
3195 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
PharmAust Ltd
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
FightMND
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Calvary Health Care Bethlehem
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Macquarie University, Australia
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Susan Mathers, MB ChB, MRCP(UK), FRACP
Address 0 0
Calvary Health Care Bethlehem
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04894240