Motor Neuron DiseasePhase 1NCT06177431
An Open Label Extension Study of Monepantel in Individuals With Motor Neurone Disease
A Phase 1 study testing Monepantel in people with Motor Neuron Disease, run by Neurizon Therapeutics Limited at 2 sites in Australia.
Trial summary
This study is a multicenter, 12-month open label extension study, following Phase 1 Study MON-2021-001, with a single dose of monepantel (MPL) once daily (QD) for the treatment of individuals with MND. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Motor Neuron Disease
- What is being tested?
- Monepantel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesAustralia
- Study dates
- 13 Feb 2024to 30 May 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent obtained prior to initiation of any study specific procedures and treatment.
- Individuals who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Able to swallow study drug tablets.
- Individuals must have completed Study MON-2021-001 and, in the opinion of the investigator, have been compliant with the study procedures and study treatment.
- Diagnosis of ALS/MND defined as clinically possible, probable, or definite according to Awaji-shima Consensus Recommendations.
- Not taking riluzole or on a stable dose of riluzole for at least 4 weeks prior to the screening visit; subjects are not allowed to start taking riluzole during the study.
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- Individual has a competent caregiver/support person who can and will be able to support the individual's participation in the study, including assisting with the administration of study drug.
- Adequate bone marrow reserve, renal and liver function:
- absolute neutrophil count ≥ 1500/µl.
- platelet count ≥ 120,000/µl.
- hemoglobin ≥ 11 g/dL.
- creatinine clearance ≥ 60 mL/min (Cockroft \& Gault formula).
- alanine aminotransferase and/or aspartate aminotransferase ≤ 3 x upper limit of normal.
- total bilirubin ≤ 2.0 x ULN.
- 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 be non-lactating.
Who cannot join
- Inability to swallow oral medications or presence of a gastrointestinal disorder (e.g., malabsorption) deemed to jeopardize intestinal absorption of study drug.
- Participated in another investigational drug research study within 4 weeks (28 days) of the Baseline Visit or five half-lives of the drug, whichever is longer.
- Any other significant illness or condition that in the opinion of the study investigator would interfere with the study conduct.
- Dementia that may affect either outcome measures or subject 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.
- Individuals at risk of or are known to carry a SOD1 mutation or VCP mutation.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Calvary Health Care Bethlehem
Melbourne, Victoria, 3195
Macquarie University
Sydney, New South Wales, 2109
About this study
Official title: An Open Label Extension Study to Investigate the Long Term Safety, Tolerability And Efficacy of Oral Monepantel in Individuals With Motor Neurone Disease Who Previously Completed Study MON-2021-001
This study is a multicenter, 12-month open label extension study, following Phase 1 Study MON-2021-001, with a single dose of monepantel (MPL) once daily (QD) for the treatment of individuals with MND.
Read the detailed description
ALS/MND is a progressive, fatal neurodegenerative disease; characterized by motor neuron loss resulting in muscle weakness and atrophy, disability, and eventually death from failure of the ventilatory muscles. The median age of onset is 55 years and average survival is 3-5 years after onset of the first symptoms. The only FDA-approved disease modifying medications confer only a modest survival benefit. Given the poor prognosis and dearth of effective treatments, clinical studies are of primary importance for people with ALS/MND.
Abnormal protein accumulation within motor neurons of the brain associates with the cause of ALS/MND. Inhibition of the mTOR signaling pathway slows disease progression in certain preclinical models of ALS/MND and is suggested to provide synergy with the ALS/MND standard-of-care drug, riluzole. PharmAust has shown that MPL and its major metabolite MPL sulfone (MPLS) have activity against mTOR signaling pathways in humans; based on published data, the inhibition of mTOR may be relevant to the treatment of ALS/MND.
This Phase I Open Label Extension will further test the hypotheses that MPL administration to individuals living with ALS/MND will safely reduce disease associated protein accumulation in motor neurons and provide therapeutic benefit. The safety and tolerability of oral monepantel administration and markers of efficacy will continue to be tested in the same participants that completed the Phase I Study (MON-2021-001).
A daily dose of 10 mg/kg monepantel (QD) will be studied in the Open Label Extension Study (MON-2023-001) to further evaluate long-term safety and efficacy in participants with MND/ALS that completed the Phase I Study (MON-2021-001). Based on the previous pre-clinical efficacy data and clinical safety data, a dose of 10 mg/kg QD is estimated to produce the most robust mTOR inhibition while still being well tolerated. The 10 mg/kg QD dose was the maximum dose evaluated in the Phase 1 Study.
- Conditions
- Motor Neuron Disease
- Being tested
- Monepantel
- Medical subject headings
- Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MonepantelDrug
Monepantel is provided to individuals living with ALS/MND as a white oval tablet to be administered once a day following meals
| Study group | Role | What they receive |
|---|---|---|
| Monepantel treatment arm | Experimental | Daily dose of 10 mg/kg body weight (QD) Receives: Drug: Monepantel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term safety and tolerability
Assess long-term safety and tolerability of 10 mg/kg body weight (BW) once daily (QD) of monepantel in individuals with Motor Neurone Disease (MND)
Measured: From Baseline to End of Treatment, up to 12 months.
Secondary outcomes (7)
Treatment-related changes in serum neurofilament light (NfL) chain levels
Serum NfL chain levels correlate with disease progression, so stable NfL levels would correlate with stable disease (pg/ml)
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in urinary p75 levels
Urinary p75 level reflect nerve damage and therefore increased levels would act as a proxy to disease progression (ng/mg creatinine)
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes on the ALS Functional Rating Scale (ALSFRS)
The ALS Functional Rating Scale (ALSFRS) is a validated rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis (ALS). Measurements include: (1) speech (2) salivation (3) swallowing (4) handwriting (5) cutting food and handling utensils (with or without gastrostomy) (6) dressing and hygiene (7) turning in bed and adjusting bed clothes (8) walking (9) climbing stairs and (10) breathing. Possible scores range from 0 (normal function) to 4 (severe loss of function). Change = (Week 4 score - Baseline score)
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes on the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS)
The ECAS-cognitive screen is a validated screen comprises 16 items organized into two sub-scales. An ALS-specific sub-scale taps into the cognitive domains of language, verbal fluency, and executive and social functions. A non-ALS-specific sub-scale specifically assesses memory and visuospatial function. The sub-scales of the ECAS-cognitive screen range, respectively, from 0 to 100 and from 0 to 36. Low scores indicate a greater deficit. Change = (Week 4 score - Baseline score)
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in slow vital capacity (in participants with the capacity to undergo testing)
A decline in SVC would indicate a decline in respiratory function and is an important indicator of any clinical progression (L/s)
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in Quality of Life (QOL) Assessment: ALSSQOL-R
ALSSQOL-R is a 50-item disease-specific questionnaire. Each item is rated on a 10-point Likert scale, with 0 being the least desirable situation and 10 being the most desirable. The instrument produces a single-item QoL score and six domain scores (negative emotion, interaction with people and environment, intimacy, religiosity, physical symptoms, and bulbar function). The ALSSQOL-R is used as QoL outcomes measure to examine the effects of experimental treatments on individual's QoL.
Measured: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in central spinal fluid (CSF) neurofilament light (NfL) chain levels
CSF NfL chain levels correlate with disease progression. Levels in individuals living with MND are 5 to 10-fold higher than those of healthy individuals (pg/ml)
Measured: From Baseline to End of Treatment, up to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2023
- Study start13 Feb 2024
- Primary completion30 May 2025
- Study completion30 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Motor Neuron DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open Label Extension
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurizon Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Calvary Health Care Bethlehem, Macquarie University, Australia
- Responsible party
- Sponsor
- Investigators
- Susan Mathers, BSc, MB ChB, MRCP(UK), FRACP, Principal investigator, Calvary Health Care BethlehemDominic Rowe, AM, BSc(Med), MBBS(Hons), PhD, Principal investigator, Macquarie University, Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06177431
- Sponsor's protocol ID
- MON-2023-001
- Status last verified
- May 2025
- First submitted
- 11 Dec 2023
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Extension Study to Investigate the Long Term Safety, Tolerability And Efficacy of Oral Monepantel in Individuals With Motor Neurone Disease Who Previously Completed Study MON-2021-001
- ClinicalTrials.gov ID
- NCT06177431
- Acronym / sponsor ID
- MON-2023-001
- Conditions
- Motor Neuron Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Neurizon Therapeutics LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Calvary Health Care Bethlehem, Macquarie University, Australia
- Study start
- 13 Feb 2024 (actual)
- Primary completion
- 30 May 2025 (actual)
- Study completion
- 30 May 2025 (actual)
- First posted
- 20 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicenter, 12-month open label extension study, following Phase 1 Study MON-2021-001, with a single dose of monepantel (MPL) once daily (QD) for the treatment of individuals with MND.
Detailed description
ALS/MND is a progressive, fatal neurodegenerative disease; characterized by motor neuron loss resulting in muscle weakness and atrophy, disability, and eventually death from failure of the ventilatory muscles. The median age of onset is 55 years and average survival is 3-5 years after onset of the first symptoms. The only FDA-approved disease modifying medications confer only a modest survival benefit. Given the poor prognosis and dearth of effective treatments, clinical studies are of primary importance for people with ALS/MND.
Abnormal protein accumulation within motor neurons of the brain associates with the cause of ALS/MND. Inhibition of the mTOR signaling pathway slows disease progression in certain preclinical models of ALS/MND and is suggested to provide synergy with the ALS/MND standard-of-care drug, riluzole. PharmAust has shown that MPL and its major metabolite MPL sulfone (MPLS) have activity against mTOR signaling pathways in humans; based on published data, the inhibition of mTOR may be relevant to the treatment of ALS/MND.
This Phase I Open Label Extension will further test the hypotheses that MPL administration to individuals living with ALS/MND will safely reduce disease associated protein accumulation in motor neurons and provide therapeutic benefit. The safety and tolerability of oral monepantel administration and markers of efficacy will continue to be tested in the same participants that completed the Phase I Study (MON-2021-001).
A daily dose of 10 mg/kg monepantel (QD) will be studied in the Open Label Extension Study (MON-2023-001) to further evaluate long-term safety and efficacy in participants with MND/ALS that completed the Phase I Study (MON-2021-001). Based on the previous pre-clinical efficacy data and clinical safety data, a dose of 10 mg/kg QD is estimated to produce the most robust mTOR inhibition while still being well tolerated. The 10 mg/kg QD dose was the maximum dose evaluated in the Phase 1 Study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open Label Extension
| Arm | Type | Receives |
|---|---|---|
| Monepantel treatment arm | Experimental | Drug: MonepantelDaily dose of 10 mg/kg body weight (QD) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Signed informed consent obtained prior to initiation of any study specific procedures and treatment.
- Individuals who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Able to swallow study drug tablets.
- Individuals must have completed Study MON-2021-001 and, in the opinion of the investigator, have been compliant with the study procedures and study treatment.
- Diagnosis of ALS/MND defined as clinically possible, probable, or definite according to Awaji-shima Consensus Recommendations.
Key exclusion criteria (7 listed)
- Inability to swallow oral medications or presence of a gastrointestinal disorder (e.g., malabsorption) deemed to jeopardize intestinal absorption of study drug.
- Participated in another investigational drug research study within 4 weeks (28 days) of the Baseline Visit or five half-lives of the drug, whichever is longer.
- Any other significant illness or condition that in the opinion of the study investigator would interfere with the study conduct.
- Dementia that may affect either outcome measures or subject understanding and/or compliance with study requirements and procedures.
- Women and men of childbearing potential not using effective contraception while on study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MonepantelMonepantel is provided to individuals living with ALS/MND as a white oval tablet to be administered once a day following meals | Drug | Monepantel treatment arm |
Primary outcome
Long-term safety and tolerability
Time frame: From Baseline to End of Treatment, up to 12 months.
Assess long-term safety and tolerability of 10 mg/kg body weight (BW) once daily (QD) of monepantel in individuals with Motor Neurone Disease (MND)
7 secondary outcomes
Treatment-related changes in serum neurofilament light (NfL) chain levels
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in urinary p75 levels
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes on the ALS Functional Rating Scale (ALSFRS)
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes on the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS)
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in slow vital capacity (in participants with the capacity to undergo testing)
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in Quality of Life (QOL) Assessment: ALSSQOL-R
Time frame: From Baseline to End of Treatment, up to 12 months.
Treatment-related changes in central spinal fluid (CSF) neurofilament light (NfL) chain levels
Time frame: From Baseline to End of Treatment, up to 12 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Mathers, BSc, MB ChB, MRCP(UK), FRACP principal investigator
Calvary Health Care Bethlehem
Dominic Rowe, AM, BSc(Med), MBBS(Hons), PhD principal investigator
Macquarie University, Sydney
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Monepantel in people with Motor Neuron Disease, run by Neurizon Therapeutics Limited at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Long-term safety and tolerability (time frame: From Baseline to End of Treatment, up to 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.